1. Rodriguez de Fonseca, F., del Arco, I, Bermudez-Silva, F. J., Bilbao, A. and others. (2005). The endocannabinoid system: physiology and pharmacology. Alcohol Alcohol. 40: 2-14.
2. Serrano, A. and Parsons, L. H. (2011). Endocannabinoid influence in drug reinforcement, dependence and addictionrelated behaviors. Pharmacol.Ther. 132: 215-241.
3. Maccarrone, M., Gasperi, V., Catani, M. V., Diep, T. A. and others. (2010). The endocannabinoid system and its relevance for nutrition. Annu.Rev.Nutr. 30: 423-440.
4. Aggarwal, S. K. (2012). Cannabinergic Pain Medicine: A Concise Clinical Primer and Survey of Randomizedcontrolled Trial Results. Clin.J.Pain. 29: 162-171.
5. Bradshaw, H. B. and Walker, J. M. (2005). The expanding field of cannabimimetic and related lipid mediators. Br.J.Pharmacol. 144: 459-465.
6. De Petrocellis, L. and Di Marzo, V. (2009). An introduction to the endocannabinoid system: from the early to the latest concepts. Best.Pract.Res.Clin.Endocrinol.Metab. 23: 1-15.
7. De Petrocellis, L. and Di, Marzo, V. (2010). Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: focus on G-protein-coupled receptors and transient receptor potential channels. J.Neuroimmune.Pharmacol. 5: 103-121.
8. O’Sullivan, S. E. and Kendall, D. A. (2010). Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology. 215: 611-616.
9. Hansen, H. S. (2010). Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain. Exp.Neurol. 224: 48-55.
10. Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T. and others. (1998). An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur.J.Pharmacol. 353: 23-31.
11. Quarta, C., Mazza, R., Obici, S., Pasquali, R. and others. (2011). Energy balance regulation by endocannabinoids at central and peripheral levels. Trends Mol.Med. 17: 518-526.
12. Battista, N., Di, Tommaso M., Bari, M., and Maccarrone, M. (2012). The endocannabinoid system: an overview. Front.Behav.Neurosci. 6: 9-
13. Horvath, B., Mukhopadhyay, P., Hasko, G., and Pacher, P. (2012). The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications. Am.J.Pathol. 180: 432-442.
14. Hermanson, D. J. and Marnett, L. J. (2011). Cannabinoids, endocannabinoids, and cancer. Cancer Metastasis Rev. 30: 599-612.
15. Rouzer, C. A. and Marnett, L. J. (2011). Endocannabinoid oxygenation by cyclooxygenases, lipoxygenases, and cytochromes P450: cross-talk between the eicosanoid and endocannabinoid signaling pathways. Chem.Rev. 111: 5899-5921.
16. Pertwee, R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br.J.Pharmacol. 153: 199-215.
17. Di Marzo, V., Piscitelli, F., and Mechoulam, R. (2011). Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. Handb.Exp.Pharmacol. 75-104.
18. Bab, I. and Zimmer, A. (2008). Cannabinoid receptors and the regulation of bone mass. Br.J.Pharmacol. 153: 182188.
19. Howlett, A. C., Barth, F., Bonner, T. I., Cabral, G. and others. (2002). International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol.Rev. 54: 161-202.
20. Pertwee, R. G., Howlett, A. C., Abood, M. E., Alexander, S. P. and others. (2010). International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB and CB. Pharmacol.Rev. 62: 588-631.
21. Kraft, B. (2012). Is there any clinically relevant cannabinoid-induced analgesia? Pharmacology. 89: 237-246.
22. Guindon, J. and Hohmann, A. G. (2009). The endocannabinoid system and pain. CNS.Neurol.Disord Drug Targets. 8: 403-421.
23. Teixeira, D., Pestana, D., Faria, A., Calhau, C. and others. (2010). Modulation of adipocyte biology by delta(9)tetrahydrocannabinol. Obesity.(Silver.Spring). 18: 2077-2085.
24. Greineisen, W. E. and Turner, H. (2010). Immunoactive effects of cannabinoids: considerations for the therapeutic use of cannabinoid receptor agonists and antagonists. Int.Immunopharmacol. 10: 547-555.
25. Jean-Gilles, L., Gran, B., and Constantinescu, C. S. (2010). Interaction between cytokines, cannabinoids and the nervous system. Immunobiology. 215: 606-610.
26. Rice, W., Shannon, J. M., Burton, F., and Fiedeldey, D. (1997). Expression of a brain-type cannabinoid receptor (CB1) in alveolar Type II cells in the lung: regulation by hydrocortisone. Eur.J.Pharmacol. 327: 227-232.
27. Shmist, Y. A., Goncharov, I., Eichler, M., Shneyvays, V. and others. (2006). Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production. Mol.Cell Biochem. 283: 75-83.
28. Wright, K., Rooney, N., Feeney, M., Tate, J. and others. (2005). Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology. 129: 437-453.
29. Marquez, L., Suarez, J., Iglesias, M., Bermudez-Silva, F. J. and others. (2009). Ulcerative colitis induces changes on the expression of the endocannabinoid system in the human colonic tissue. PLoS.One. 4: e6893.-
30. Linari, G., Agostini, S., Amadoro, G., Ciotti, M. T. and others. (2009). Involvement of cannabinoid CB1- and CB2receptors in the modulation of exocrine pancreatic secretion. Pharmacol.Res. 59: 207-214.
31. Izzo, A. A. and Sharkey, K. A. (2010). Cannabinoids and the gut: new developments and emerging concepts. Pharmacol.Ther. 126: 21-38.
32. Purohit, V., Rapaka, R., and Shurtleff, D. (2010). Role of cannabinoids in the development of fatty liver (steatosis). AAPS.J. 12: 233-237.
33. Mallat, A., Teixeira-Clerc, F., Deveaux, V., Manin, S. and others. (2011). The endocannabinoid system as a key mediator during liver diseases: new insights and therapeutic openings. Br.J.Pharmacol. 163: 1432-1440.
34. Jenkin, K. A., McAinch, A. J., Grinfeld, E., and Hryciw, D. H. (2010). Role for cannabinoid receptors in human proximal tubular hypertrophy. Cell Physiol Biochem. 26: 879-886.
35. Gratzke, C., Streng, T., Park, A., Christ, G. and others. (2009). Distribution and function of cannabinoid receptors 1 and 2 in the rat, monkey and human bladder. J.Urol. 181: 1939-1948.
36. Tyagi, P., Tyagi, V., Yoshimura, N., and Chancellor, M. (2010). Functional role of cannabinoid receptors in urinary bladder. Indian J.Urol. 26: 26-35.
37. Karasu, T., Marczylo, T. H., Maccarrone, M., and Konje, J. C. (2011). The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility. Hum.Reprod.Update. 17: 347-361.
38. Idris, A. I. and Ralston, S. H. (2010). Cannabinoids and bone: friend or foe? Calcif.Tissue Int. 87: 285-297.
39. Watkins, B. A., Hutchins, H., Li, Y., and Seifert, M. F. (2010). The endocannabinoid signaling system: a marriage of PUFA and musculoskeletal health. J.Nutr.Biochem. 21: 1141-1152.
40. Richardson, D., Pearson, R. G., Kurian, N., Latif, M. L. and others. (2008). Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res.Ther. 10: R43.-
41. Biro, T., Toth, B. I., Hasko, G., Paus, R. and others. (2009). The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol.Sci. 30: 411-420.
42. Mackie, K. (2008). Signaling via CNS cannabinoid receptors. Mol.Cell Endocrinol. 286: S60-S65.
43. Cabral, G. A. Marihuana and the immune system. Marihuana and medicine. Nahas, G. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa: Humana Press, 1999.
44. De Petrocellis, L., Ligresti, A., Moriello, A. S., Allara, M. and others. (2011). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br.J.Pharmacol. 163: 1479-1494.
45. Alger, B. E. (2004). Endocannabinoids: getting the message across. Proc.Natl.Acad.Sci.U.S.A. 101: 8512-8513.
46. Bisogno, T. (2008). Endogenous cannabinoids: structure and metabolism. J.Neuroendocrinol. 20 Suppl 1: 1-9.
47. Miller, L. K. and Devi, L. A. (2011). The highs and lows of cannabinoid receptor expression in disease: mechanisms and their therapeutic implications. Pharmacol.Rev. 63: 461-470.
48. Martin-Sanchez, E., Furukawa, T. A., Taylor, J., and Martin, J. L. (2009). Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 10: 1353-1368.
49. Gowran, A., Noonan, J., and Campbell, V. A. (2011). The multiplicity of action of cannabinoids: implications for treating neurodegeneration. CNS.Neurosci.Ther. 17: 637-644.
50. Guindon, J., Lai, Y., Takacs, S. M., Bradshaw, H. B. and others. (2012). Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: Effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment. Pharmacol.Res. 67: 94-109.
51. Russo, E. B. and Hohmann, A. G. Role of cannabinoids in pain management. Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Behavioral Approaches: The AMERICAN ACADEMY OF PAIN MEDICINE Textbook on Patient Management . Deer, T. R. and Leong, M. S. New York: Springer, 2012.
52. Guzman, M. (2003). Cannabinoids: potential anticancer agents. Nat.Rev.Cancer. 3: 745-755.
53. Di Marzo, V, Bifulco, M., and De Petrocellis, L. (2004). The endocannabinoid system and its therapeutic exploitation. Nat.Rev.Drug Discov. 3: 771-784.
54. Bazzaz, F. A., Dusek, D., Seigler, D. S., and Haney, A. W. (1975). Photosynthesis and cannabinoid content of temperate and tropical populations of Cannabis sativa. Biochemical Systematics and Ecology. 3: 15-18.
55. Elsohly, M. A. and Slade, D. (2005). Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci. 78: 539-548.
56. Zhu, H. J., Wang, J. S., Markowitz, J. S., Donovan, J. L. and others. (2006). Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J.Pharmacol.Exp.Ther. 317: 850-857.
57. Balducci, C., Nervegna, G., and Cecinato, A. (2009). Evaluation of principal cannabinoids in airborne particulates. Anal.Chim.Acta. 641: 89-94.
58. Yamaori, S., Kushihara, M., Yamamoto, I., and Watanabe, K. (2010). Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem.Pharmacol. 79: 1691-1698.
59. Hillig, K. W. and Mahlberg, P. G. (2004). A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae). Am.J.Bot. 91: 966-975.
60. Mehmedic, Z., Chandra, S., Slade, D., Denham, H. and others. (2010). Potency Trends of Delta(9)-THC and Other Cannabinoids in Confiscated Cannabis Preparations from 1993 to 2008*. J.Forensic Sci. 55: 1209-1217.
61. Whittle, B. A. and Guy, G. W. Development of cannabis-based medicines: risk, benefit and serendipity. The Medicinal Uses of Cannabis and Cannabinoids. Guy, G. W., Whittle, B. A., and Robson, P. J. London: Pharmaceutical Press, 2004.
62. Huestis, M. A. (2007). Human cannabinoid pharmacokinetics. Chem.Biodivers. 4: 1770-1804.
63. Dussy, F. E., Hamberg, C., Luginbuhl, M., Schwerzmann, T. and others. (2005). Isolation of Delta9-THCA-A from hemp and analytical aspects concerning the determination of Delta9-THC in cannabis products. Forensic Sci.Int. 149: 3-10.
64. Ashton, C. H. (2001). Pharmacology and effects of cannabis: a brief review. Br.J.Psychiatry. 178: 101-106.
65. Health Canada. Product Information Sheet on Dried Marihuana (Cannabis). 2008.
66. Health Canada. Product information sheet on dried marihuana (Cannabis spp.). Health Canada website. Health Canada. 2005.
67. Fischedick, J., Van der Kooy, F., and Verpoorte, R. (2010). Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor. Chem.Pharm.Bull.(Tokyo). 58: 201-207.
68. Maertens, R. M., White, P. A., Rickert, W., Levasseur, G. and others. (2009). The genotoxicity of mainstream and sidestream marijuana and tobacco smoke condensates. Chem.Res.Toxicol. 22: 1406-1414.
69. International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans: Tobacco smoke and involuntary smoking. 2004.
70. Moir, D., Rickert, W. S., Levasseur, G., Larose, Y. and others. (2008). A comparison of mainstream and sidestream marijuana and tobacco cigarette smoke produced under two smoking conditions. Chem.Res.Toxicol. 21: 494-502.
71. Russo, E. B. and McPartland, J. M. (2003). Cannabis is more than simply delta(9)-tetrahydrocannabinol. Psychopharmacology (Berl). 165: 431-432.
72. Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br.J.Pharmacol. 163: 1344-1364.
73. Baker, P. B., Taylor, B. J., and Gough, T. A. (1981). The tetrahydrocannabinol and tetrahydrocannabinolic acid content of cannabis products. J.Pharm.Pharmacol. 33: 369-372.
74. Garrett, E. R. and Hunt, C. A. (1974). Physiochemical properties, solubility, and protein binding of delta9tetrahydrocannabinol. J.Pharm.Sci. 63: 1056-1064.
75. Fairbairn, J. W., Liebmann, J. A., and Rowan, M. G. (1976). The stability of Cannabis and its preparations on storage. J.Pharm.Pharmacol. 28: 1-7.
76. Thomas, B. F., Parker, V. L., Caddell, L. W., Jones, L. V. and others. Composition and stability of a standard marihuana cigarette. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
77. Govaerts, S. J., Hermans, E., and Lambert, D. M. (2004). Comparison of cannabinoid ligands affinities and efficacies in murine tissues and in transfected cells expressing human recombinant cannabinoid receptors. Eur.J.Pharm.Sci. 23: 233-243.
78. Pertwee, R. G. (2010). Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr.Med.Chem. 17: 1360-1381.
79. Hajos, N., Ledent, C., and Freund, T. F. (2001). Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience. 106: 1-4.
80. Darmani, N. A., Janoyan, J. J., Crim, J., and Ramirez, J. (2007). Receptor mechanism and antiemetic activity of structurally-diverse cannabinoids against radiation-induced emesis in the least shrew. Eur.J.Pharmacol. 563: 187-196.
81. Abrahamov, A., Abrahamov, A., and Mechoulam, R. (1995). An efficient new cannabinoid antiemetic in pediatric oncology. Life Sci. 56: 2097-2102.
82. Izzo, A. A., Borrelli, F., Capasso, R., Di, Marzo, V and others. (2009). Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol.Sci. 30: 515-527.
83. Institute of Medicine. Cannabinoids and animal physiology. Marijuana and medicine: Assessing the science base. Joy, J. E., Watson, S. J., and Benson, J. A. Washington, DC: National Academy Press, 1999.
84. Musty, R. E. Natural cannabinoids: interactions and effects. The medicinal uses of cannabis and cannabinoids. Guy, G. W, Whittle, B. A., and Robson, P. J. London: Pharmaceutical Press, 2004.
85. Ruhaak, L. R., Felth, J., Karlsson, P. C., Rafter, J. J. and others. (2011). Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol.Pharm.Bull. 34: 774-778.
86. Cascio, M. G., Gauson, L. A., Stevenson, L. A., Ross, R. A. and others. (2010). Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br.J.Pharmacol. 159: 129-141.
87. Brown, A. J. (2007). Novel cannabinoid receptors. Br.J.Pharmacol. 152: 567-575.
88. Parker, L. A., Rock, E., and Limebeer, C. (2010). Regulation of nausea and vomiting by cannabinoids. Br.J.Pharmacol. 163: 1411-1422.
89. Thomas, A., Stevenson, L. A., Wease, K. N., Price, M. R. and others. (2005). Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. Br.J.Pharmacol. 146: 917-926.
90. Bolognini, D., Costa, B., Maione, S., Comelli, F. and others. (2010). The plant cannabinoid Delta9tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. Br.J.Pharmacol. 160: 677-687.
91. Hill, A. J., Weston, S. E., Jones, N. A., Smith, I. and others. (2010). Delta-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. Epilepsia. 51: 1522-1532.
92. Riedel, G., Fadda, P., McKillop-Smith, S., Pertwee, R. G. and others. (2009). Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. Br.J.Pharmacol. 156: 1154-1166.
93. Pertwee, R. G. (2005). Pharmacological actions of cannabinoids. Handb.Exp.Pharmacol. 1-51.
94. Jones, G. and Pertwee, R. G. (1972). A metabolic interaction in vivo between cannabidiol and 1 tetrahydrocannabinol. Br.J.Pharmacol. 45: 375-377.
95. Karniol, I. G., Shirakawa, I., Kasinski, N., Pfeferman, A. and others. (1974). Cannabidiol interferes with the effects of delta 9 – tetrahydrocannabinol in man. Eur.J.Pharmacol. 28: 172-177.
96. Zuardi, A. W., Finkelfarb, E., Bueno, O. F., Musty, R. E. and others. (1981). Characteristics of the stimulus produced by the mixture of cannabidiol with delta 9-tetrahydrocannabinol. Arch.Int.Pharmacodyn.Ther. 249: 137146.
97. Zuardi, A. W., Shirakawa, I., Finkelfarb, E., and Karniol, I. G. (1982). Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 76: 245-250.
98. Zuardi, A. W. and Karniol, I. G. (1983). Effects on variable-interval performance in rats of delta 9tetrahydrocannabinol and cannabidiol, separately and in combination. Braz.J.Med.Biol.Res. 16: 141-146.
99. Reid, M. J. and Bornheim, L. M. (2001). Cannabinoid-induced alterations in brain disposition of drugs of abuse. Biochem.Pharmacol. 61: 1357-1367.
100. Fadda, P., Robinson, L., Fratta, W., Pertwee, R. G. and others. (2004). Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats. Neuropharmacology. 47: 1170-1179.
101. Ilan, A. B., Gevins, A., Coleman, M., Elsohly, M. A. and others. (2005). Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids. Behav.Pharmacol. 16: 487-496.
102. Nadulski, T., Pragst, F., Weinberg, G., Roser, P. and others. (2005). Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC versus standardized cannabis extract. Ther.Drug Monit. 27: 799-810.
103. Varvel, S. A., Wiley, J. L., Yang, R., Bridgen, D. T. and others. (2006). Interactions between THC and cannabidiol in mouse models of cannabinoid activity. Psychopharmacology (Berl). 186: 226-234.
104. Fusar-Poli, P., Crippa, J. A., Bhattacharyya, S., Borgwardt, S. J. and others. (2009). Distinct effects of {delta}9tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch.Gen.Psychiatry. 66: 95-105.
105. Bhattacharyya, S., Morrison, P. D., Fusar-Poli, P., Martin-Santos, R. and others. (2010). Opposite effects of delta-9tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 35: 764-774.
106. Winton-Brown, T. T., Allen, P., Bhattacharyya, S., Borgwardt, S. J. and others. (2011). Modulation of auditory and visual processing by delta-9-tetrahydrocannabinol and cannabidiol: an FMRI study. Neuropsychopharmacology. 36: 1340-1348.
107. Karschner, E. L., Darwin, W. D., McMahon, R. P., Liu, F. and others. (2011). Subjective and physiological effects after controlled Sativex and oral THC administration. Clin.Pharmacol.Ther. 89: 400-407.
108. Karschner, E. L., Darwin, W. D., Goodwin, R. S., Wright, S. and others. (2011). Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin.Chem. 57: 66-75.
109. Zuardi, A. W., Hallak, J. E., and Crippa, J. A. (2012). Interaction between cannabidiol (CBD) and (9)tetrahydrocannabinol (THC): influence of administration interval and dose ratio between the cannabinoids. Psychopharmacology (Berl). 219: 247-249.
110. Klein, C., Karanges, E., Spiro, A., Wong, A. and others. (2011). Cannabidiol potentiates Delta(9)tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. Psychopharmacology (Berl). 218: 443-457.
111. Wachtel, S. R., Elsohly, M. A., Ross, S. A., Ambre, J. and others. (2002). Comparison of the subjective effects of Delta(9)-tetrahydrocannabinol and marijuana in humans. Psychopharmacology (Berl). 161: 331-339.
112. Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D. and others. (2010). Multicenter, doubleblind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J.Pain Symptom.Manage. 39: 167-179.
113. Schubart, C. D., Sommer, I. E., van Gastel, W. A., Goetgebuer, R. L. and others. (2011). Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr.Res. 130: 216-221.
114. Kumar, R. N., Chambers, W. A., and Pertwee, R. G. (2001). Pharmacological actions and therapeutic uses of cannabis and cannabinoids. Anaesthesia. 56: 1059-1068.
115. British Medical Association. Therapeutic uses of cannabis. Amsterdam: Harwood Academic Publishers, 1997.
116. Hill, M. N., Froese, L. M., Morrish, A. C., Sun, J. C. and others. (2006). Alterations in behavioral flexibility by cannabinoid CB1 receptor agonists and antagonists. Psychopharmacology (Berl). 187: 245-259.
117. Zuurman, L., Ippel, A. E., Moin, E., and van Gerven, J. M. (2009). Biomarkers for the effects of cannabis and THC in healthy volunteers. Br.J.Clin.Pharmacol. 67: 5-21.
118. Institute of Medicine. First, do no harm: consequences of marijuana use and abuse. Marijuana and medicine: Assessing the science base. Joy, J. E., Watson, S. J., and Benson, J. A. Washington, DC: National Academy Press, 1999.
119. Beaconsfield, P., Ginsburg, J., and Rainsbury, R. (1972). Marihuana smoking. Cardiovascular effects in man and possible mechanisms. N.Engl.J.Med. 287: 209-212.
120. Perez-Reyes, M. (1990). Marijuana smoking: factors that influence the bioavailability of tetrahydrocannabinol. NIDA Res.Monogr. 99: 42-62.
121. Aryana, A. and Williams, M. A. (2007). Marijuana as a trigger of cardiovascular events: speculation or scientific certainty? Int.J.Cardiol. 118: 141-144.
122. Hall, W. and Solowij, N. (1998). Adverse effects of cannabis. Lancet. 352: 1611-1616.
123. Ameri, A. (1999). The effects of cannabinoids on the brain. Prog.Neurobiol. 58: 315-348.
124. Barnett, G., Licko, V., and Thompson, T. (1985). Behavioral pharmacokinetics of marijuana. Psychopharmacology (Berl). 85: 51-56.
125. Kelly, T. H., Foltin, R. W., and Fischman, M. W. (1993). Effects of smoked marijuana on heart rate, drug ratings and task performance by humans. Behav.Pharmacol. 4: 167-178.
126. Fant, R. V., Heishman, S. J., Bunker, E. B., and Pickworth, W. B. (1998). Acute and residual effects of marijuana in humans. Pharmacol.Biochem.Behav. 60: 777-784.
127. Hollister, L. E. (1998). Health aspects of cannabis: revisited. Int.J.Neuropsychopharmacol. 1: 71-80.
128. Miller, L. L. Marihuana: Acute effects on human memory. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
129. Hart, C. L., Ilan, A. B., Gevins, A., Gunderson, E. W. and others. (2010). Neurophysiological and cognitive effects of smoked marijuana in frequent users. Pharmacol.Biochem.Behav. 96: 333-341.
130. Crean, R. D., Crane, N. A., and Mason, B. J. (2011). An Evidence Based Review of Acute and Long-Term Effects of Cannabis Use on Executive Cognitive Functions. J.Addict.Med. 5: 1-8.
131. Heishman, S. J., Huestis, M. A., Henningfield, J. E., and Cone, E. J. (1990). Acute and residual effects of marijuana: profiles of plasma THC levels, physiological, subjective, and performance measures. Pharmacol.Biochem.Behav. 37: 561-565.
132. Curran, H. V., Brignell, C., Fletcher, S., Middleton, P. and others. (2002). Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology (Berl). 164: 61-70.
133. Ramaekers, J. G., Moeller, M. R., van, Ruitenbeek P., Theunissen, E. L. and others. (2006). Cognition and motor control as a function of Delta9-THC concentration in serum and oral fluid: limits of impairment. Drug Alcohol Depend. 85: 114-122.
134. O’Kane, C. J., Tutt, D. C., and Bauer, L. A. (2002). Cannabis and driving: a new perspective. Emerg.Med.(Fremantle.). 14: 296-303.
135. Hansteen, R. W., Miller, R. D., Lonero, L., Reid, L. D. and others. (1976). Effects of cannabis and alcohol on automobile driving and psychomotor tracking. Ann.N.Y.Acad.Sci. 282: 240-256.
136. Leirer, V. O., Yesavage, J. A., and Morrow, D. G. (1991). Marijuana carry-over effects on aircraft pilot performance. Aviat.Space Environ.Med. 62: 221-227.
137. Smiley, A. Marijuana: On-road and driving-simulator studies. The Health Effects of Cannabis. Kalant, H., Corrigall, W., Hall, W., and Smart, R. Toronto, Canada: Centre of Addiction and Mental Health, 1999.
138. van Os, J., Bak, M., Hanssen, M., Bijl, R. V. and others. (2002). Cannabis use and psychosis: a longitudinal population-based study. Am.J.Epidemiol. 156: 319-327.
139. D’Souza, D. C., Abi-Saab, W. M., Madonick, S., Forselius-Bielen, K. and others. (2005). Delta-9tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol.Psychiatry. 57: 594-608.
140. D’Souza, D. C., Perry, E., MacDougall, L., Ammerman, Y. and others. (2004). The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology. 29: 1558-1572.
141. Moore, T. H., Zammit, S., Lingford-Hughes, A., Barnes, T. R. and others. (2007). Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 370: 319-328.
142. Abrams, D. I., Jay, C. A., Shade, S. B., Vizoso, H. and others. (2007). Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 68: 515-521.
143. Henquet, C., van, Os J., Kuepper, R., Delespaul, P. and others. (2010). Psychosis reactivity to cannabis use in daily life: an experience sampling study. Br.J.Psychiatry. 196: 447-453.
144. Korver, N., Nieman, D. H., Becker, H. E., van de Fliert, J. R. and others. (2010). Symptomatology and neuropsychological functioning in cannabis using subjects at ultra-high risk for developing psychosis and healthy controls. Aust.N.Z.J.Psychiatry. 44: 230-236.
145. Favrat, B., Menetrey, A., Augsburger, M., Rothuizen, L. E. and others. (2005). Two cases of “cannabis acute psychosis” following the administration of oral cannabis. BMC.Psychiatry. 5: 17-22.
146. Henquet, C., Krabbendam, L., Spauwen, J., Kaplan, C. and others. (2005). Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ. 330: 11-15.
147. Crippa, J. A., Zuardi, A. W., Martin-Santos, R., Bhattacharyya, S. and others. (2009). Cannabis and anxiety: a critical review of the evidence. Hum.Psychopharmacol. 24: 515-523.
148. van Rossum, I, Boomsma, M., Tenback, D., Reed, C. and others. (2009). Does cannabis use affect treatment outcome in bipolar disorder? A longitudinal analysis. J.Nerv.Ment.Dis. 197: 35-40.
149. Ongur, D., Lin, L., and Cohen, B. M. (2009). Clinical characteristics influencing age at onset in psychotic disorders. Compr.Psychiatry. 50: 13-19.
150. De Hert, M., Wampers, M., Jendricko, T., Franic, T. and others. (2011). Effects of cannabis use on age at onset in schizophrenia and bipolar disorder. Schizophr.Res. 126: 270-276.
151. Harder, S. and Rietbrock, S. (1997). Concentration-effect relationship of delta-9-tetrahydrocannabiol and prediction of psychotropic effects after smoking marijuana. Int.J.Clin.Pharmacol.Ther. 35: 155-159.
152. Johns, A. (2001). Psychiatric effects of cannabis. Br.J.Psychiatry. 178: 116-122.
153. Boyce, A. and McArdle, P. (2007). Long-term effects of cannabis. Pediatrics and child health. 18: 37-41.
154. Zammit, S., Moore, T. H., Lingford-Hughes, A., Barnes, T. R. and others. (2008). Effects of cannabis use on outcomes of psychotic disorders: systematic review. Br.J.Psychiatry. 193: 357-363.
155. Moreira, F. A., Grieb, M., and Lutz, B. (2009). Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: focus on anxiety and depression. Best.Pract.Res.Clin.Endocrinol.Metab. 23: 133144.
156. Vandrey, R. and Haney, M. (2009). Pharmacotherapy for cannabis dependence: how close are we? CNS.Drugs. 23: 543-553.
157. Lal, S., Prasad, N., Ryan, M., Tangri, S. and others. (2011). Cannabis use amongst patients with inflammatory bowel disease. Eur.J.Gastroenterol.Hepatol. 23: 891-896.
158. Fiz, J., Duran, M., Capella, D., Carbonell, J. and others. (2011). Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life. PLoS.One. 6: e18440.-
159. Tramer, M. R., Carroll, D., Campbell, F. A., Reynolds, D. J. and others. (2001). Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 323: 16-21.
160. Corcoran, C. M., Kimhy, D., Stanford, A., Khan, S. and others. (2008). Temporal association of cannabis use with symptoms in individuals at clinical high risk for psychosis. Schizophr.Res. 106: 286-293.
161. Schierenbeck, T., Riemann, D., Berger, M., and Hornyak, M. (2008). Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana. Sleep Med.Rev. 12: 381-389.
162. Hunault, C. C., Mensinga, T. T., Bocker, K. B., Schipper, C. M. and others. (2009). Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9tetrahydrocannabinol (THC). Psychopharmacology (Berl). 204: 85-94.
163. Scott, J., Martin, G., Bor, W., Sawyer, M. and others. (2009). The prevalence and correlates of hallucinations in Australian adolescents: results from a national survey. Schizophr.Res. 107: 179-185.
164. Page, S. A., Verhoef, M. J., Stebbins, R. A., Metz, L. M. and others. (2003). Cannabis use as described by people with multiple sclerosis. Can.J.Neurol.Sci. 30: 201-205.
165. Clark, A. J., Ware, M. A., Yazer, E., Murray, T. J. and others. (2004). Patterns of cannabis use among patients with multiple sclerosis. Neurology. 62: 2098-2100.
166. Haney, M., Rabkin, J., Gunderson, E., and Foltin, R. W. (2005). Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood. Psychopharmacology (Berl). 181: 170-178.
167. Haney, M., Gunderson, E. W., Rabkin, J., Hart, C. L. and others. (2007). Dronabinol and marijuana in HIV-positive marijuana smokers. Caloric intake, mood, and sleep. J.Acquir.Immune.Defic.Syndr. 45: 545-554.
168. Wilsey, B., Marcotte, T., Tsodikov, A., Millman, J. and others. (2008). A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J.Pain. 9: 506-521.
169. Sewell, R. A., Poling, J., and Sofuoglu, M. (2009). The effect of cannabis compared with alcohol on driving. Am.J.Addict. 18: 185-193.
170. Bramness, J. G., Khiabani, H. Z., and Morland, J. (2010). Impairment due to cannabis and ethanol: clinical signs and additive effects. Addiction. 105: 1080-1087.
171. Ronen, A., Chassidim, H. S., Gershon, P., Parmet, Y. and others. (2010). The effect of alcohol, THC and their combination on perceived effects, willingness to drive and performance of driving and non-driving tasks. Accid.Anal.Prev. 42: 1855-1865.
172. Ware, M. A., Wang, T., Shapiro, S., Robinson, A. and others. (2010). Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 182: E694-E701.
173. Lynch, M. E. and Campbell, F. (2011). Cannabinoids for Treatment of Chronic Non-Cancer Pain; a Systematic Review of Randomized Trials. Br.J.Clin.Pharmacol. 72: 735-744.
174. Abbott Products Inc. Marinol Product Monograph. 2010.
175. Asbridge, M., Hayden, J. A., and Cartwright, J. L. (2012). Acute cannabis consumption and motor vehicle collision risk: systematic review of observational studies and meta-analysis. BMJ. 344: e536-
176. Downey, L. A., King, R., Papafotiou, K., Swann, P. and others. (2012). The effects of cannabis and alcohol on simulated driving: Influences of dose and experience. Accid.Anal.Prev. 50: 879-886.
177. Elvik, R. (2012). Risk of road accident associated with the use of drugs: A systematic review and meta-analysis of evidence from epidemiological studies (in press). Accid.Anal.Prev.
178. Honarmand, K., Tierney, M. C., O’Connor, P., and Feinstein, A. (2011). Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurology. 76: 1153-1160.
179. Pope, H. G., Jr., Gruber, A. J., Hudson, J. I., Huestis, M. A. and others. (2002). Cognitive measures in long-term cannabis users. J.Clin.Pharmacol. 42: 41S-47S.
180. Solowij, N., Stephens, R. S., Roffman, R. A., Babor, T. and others. (2002). Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA. 287: 1123-1131.
181. Ilan, A. B., Smith, M. E., and Gevins, A. (2004). Effects of marijuana on neurophysiological signals of working and episodic memory. Psychopharmacology (Berl). 176: 214-222.
182. Williamson, E. M. and Evans, F. J. (2000). Cannabinoids in clinical practice. Drugs. 60: 1303-1314.
183. Weinstein, A., Brickner, O., Lerman, H., Greemland, M. and others. (2008). Brain imaging study of the acute effects of Delta9-tetrahydrocannabinol (THC) on attention and motor coordination in regular users of marijuana. Psychopharmacology (Berl). 196: 119-131.
184. Greenwald, M. K. and Stitzer, M. L. (2000). Antinociceptive, subjective and behavioral effects of smoked marijuana in humans. Drug Alcohol Depend. 59: 261-275.
185. Wallace, M., Schulteis, G., Atkinson, J. H., Wolfson, T. and others. (2007). Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology. 107: 785-796.
186. Ellis, R. J., Toperoff, W., Vaida, F., van den Brande, G. and others. (2009). Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 34: 672-680.
187. Abrams, D. I., Couey, P., Shade, S. B., Kelly, M. E. and others. (2011). Cannabinoid-opioid interaction in chronic pain. Clin.Pharmacol.Ther. 90: 844-851.
188. Corey-Bloom, J., Wolfson, T., Gamst, A., Jin, S. and others. (2012). Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ. 184: 1143-1150.
189. Lahat, A., Lang, A., and Ben-Horin, S. (2012). Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: a pilot prospective study. Digestion. 85: 18.
190. Lynch, M. E., Young, J., and Clark, A. J. (2006). A case series of patients using medicinal marihuana for management of chronic pain under the Canadian Marihuana Medical Access Regulations. J.Pain Symptom.Manage. 32: 497-501.
191. Musty, R and Rossi, R. (2001). Effects of smoked cannabis and oral delta-9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: A review of state clinical trials. Journal of Cannabis Therapeutics. 1: 29-42.
192. Soderpalm, A. H., Schuster, A., and de, Wit H. (2001). Antiemetic efficacy of smoked marijuana: subjective and behavioral effects on nausea induced by syrup of ipecac. Pharmacol.Biochem.Behav. 69: 343-350.
193. Bedi, G., Foltin, R. W., Gunderson, E. W., Rabkin, J. and others. (2010). Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study. Psychopharmacology (Berl). 212: 675-686.
194. Sannarangappa, V. and Tan, C. (2009). Cannabinoid hyperemesis. Intern.Med.J. 39: 777-778.
195. Donnino, M. W., Cocchi, M. N., Miller, J., and Fisher, J. (2011). Cannabinoid hyperemesis: a case series. J.Emerg.Med. 40: e63-e66.
196. Sullivan, S. (2010). Cannabinoid hyperemesis. Can.J.Gastroenterol. 24: 284-285.
197. Miller, J. B., Walsh, M., Patel, P. A., Rogan, M. and others. (2010). Pediatric cannabinoid hyperemesis: two cases. Pediatr.Emerg.Care. 26: 919-920.
198. Patterson, D. A., Smith, E., Monahan, M., Medvecz, A. and others. (2010). Cannabinoid hyperemesis and compulsive bathing: a case series and paradoxical pathophysiological explanation. J.Am.Board Fam.Med. 23: 790-793.
199. Choung, R. S., Locke, G. R., III, Lee, R. M., Schleck, C. D. and others. (2012). Cyclic vomiting syndrome and functional vomiting in adults: association with cannabinoid use in males. Neurogastroenterol.Motil. 24: 206, e1.
200. Francis, H. (2011). Emerging role of chronic cannabis usage and hyperemesis syndrome. South.Med.J. 104: 665-
201. Schmid, S. M., Lapaire, O., Huang, D. J., Jurgens, F. E. and others. (2011). Cannabinoid hyperemesis syndrome: an underreported entity causing nausea and vomiting of pregnancy. Arch.Gynecol.Obstet. 284: 1095-1097.
202. Wallace, E. A., Andrews, S. E., Garmany, C. L., and Jelley, M. J. (2011). Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm. South.Med.J. 104: 659-664.
203. Simonetto, D. A., Oxentenko, A. S., Herman, M. L., and Szostek, J. H. (2012). Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin.Proc. 87: 114-119.
204. Wild, K. and Wilson, H. (2012). Cannabinoid hyperemesis. Emerg.Med.J. 29: 67-69.
205. Foltin, R. W., Fischman, M. W., and Byrne, M. F. (1988). Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory. Appetite. 11: 1-14.
206. Mattes, R. D., Engelman, K., Shaw, L. M., and Elsohly, M. A. (1994). Cannabinoids and appetite stimulation. Pharmacol.Biochem.Behav. 49: 187-195.
207. Haney, M., Ward, A. S., Comer, S. D., Foltin, R. W. and others. (1999). Abstinence symptoms following oral THC administration to humans. Psychopharmacology (Berl). 141: 385-394.
208. Sutton, I. R. and Daeninck, P. (2006). Cannabinoids in the management of intractable chemotherapy-induced nausea and vomiting and cancer-related pain. J.Support.Oncol. 4: 531-535.
209. Pisanti, S., Malfitano, A. M., Grimaldi, C., Santoro, A. and others. (2009). Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Best.Pract.Res.Clin.Endocrinol.Metab. 23: 117-131.
210. Lichtman, A. H. and Martin, B. R. (2005). Cannabinoid tolerance and dependence. Handb.Exp.Pharmacol. 691-717.
211. Gonzalez, S., Cebeira, M., and Fernandez-Ruiz, J. (2005). Cannabinoid tolerance and dependence: a review of studies in laboratory animals. Pharmacol.Biochem.Behav. 81: 300-318.
212. Jones, R. T., Benowitz, N., and Bachman, J. (1976). Clinical studies of cannabis tolerance and dependence. Ann.N.Y.Acad.Sci. 282: 221-239.
213. Compton, D. R., Dewey, W. L., and Martin, B. R. (1990). Cannabis dependence and tolerance production. Adv.Alcohol Subst.Abuse. 9: 129-147.
214. Pertwee, R. Tolerance to and dependence on psychotropic cannabinoids. The biological bases of drug tolerance and dependence. Pratt, J. London: Academic Press, 1991.
215. De Vry, J., Jentzsch, K. R., Kuhl, E., and Eckel, G. (2004). Behavioral effects of cannabinoids show differential sensitivity to cannabinoid receptor blockade and tolerance development. Behav.Pharmacol. 15: 1-12.
216. D’Souza, D. C., Ranganathan, M., Braley, G., Gueorguieva, R. and others. (2008). Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology. 33: 2505-2516.
217. Rog, D. J., Nurmikko, T. J., and Young, C. A. (2007). Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin.Ther. 29: 2068-2079.
218. Serpell, M. G., Notcutt, W., and Collin, C. (2012). Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J.Neurol. 260: 285-295.
219. Hall, W. and Solowij, N. The adverse health and psychological consequences of cannabis dependence. Cannabis dependence. Roffman, R. A. and Stephens, R. S. Cambridge: Cambridge University Press, 2006.
220. Kalant, H. (2004). Adverse effects of cannabis on health: an update of the literature since 1996. Prog.Neuropsychopharmacol.Biol.Psychiatry. 28: 849-863.
221. Cooper, Z. D. and Haney, M. (2008). Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor. Addict.Biol. 13: 188-195.
222. Allsop, D. J., Norberg, M. M., Copeland, J., Fu, S. and others. (2011). The Cannabis Withdrawal Scale development: patterns and predictors of cannabis withdrawal and distress. Drug Alcohol Depend. 119: 123-129.
223. Renault, P. F., Schuster, C. R., Heinrich, R., and Freeman, D. X. (1971). Marihuana: standardized smoke administration and dose effect curves on heart rate in humans. Science. 174: 589-591.
224. Clark, S. C., Greene, C., Karr, G. W., MacCannell, K. L. and others. (1974). Cardiovascular effects of marihuana in man. Can.J.Physiol Pharmacol. 52: 706-719.
225. O’Leary, D. S., Block, R. I., Koeppel, J. A., Flaum, M. and others. (2002). Effects of smoking marijuana on brain perfusion and cognition. Neuropsychopharmacology. 26: 802-816.
226. Trouve, R. and Nahas, G. Cardiovascular effects of marihuana and cannabinoids. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
227. Jones, R. T. (2002). Cardiovascular system effects of marijuana. J.Clin.Pharmacol. 42: 58S-63S.
228. Hollister, L. E. (1986). Health aspects of cannabis. Pharmacol.Rev. 38: 1-20.
229. Miller, R. H., Dhingra, R. C., Kanakis, C., Jr., Leon, F. and others. (1977). The electrophysiological effects of delta9-tetrahydrocannabinol (cannabis) on cardiac conduction in man. Am.Heart J. 94: 740-747.
230. Lindsay, A. C., Foale, R. A., Warren, O., and Henry, J. A. (2005). Cannabis as a precipitant of cardiovascular emergencies. Int.J.Cardiol. 104: 230-232.
231. Beaconsfield, P. (1974). Some cardiovascular effects of cannabis. Am.Heart J. 87: 143-146.
232. Mittleman, M. A., Lewis, R. A., Maclure, M., Sherwood, J. B. and others. (2001). Triggering myocardial infarction by marijuana. Circulation. 103: 2805-2809.
233. Mathew, R. J., Wilson, W. H., and Davis, R. (2003). Postural syncope after marijuana: a transcranial Doppler study of the hemodynamics. Pharmacol.Biochem.Behav. 75: 309-318.
234. Gorelick, D. A. and Heishman, S. J. (2006). Methods for clinical research involving cannabis administration. Methods Mol.Med. 123: 235-253.
235. Lundqvist, T. (2005). Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions. Pharmacol.Biochem.Behav. 81: 319-330.
236. Singh, N. N., Pan, Y., Muengtaweeponsa, S., Geller, T. J. and others. (2012). Cannabis-related stroke: case series and review of literature. J.Stroke Cerebrovasc.Dis. 21: 555-560.
237. Renard, D., Taieb, G., Gras-Combe, G., and Labauge, P. (2012). Cannabis-related myocardial infarction and cardioembolic stroke. J.Stroke Cerebrovasc.Dis. 21: 82-83.
238. Sidney, S., Quesenberry Jr, C. P., Friedman, G. D., and Tekawa, I. S. (1997). Marijuana use and cancer incidence (California, United States). Cancer Causes Control. 8: 722-728.
239. Zhang, Z. F., Morgenstern, H., Spitz, M. R., Tashkin, D. P. and others. (1999). Marijuana use and increased risk of squamous cell carcinoma of the head and neck. Cancer Epidemiol.Biomarkers Prev. 8: 1071-1078.
240. Hashibe, M., Morgenstern, H., Cui, Y., Tashkin, D. P. and others. (2006). Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiol.Biomarkers Prev. 15: 1829-1834.
241. Aldington, S., Harwood, M., Cox, B., Weatherall, M. and others. (2008). Cannabis use and risk of lung cancer: a case-control study. Eur.Respir.J. 31: 280-286.
242. Fligiel, S. E., Roth, M. D., Kleerup, E. C., Barsky, S. H. and others. (1997). Tracheobronchial histopathology in habitual smokers of cocaine, marijuana, and/or tobacco. Chest. 112: 319-326.
243. Tetrault, J. M., Crothers, K., Moore, B. A., Mehra, R. and others. (2007). Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch.Intern.Med. 167: 221-228.
244. Bloom, J. W., Kaltenborn, W. T., Paoletti, P., Camilli, A. and others. (1987). Respiratory effects of non-tobacco cigarettes. Br.Med.J.(Clin.Res.Ed). 295: 1516-1518.
245. Tashkin, D. P., Coulson, A. H., Clark, V. A., Simmons, M. and others. (1987). Respiratory symptoms and lung function in habitual heavy smokers of marijuana alone, smokers of marijuana and tobacco, smokers of tobacco alone, and nonsmokers. Am.Rev.Respir.Dis. 135: 209-216.
246. Roth, M. D., Arora, A., Barsky, S. H., Kleerup, E. C. and others. (1998). Airway inflammation in young marijuana and tobacco smokers. Am.J.Respir.Crit Care Med. 157: 928-937.
247. Pletcher, M. J., Vittinghoff, E., Kalhan, R., Richman, J. and others. (2012). Association between marijuana exposure and pulmonary function over 20 years. JAMA. 307: 173-181.
248. Naftali, T., Lev, L. B., Yablecovitch, D., Half, E. and others. (2011). Treatment of Crohn’s disease with cannabis: an observational study. Isr.Med.Assoc.J. 13: 455-458.
249. Patsenker, E., Stoll, M., Millonig, G., Agaimy, A. and others. (2011). Cannabinoid receptor type I modulates alcohol-induced liver fibrosis. Mol.Med. 17: 1285-1294.
250. Trebicka, J., Racz, I., Siegmund, S. V., Cara, E. and others. (2011). Role of cannabinoid receptors in alcoholic hepatic injury: steatosis and fibrogenesis are increased in CB2 receptor-deficient mice and decreased in CB1 receptor knockouts. Liver Int. 31: 860-870.
251. Reichenbach, V., Ros, J., Fernandez-Varo, G., Casals, G. and others. (2012). Prevention of fibrosis progression in CCl4-treated rats: role of the hepatic endocannabinoid and apelin systems. J.Pharmacol.Exp.Ther. 340: 629-637.
252. Sylvestre, D. L., Clements, B. J., and Malibu, Y. (2006). Cannabis use improves retention and virological outcomes in patients treated for hepatitis C. Eur.J.Gastroenterol.Hepatol. 18: 1057-1063.
253. Grant, P. and Gandhi, P. (2004). A case of cannabis-induced pancreatitis. JOP. 5: 41-43.
254. Wargo, K. A., Geveden, B. N., and McConnell, V. J. (2007). Cannabinoid-induced pancreatitis: a case series. JOP. 8: 579-583.
255. Bournet, B. and Buscail, L. (2008). [Cannabis: a rare cause of acute pancreatitis]. Gastroenterol.Clin.Biol. 32: 922923.
256. Belze, O., Jr., Legras, A., Ehrmann, S., Garot, D. and others. (2011). Cannabis-induced acute pancreatitis. Am.J.Emerg.Med. 29: 131-134.
257. Cox, M. L., Haller, V. L., and Welch, S. P. (2007). Synergy between delta9-tetrahydrocannabinol and morphine in the arthritic rat. Eur.J.Pharmacol. 567: 125-130.
258. Smith, F. L., Fujimori, K., Lowe, J., and Welch, S. P. (1998). Characterization of delta9-tetrahydrocannabinol and anandamide antinociception in nonarthritic and arthritic rats. Pharmacol.Biochem.Behav. 60: 183-191.
259. Blake, D. R., Robson, P., Ho, M., Jubb, R. W. and others. (2006). Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology.(Oxford). 45: 50-52.
260. Schley, M., Legler, A., Skopp, G., Schmelz, M. and others. (2006). Delta-9-THC based monotherapy in fibromyalgia patients on experimentally induced pain, axon reflex flare, and pain relief. Curr.Med.Res.Opin. 22: 12691276.
261. Weber, J., Schley, M., Casutt, M., Gerber, H. and others. (2009). Tetrahydrocannabinol (Delta 9-THC) Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey. Anesthesiol.Res.Pract. 2009: 827290.-
262. Zajicek, J., Fox, P., Sanders, H., Wright, D. and others. (2003). Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 362: 1517-1526.
263. Nogueira-Filho, Gda R., Cadide, T., Rosa, B. T., Neiva, T. G. and others. (2008). Cannabis sativa smoke inhalation decreases bone filling around titanium implants: a histomorphometric study in rats. Implant.Dent. 17: 461470.
264. Tomida, I., Azuara-Blanco, A., House, H., Flint, M. and others. (2006). Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J.Glaucoma. 15: 349-353.
265. Tomida, I., Pertwee, R. G., and zuara-Blanco, A. (2004). Cannabinoids and glaucoma. Br.J.Ophthalmol. 88: 708713.
266. Tanasescu, R. and Constantinescu, C. S. (2010). Cannabinoids and the immune system: an overview. Immunobiology. 215: 588-597.
267. Nahas, G. G., Frick, H. C., Lattimer, J. K., Latour, C. and others. (2002). Pharmacokinetics of THC in brain and testis, male gametotoxicity and premature apoptosis of spermatozoa. Hum.Psychopharmacol. 17: 103-113.
268. Sadeu, J. C., Hughes, C. L., Agarwal, S., and Foster, W. G. (2010). Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications. Crit Rev.Toxicol. 40: 633-652.
269. Gorzalka, B. B., Hill, M. N., and Chang, S. C. (2010). Male-female differences in the effects of cannabinoids on sexual behavior and gonadal hormone function. Horm.Behav. 58: 91-99.
270. Brown, T. T. and Dobs, A. S. (2002). Endocrine effects of marijuana. J.Clin.Pharmacol. 42: 90S-96S.
271. Shamloul, R. and Bella, A. J. (2011). Impact of cannabis use on male sexual health. J.Sex Med. 8: 971-975.
272. Agurell, S., Halldin, M., Lindgren, J. E., Ohlsson, A. and others. (1986). Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol.Rev. 38: 21-43.
273. Abrams, D. I., Vizoso, H. P., Shade, S. B., Jay, C. and others. (2007). Vaporization as a Smokeless Cannabis Delivery System: A Pilot Study. Clin.Pharmacol.Ther. 82: 572-578.
274. McClure, E. A., Stitzer, M. L., and Vandrey, R. (2012). Characterizing smoking topography of cannabis in heavy users. Psychopharmacology (Berl). 220: 309-318.
275. Grotenhermen, F. (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clin.Pharmacokinet. 42: 327360.
276. Huestis, M. A. (2005). Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb.Exp.Pharmacol. 657-690.
277. Carter, G. T., Weydt, P., Kyashna-Tocha, M., and Abrams, D. I. (2004). Medicinal cannabis: rational guidelines for dosing. IDrugs. 7: 464-470.
278. Ohlsson, A., Lindgren, J. E., Wahlen, A., Agurell, S. and others. (1980). Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin.Pharmacol.Ther. 28: 409-416.
279. Cooper, Z. D. and Haney, M. (2009). Comparison of subjective, pharmacokinetic, and physiological effects of marijuana smoked as joints and blunts. Drug Alcohol Depend. 103: 107-113.
280. Schwope, D. M., Bosker, W. M., Ramaekers, J. G., Gorelick, D. A. and others. (2012). Psychomotor performance, subjective and physiological effects and whole blood Delta(9)-tetrahydrocannabinol concentrations in heavy, chronic cannabis smokers following acute smoked cannabis. J.Anal.Toxicol. 36: 405-412.
281. Gieringer, D. H. (2001). Cannabis “Vaporization”. Journal of Cannabis Therapeutics. 1: 153-170.
282. Gieringer, D., St Laurent, J., and Goodrich, S. (2004). Cannabis vaporizer combines efficient delivery of THC with effective suppression of pyrolytic compounds. Journal of Cannabis Therapeutics. 4: 7-27.
283. Hazekamp, A., Ruhaak, R., Zuurman, L., van, Gerven J. and others. (2006). Evaluation of a vaporizing device (Volcano) for the pulmonary administration of tetrahydrocannabinol. J.Pharm.Sci. 95: 1308-1317.
284. Pomahacova, B., Van der Kooy, F., and Verpoorte, R. (2009). Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa. Inhal.Toxicol. 21: 1108-1112.
285. Walsh, D., Nelson, K. A., and Mahmoud, F. A. (2003). Established and potential therapeutic applications of cannabinoids in oncology. Support.Care Cancer. 11: 137-143.
286. Cone, E. J., Johnson, R. E., Paul, B. D., Mell, L. D. and others. (1988). Marijuana-laced brownies: behavioral effects, physiologic effects, and urinalysis in humans following ingestion. J.Anal.Toxicol. 12: 169-175.
287. Iversen, L. L. The pharmacology of THC, the psychoactive ingredient in cannabis. The science of marijuana. New York, New York; Oxford University Press, 2000.
288. Schwilke, E. W., Schwope, D. M., Karschner, E. L., Lowe, R. H. and others. (2009). Delta9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC. Clin.Chem. 55: 2180-2189.
289. Office of Medicinal Cannabis, The Netherlands Ministry of Health Welfare and Sports. Medicinal Cannabis, Information for Health Care Professionals. 2008.
290. GW Pharmaceuticals. Sativex Product Monograph. 2010.
291. Wade, D. T., Makela, P., Robson, P., House, H. and others. (2004). Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebocontrolled study on 160 patients. Mult.Scler. 10: 434-441.
292. Nurmikko, T. J., Serpell, M. G., Hoggart, B., Toomey, P. J. and others. (2007). Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 133: 210-220.
293. Brenneisen, R., Egli, A., Elsohly, M. A., Henn, V. and others. (1996). The effect of orally and rectally administered delta 9-tetrahydrocannabinol on spasticity: a pilot study with 2 patients. Int.J.Clin.Pharmacol.Ther. 34: 446-452.
294. Mattes, R. D., Shaw, L. M., Edling-Owens, J., Engelman, K. and others. (1993). Bypassing the first-pass effect for the therapeutic use of cannabinoids. Pharmacol.Biochem.Behav. 44: 745-747.
295. Perlin, E., Smith, C. G., Nichols, A. I., Almirez, R. and others. (1985). Disposition and bioavailability of various formulations of tetrahydrocannabinol in the rhesus monkey. J.Pharm.Sci. 74: 171-174.
296. Elsohly, M. A., Little, T. L., Jr., Hikal, A., Harland, E. and others. (1991). Rectal bioavailability of delta-9tetrahydrocannabinol from various esters. Pharmacol.Biochem.Behav. 40: 497-502.
297. Elsohly, M. A., Stanford, D. F., Harland, E. C., Hikal, A. H. and others. (1991). Rectal bioavailability of delta-9tetrahydrocannabinol from the hemisuccinate ester in monkeys. J.Pharm.Sci. 80: 942-945.
298. Valiveti, S., Hammell, D. C., Earles, D. C., and Stinchcomb, A. L. (2004). Transdermal delivery of the synthetic cannabinoid WIN 55,212-2: in vitro/in vivo correlation. Pharm.Res. 21: 1137-1145.
299. Valiveti, S., Kiptoo, P. K., Hammell, D. C., and Stinchcomb, A. L. (2004). Transdermal permeation of WIN 55,2122 and CP 55,940 in human skin in vitro. Int.J.Pharm. 278: 173-180.
300. Stinchcomb, A. L., Valiveti, S., Hammell, D. C., and Ramsey, D. R. (2004). Human skin permeation of Delta8tetrahydrocannabinol, cannabidiol and cannabinol. J.Pharm.Pharmacol. 56: 291-297.
301. Harvey, D. J. Absorption, distribution and biotransformation of the cannabinoids. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
302. Widman, M., Agurell, S., Ehrnebo, M., and Jones, G. (1974). Binding of (+)- and (minus)-delta-1tetrahydrocannabinols and (minus)-7-hydroxy-delta-1-tetrahydrocannabinol to blood cells and plasma proteins in man. J.Pharm.Pharmacol. 26: 914-916.
303. Garrett, E. R. and Hunt, C. A. (1977). Pharmacokinetics of delta9-tetrahydrocannabinol in dogs. J.Pharm.Sci. 66: 395-407.
304. Wahlqvist, M., Nilsson, I. M., Sandberg, F., and Agurell, S. (1970). Binding of delta-1-tetrahydrocannabinol to human plasma proteins. Biochem.Pharmacol. 19: 2579-2584.
305. Widman, M., Nilsson, I. M., Agurell, S., Borg, H. and others. (1973). Plasma protein binding of 7-hydroxy- 1tetrahydrocannabinol: an active 1-tetrahydrocannabinol metabolite. J.Pharm.Pharmacol. 25: 453-457.
306. Truitt, E. B., Jr. (1971). Biological disposition of tetrahydrocannabinols. Pharmacol.Rev. 23: 273-278.
307. Nahas, G. G. (2001). The pharmacokinetics of THC in fat and brain: resulting functional responses to marihuana smoking. Hum.Psychopharmacol. 16: 247-255.
308. Schou, J., Prockop, L. D., Dahlstrom, G., and Rohde, C. (1977). Penetration of delta-9-tetrahydrocannabinol and 11OH-delta-9-tetrahydrocannabinol through the blood-brain barrier. Acta Pharmacol.Toxicol.(Copenh). 41: 33-38.
309. Mura, P., Kintz, P., Dumestre, V., Raul, S. and others. (2005). THC can be detected in brain while absent in blood. J.Anal.Toxicol. 29: 842-843.
310. Gunasekaran, N., Long, L. E., Dawson, B. L., Hansen, G. H. and others. (2009). Reintoxication: the release of fatstored delta(9)-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure. Br.J.Pharmacol. 158: 1330-1337.
311. Lemberger, L. (1973). Tetrahydrocannabinol metabolism in man. Drug Metab Dispos. 1: 461-468.
312. Wall, M. E., Sadler, B. M., Brine, D., Taylor, H. and others. (1983). Metabolism, disposition, and kinetics of delta-9tetrahydrocannabinol in men and women. Clin.Pharmacol.Ther. 34: 352-363.
313. Christensen, H. D., Freudenthal, R. I., Gidley, J. T., Rosenfeld, R. and others. (1971). Activity of delta8- and delta9tetrahydrocannabinol and related compounds in the mouse. Science. 172: 165-167.
314. Perez-Reyes, M., Timmons, M. C., Lipton, M. A., Davis, K. H. and others. (1972). Intravenous injection in man of 9 -tetrahydrocannabinol and 11-OH- 9 -tetrahydrocannabinol. Science. 177: 633-635.
315. Huestis, M. A., Mitchell, J. M., and Cone, E. J. (1996). Urinary excretion profiles of 11-nor-9-carboxy-delta 9tetrahydrocannabinol in humans after single smoked doses of marijuana. J.Anal.Toxicol. 20: 441-452.
316. Hawks, R. L. (1982). The constituents of cannabis and the disposition and metabolism of cannabinoids. NIDA Res.Monogr. 42: 125-137.
317. Martin, B. R. and Cone, E. J. Chemistry and pharmacology of cannabis. The Health Effects of Cannabis. Kalant, H., Corrigall, W., Hall, W., and Smart, R. Toronto, Canada: Centre of Addiction and Mental Health, 1999.
318. Sachse-Seeboth, C., Pfeil, J., Sehrt, D., Meineke, I. and others. (2009). Interindividual variation in the pharmacokinetics of Delta9-tetrahydrocannabinol as related to genetic polymorphisms in CYP2C9. Clin.Pharmacol.Ther. 85: 273-276.
319. Oates, J. A. The science of drug therapy. Goodman and Gilman’s the pharmacological basis of therapeutics. Brunton, L. L., Lazo, J. S., and Parker, K. L. New York: McGraw-Hill, 2006.
320. Graham, M. J. and Lake, B. G. (2008). Induction of drug metabolism: species differences and toxicological relevance. Toxicology. 254: 184-191.
321. Bornheim, L. M., Everhart, E. T., Li, J., and Correia, M. A. (1993). Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem.Pharmacol. 45: 1323-1331.
322. Kosel, B. W., Aweeka, F. T., Benowitz, N. L., Shade, S. B. and others. (2002). The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir. AIDS. 16: 543-550.
323. Jusko, W. J., Schentag, J. J., Clark, J. H., Gardner, M. and others. (1978). Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin.Pharmacol.Ther. 24: 405-410.
324. Zullino, D. F., Delessert, D., Eap, C. B., Preisig, M. and others. (2002). Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine. Int.Clin.Psychopharmacol. 17: 141-143.
325. Huestis, M. A., Henningfield, J. E., and Cone, E. J. (1992). Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J.Anal.Toxicol. 16: 276-282.
326. Agurell, S. and Leander, K. (1971). Stability, transfer and absorption of cannabinoid constituents of cannabis (hashish) during smoking. Acta Pharm.Suec. 8: 391-402.
327. Wall, M. E. and Perez-Reyes, M. (1981). The metabolism of delta 9-tetrahydrocannabinol and related cannabinoids in man. J.Clin.Pharmacol. 21: 178S-189S.
328. Huestis, M. A., Sampson, A. H., Holicky, B. J., Henningfield, J. E. and others. (1992). Characterization of the absorption phase of marijuana smoking. Clin.Pharmacol.Ther. 52: 31-41.
329. Johansson, E., Agurell, S., Hollister, L. E., and Halldin, M. M. (1988). Prolonged apparent half-life of delta 1tetrahydrocannabinol in plasma of chronic marijuana users. J.Pharm.Pharmacol. 40: 374-375.
330. Cone, E. J. and Huestis, M. A. (1993). Relating blood concentrations of tetrahydrocannabinol and metabolites to pharmacologic effects and time of marijuana usage. Ther.Drug Monit. 15: 527-532.
331. Toennes, S. W., Ramaekers, J. G., Theunissen, E. L., Moeller, M. R. and others. (2008). Comparison of cannabinoid pharmacokinetic properties in occasional and heavy users smoking a marijuana or placebo joint. J.Anal.Toxicol. 32: 470-477.
332. Valeant Canada. Cesamet Product Monograph. 2009.
333. Hollister, L. E., Gillespie, H. K., Ohlsson, A., Lindgren, J. E. and others. (1981). Do plasma concentrations of delta 9-tetrahydrocannabinol reflect the degree of intoxication? J.Clin.Pharmacol. 21: 171S-177S.
334. Strougo, A., Zuurman, L., Roy, C., Pinquier, J. L. and others. (2008). Modelling of the concentration–effect relationship of THC on central nervous system parameters and heart rate — insight into its mechanisms of action and a tool for clinical research and development of cannabinoids. J.Psychopharmacol. 22: 717-726.
335. Lynch, M. E. and Watson, C. P. (2006). The pharmacotherapy of chronic pain: a review. Pain Res.Manag. 11: 11-38.
336. Wu, D. F., Yang, L. Q., Goschke, A., Stumm, R. and others. (2008). Role of receptor internalization in the agonistinduced desensitization of cannabinoid type 1 receptors. J.Neurochem. 104: 1132-1143.
337. Maldonado, R. (2002). Study of cannabinoid dependence in animals. Pharmacol.Ther. 95: 153-164.
338. Pertwee, R. G. (2009). Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br.J.Pharmacol. 156: 397-411.
339. Hirvonen, J., Goodwin, R. S., Li, C. T., Terry, G. E. and others. (2012). Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Mol.Psychiatry. 17: 642-649.
340. Haney, M., Ward, A. S., Comer, S. D., Foltin, R. W. and others. (1999). Abstinence symptoms following smoked marijuana in humans. Psychopharmacology (Berl). 141: 395-404.
341. American Psychiatric Association. Substance-related disorders. Diagnostic and statistical manual of mental disorders text revision (DSM-IV-TR). American Psychiatric Association. Washington, D.C.: American Psychiatric Association, 2000.
342. Budney, A. J., Hughes, J. R., Moore, B. A., and Vandrey, R. (2004). Review of the validity and significance of cannabis withdrawal syndrome. Am.J.Psychiatry. 161: 1967-1977.
343. Hazekamp, A., Bastola, K., Rashidi, H., Bender, J. and others. (2007). Cannabis tea revisited: a systematic evaluation of the cannabinoid composition of cannabis tea. J.Ethnopharmacol. 113: 85-90.
344. Pertwee, R. G. (1974). Tolerance to the effect of delta1-tetrahydrocannabinol on corticosterone levels in mouse plasma produced by repeated administration of cannabis extract or delta1-tetrahydrocannabinol. Br.J.Pharmacol. 51: 391-397.
345. Lozano, I. (2001). The therapeutic uses of Cannabis sativa (L.) in Arabic medicine. Journal of Cannabis Therapeutics. 1: 63-70.
346. Russo, E. History of cannabis as a medicine. The Medicinal Uses of Cannabis and Cannabinoids. Guy, G. W., Whittle, B. A., and Robson, P. J. London: Pharmaceutical Press, 2004.
347. Russo, E. B. (2007). History of cannabis and its preparations in saga, science, and sobriquet. Chem.Biodivers. 4: 1614-1648.
348. Fraser, G. A. (2009). The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS.Neurosci.Ther. 15: 84-88.
349. Portenoy, R. K., Ganae-Motan, E. D., Allende, S., Yanagihara, R. and others. (2012). Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J.Pain. 13: 438-449.
350. Ware, M. A., Adams, H., and Guy, G. W. (2005). The medicinal use of cannabis in the UK: results of a nationwide survey. Int.J.Clin.Pract. 59: 291-295.
351. World Health Organization (WHO). Cannabis: a health perspective and research agenda. 1997
352. Cami, J., Guerra, D., Ugena, B., Segura, J. and others. (1991). Effect of subject expectancy on the THC intoxication and disposition from smoked hashish cigarettes. Pharmacol.Biochem.Behav. 40: 115-119.
353. Skrabek, R. Q., Galimova, L., Ethans, K., and Perry, D. (2008). Nabilone for the treatment of pain in fibromyalgia. J.Pain. 9: 164-173.
354. Ware, M. A., Fitzcharles, M. A., Joseph, L., and Shir, Y. (2010). The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth.Analg. 110: 604-610.
355. Kalliomaki, J., Philipp, A., Baxendale, J., Annas, P. and others. (2012). Lack of effect of central nervous systemactive doses of nabilone on capsaicin-induced pain and hyperalgesia. Clin.Exp.Pharmacol.Physiol. 39: 336-342.
356. World Health Organization (WHO). WHO Definition of Palliative Care. 2012.
357. Green, A. J. and De-Vries, K. (2010). Cannabis use in palliative care – an examination of the evidence and the implications for nurses. J.Clin.Nurs. 19: 2454-2462.
358. Gardiner, C. and Ingleton, C. (2010). Commentary on Green AJ & De-Vries K (2010) Cannabis use in palliative care–an examination of the evidence and the implications for nurses. Journal of Clinical Nursing 19, 24542462. J.Clin.Nurs. 19: 3253-3255.
359. Glare, P., Miller, J., Nikolova, T., and Tickoo, R. (2011). Treating nausea and vomiting in palliative care: a review. Clin.Interv.Aging. 6: 243-259.
360. Fine, P. G. (2012). Treatment guidelines for the pharmacological management of pain in older persons. Pain Med. 13 Suppl 2: S57-S66.
361. Svendsen, K. B., Jensen, T. S., and Bach, F. W. (2004). Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ. 329: 253-260.
362. Brisbois, T. D., de Kock, I. H., Watanabe, S. M., Mirhosseini, M. and others. (2011). Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann.Oncol. 22: 2086-2093.
363. Strasser, F., Luftner, D., Possinger, K., Ernst, G. and others. (2006). Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J.Clin.Oncol. 24: 3394-3400.
364. Toth, C., Mawani, S., Brady, S., Chan, C. and others. (2012). An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain. 153: 2073-2082.
365. Selvarajah, D., Gandhi, R., Emery, C. J., and Tesfaye, S. (2010). Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes Care. 33: 128-130.
366. Novotna, A., Mares, J., Ratcliffe, S., Novakova, I. and others. (2011). A randomized, double-blind, placebocontrolled, parallel-group, enriched-design study of nabiximols* (Sativex((R)) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur.J.Neurol. 18: 1122-1131.
367. Navari, R. M. (2009). Pharmacological management of chemotherapy-induced nausea and vomiting: focus on recent developments. Drugs. 69: 515-533.
368. Hornby, P. J. (2001). Central neurocircuitry associated with emesis. Am.J.Med. 111 Suppl 8A: 106S-112S.
369. Van Sickle, M. D., Duncan, M., Kingsley, P. J., Mouihate, A. and others. (2005). Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science. 310: 329-332.
370. Darmani, N. A. (2001). The cannabinoid CB1 receptor antagonist SR 141716A reverses the antiemetic and motor depressant actions of WIN 55, 212-2. Eur.J.Pharmacol. 430: 49-58.
371. Barann, M., Molderings, G., Bruss, M., Bonisch, H. and others. (2002). Direct inhibition by cannabinoids of human 5-HT3A receptors: probable involvement of an allosteric modulatory site. Br.J.Pharmacol. 137: 589-596.
372. Rock, E. M., Bolognini, D., Limebeer, C. L., Cascio, M. G. and others. (2012). Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. Br.J.Pharmacol. 165: 2620-2634.
373. Rock, E. M., Goodwin, J. M., Limebeer, C. L., Breuer, A. and others. (2011). Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews. Psychopharmacology (Berl). 215: 505-512.
374. Machado Rocha, F. C., Stefano, S. C., De Cassia, Haiek R., Rosa Oliveira, L. M. and others. (2008). Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur.J.Cancer Care (Engl.). 17: 431-443.
375. Meiri, E., Jhangiani, H., Vredenburgh, J. J., Barbato, L. M. and others. (2007). Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr.Med.Res.Opin. 23: 533-543.
376. Kwiatkowska, M., Parker, L. A., Burton, P., and Mechoulam, R. (2004). A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacology (Berl). 174: 254-259.
377. Wang, Y., Ray, A. P., McClanahan, B. A., and Darmani, N. A. (2009). The antiemetic interaction of Delta9tetrahydrocannabinol when combined with tropisetron or dexamethasone in the least shrew. Pharmacol.Biochem.Behav. 91: 367-373.
378. Institute of Medicine. The medical value of marijuana and related substances. Marijuana and medicine: Assessing the science base. Joy, J. E., Watson, S. J., and Benson, J. A. Washington, DC: National Academy Press, 1999.
379. Health Department of New South Wales, Australia. Working Party on the Use of Cannabis for Medical Purposes. (2000). 2.
380. Herrstedt, J. and Dombernowsky, P. (2007). Anti-emetic therapy in cancer chemotherapy: current status. Basic Clin.Pharmacol.Toxicol. 101: 143-150.
381. Canadian Pharmacists Association. Compendium of Pharmaceuticals and Specialties. Ottawa: Canadian Pharmacists Association, 2009.
382. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. 2010.
383. Clary, P. L. and Lawson, P. (2009). Pharmacologic pearls for end-of-life care. Am.Fam.Physician. 79: 1059-1065.
384. Minister of Justice, Government of Canada. Marihuana Medical Access Regulations. 2011.
385. Smit, E. and Crespo, C. J. (2001). Dietary intake and nutritional status of US adult marijuana users: results from the Third National Health and Nutrition Examination Survey. Public Health Nutr. 4: 781-786.
386. Di Marzo, V. and Matias, I. (2005). Endocannabinoid control of food intake and energy balance. Nat.Neurosci. 8: 585-589.
387. Matias, I., Bisogno, T., and Di, Marzo, V. (2006). Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake. Int.J.Obes.(Lond). 30 Suppl 1: S7-S12.
388. Tibirica, E. (2010). The multiple functions of the endocannabinoid system: a focus on the regulation of food intake. Diabetol.Metab Syndr. 2: 5-10.
389. Farrimond, J. A., Mercier, M. S., Whalley, B. J., and Williams, C. M. (2011). Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation. Phytother.Res. 25: 170-188.
390. Abrams, D. I., Hilton, J. F., Leiser, R. J., Shade, S. B. and others. (2003). Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Ann.Intern.Med. 139: 258266.
391. Ravinet-Trillou, C., Delgorge, C., Menet, C., Arnone, M. and others. (2004). CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int.J.Obes.Relat Metab Disord. 28: 640-648.
392. Timpone, J. G., Wright, D. J., Li, N., Egorin, M. J. and others. (1997). The safety and pharmacokinetics of singleagent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting
syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AIDS Res.Hum.Retroviruses. 13: 305-315.
393. Beal, J. E., Olson, R., Laubenstein, L., Morales, J. O. and others. (1995). Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J.Pain Symptom.Manage. 10: 89-97.
394. Beal, J. E., Olson, R., Lefkowitz, L., Laubenstein, L. and others. (1997). Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. J.Pain Symptom.Manage. 14: 7-14.
395. Tchekmedyian, N. S., Zahyna, D., Halpert, C., and Heber, D. (1992). Clinical aspects of nutrition in advanced cancer. Oncology. 49 Suppl 2: 3-7.
396. Walsh, D., Donnelly, S., and Rybicki, L. (2000). The symptoms of advanced cancer: relationship to age, gender, and performance status in 1,000 patients. Support.Care Cancer. 8: 175-179.
397. Ekert, H., Waters, K. D., Jurk, I. H., Mobilia, J. and others. (1979). Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol. Med.J.Aust. 2: 657-659.
398. Sallan, S. E., Cronin, C., Zelen, M., and Zinberg, N. E. (1980). Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N.Engl.J.Med. 302: 135-138.
399. Plasse, T. F., Gorter, R. W., Krasnow, S. H., Lane, M. and others. (1991). Recent clinical experience with dronabinol. Pharmacol.Biochem.Behav. 40: 695-700.
400. Nelson, K., Walsh, D., Deeter, P., and Sheehan, F. (1994). A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J.Palliat.Care. 10: 14-18.
401. Regelson, W., Butler, J. R., and Schulz, J. Delta-9-tetrahydrocannabinol as an effective antidepressant and appetitestimulating agent in advanced cancer patients. The Pharmacology of marihuana: A monograph of the National Institute on Drug Abuse. Braude, M. and Szara, S. New York: Raven Press, 1976.
402. Jatoi, A., Windschitl, H. E., Loprinzi, C. L., Sloan, J. A. and others. (2002). Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J.Clin.Oncol. 20: 567-573.
403. Mantovani, G., Maccio, A., Madeddu, C., Serpe, R. and others. (2010). Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist. 15: 200-211.
404. Monteleone, P., Matias, I., Martiadis, V., De, Petrocellis L. and others. (2005). Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa. Neuropsychopharmacology. 30: 1216-1221.
405. Siegfried, Z., Kanyas, K., Latzer, Y., Karni, O. and others. (2004). Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: differences between restricting and binging/purging subtypes. Am.J.Med.Genet.B Neuropsychiatr.Genet. 125B: 126-130.
406. Muller, T. D., Reichwald, K., Bronner, G., Kirschner, J. and others. (2008). Lack of association of genetic variants in genes of the endocannabinoid system with anorexia nervosa. Child Adolesc.Psychiatry Ment.Health. 2: 3339.
407. Lewis, D. Y. and Brett, R. R. (2010). Activity-based anorexia in C57/BL6 mice: effects of the phytocannabinoid, Delta9-tetrahydrocannabinol (THC) and the anandamide analogue, OMDM-2. Eur.Neuropsychopharmacol. 20: 622-631.
408. Verty, A. N., Evetts, M. J., Crouch, G. J., McGregor, I. S. and others. (2011). The cannabinoid receptor agonist THC attenuates weight loss in a rodent model of activity-based anorexia. Neuropsychopharmacology. 36: 13491358.
409. Gross, H., Ebert, M. H., Faden, V. B., Goldberg, S. C. and others. (1983). A double-blind trial of delta 9tetrahydrocannabinol in primary anorexia nervosa. J.Clin.Psychopharmacol. 3: 165-171.
410. Volicer, L., Stelly, M., Morris, J., McLaughlin, J. and others. (1997). Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int.J.Geriatr.Psychiatry. 12: 913-919.
411. American Medical Association, Council of Scientific Affairs. Medical Marijuana. Internet. American Medical Association, Council of Scientific Affairs. 1997.
412. Aggarwal, S. K., Carter, G. T., Sullivan, M. D., ZumBrunnen, C. and others. (2009). Characteristics of patients with chronic pain accessing treatment with medical cannabis in Washington State. J.Opioid.Manag. 5: 257-286.
413. Heutink, M., Post, M. W., Wollaars, M. M., and van Asbeck, F. W. (2011). Chronic spinal cord injury pain: pharmacological and non-pharmacological treatments and treatment effectiveness. Disabil.Rehabil. 33: 433-440.
414. Baker, D., Pryce, G., Croxford, J. L., Brown, P. and others. (2000). Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature. 404: 84-87.
415. Centonze, D., Rossi, S., Finazzi-Agro, A., Bernardi, G. and others. (2007). The (endo)cannabinoid system in multiple sclerosis and amyotrophic lateral sclerosis. Int.Rev.Neurobiol. 82: 171-186.
416. Di Filippo, M., Pini, L. A., Pelliccioli, G. P., Calabresi, P. and others. (2008). Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis. J.Neurol.Neurosurg.Psychiatry. 79: 1224-1229.
417. Jean-Gilles, L., Feng, S., Tench, C. R., Chapman, V. and others. (2009). Plasma endocannabinoid levels in multiple sclerosis. J.Neurol.Sci. 287: 212-215.
418. Pertwee, R. G. (2007). Cannabinoids and multiple sclerosis. Mol.Neurobiol. 36: 45-59.
419. Lyman, W. D., Sonett, J. R., Brosnan, C. F., Elkin, R. and others. (1989). Delta 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis. J.Neuroimmunol. 23: 73-81.
420. Maresz, K., Pryce, G., Ponomarev, E. D., Marsicano, G. and others. (2007). Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat.Med. 13: 492-497.
421. Pryce, G. and Baker, D. (2007). Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors. Br.J.Pharmacol. 150: 519-525.
422. Croxford, J. L., Pryce, G., Jackson, S. J., Ledent, C. and others. (2008). Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. J.Neuroimmunol. 193: 120-129.
423. Baker, D., Jackson, S. J., and Pryce, G. (2007). Cannabinoid control of neuroinflammation related to multiple sclerosis. Br.J.Pharmacol. 152: 649-654.
424. Sanchez, A. J. and Garcia-Merino, A. (2011). Neuroprotective agents: Cannabinoids. Clin.Immunol. 142: 57-67.
425. Consroe, P. and Sandyk, R. Therapeutic potential of cannabinoids in neurological disorders. Marijuana/Cannabinoids as therapeutic agents. Mechoulam, R. Boca Raton, FL: CRC Press, 1986.
426. Chong, M. S., Wolff, K., Wise, K., Tanton, C. and others. (2006). Cannabis use in patients with multiple sclerosis. Mult.Scler. 12: 646-651.
427. Zajicek, J. P., Sanders, H. P., Wright, D. E., Vickery, P. J. and others. (2005). Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J.Neurol.Neurosurg.Psychiatry. 76: 1664-1669.
428. Vaney, C., Heinzel-Gutenbrunner, M., Jobin, P., Tschopp, F. and others. (2004). Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult.Scler. 10: 417-424.
429. Wade, D. T., Makela, P. M., House, H., Bateman, C. and others. (2006). Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult.Scler. 12: 639-645.
430. Collin, C., Davies, P., Mutiboko, I. K., and Ratcliffe, S. (2007). Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur.J.Neurol. 14: 290-296.
431. Hobart, J. C., Riazi, A., Thompson, A. J., Styles, I. M. and others. (2006). Getting the measure of spasticity in multiple sclerosis: the Multiple Sclerosis Spasticity Scale (MSSS-88). Brain. 129: 224-234.
432. Zajicek, J. P., Hobart, J. C., Slade, A., Barnes, D. and others. (2012). MUltiple Sclerosis and Extract of Cannabis: results of the MUSEC trial. J.Neurol.Neurosurg.Psychiatry. 83: 1125-1132.
433. Killestein, J., Hoogervorst, E. L., Reif, M., Kalkers, N. F. and others. (2002). Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology. 58: 1404-1407.
434. Aragona, M., Onesti, E., Tomassini, V., Conte, A. and others. (2009). Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study. Clin.Neuropharmacol. 32: 41-47.
435. Freeman, R. M., Adekanmi, O., Waterfield, M. R., Waterfield, A. E. and others. (2006). The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS). Int.Urogynecol.J.Pelvic.Floor.Dysfunct. 17: 636-641.
436. Sliwa, J. A., Bell, H. K., Mason, K. D., Gore, R. M. and others. (1996). Upper urinary tract abnormalities in multiple sclerosis patients with urinary symptoms. Arch.Phys.Med.Rehabil. 77: 247-251.
437. Consroe, P., Musty, R., Rein, J., Tillery, W. and others. (1997). The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur.Neurol. 38: 44-48.
438. Brady, C. M., DasGupta, R., Dalton, C., Wiseman, O. J. and others. (2004). An open-label pilot study of cannabisbased extracts for bladder dysfunction in advanced multiple sclerosis. Mult.Scler. 10: 425-433.
439. Rossi, S., Bernardi, G., and Centonze, D. (2010). The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis. Exp.Neurol. 224: 92-102.
440. Scotter, E. L., Abood, M. E., and Glass, M. (2010). The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br.J.Pharmacol. 160: 480-498.
441. Amtmann, D., Weydt, P., Johnson, K. L., Jensen, M. P. and others. (2004). Survey of cannabis use in patients with amyotrophic lateral sclerosis. Am.J.Hosp.Palliat.Care. 21: 95-104.
442. Weber, M., Goldman, B., and Truniger, S. (2010). Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: a randomised, double-blind crossover trial. J.Neurol.Neurosurg.Psychiatry. 81: 1135-1140.
443. Gelinas, D. F, Miller, R. G, and Abood, M. (2002). Pilot study of safety and tolerability of delta 9-THC (Marinol) treatment for ALS. Amyotroph Lateral Scler Other Motor Neuron Disord. 3: 23-24.
444. Garcia-Ovejero, D., Arevalo-Martin, A., Petrosino, S., Docagne, F. and others. (2009). The endocannabinoid system is modulated in response to spinal cord injury in rats. Neurobiol.Dis. 33: 57-71.
445. Hama, A. and Sagen, J. (2007). Antinociceptive effect of cannabinoid agonist WIN 55,212-2 in rats with a spinal cord injury. Exp.Neurol. 204: 454-457.
446. Hama, A. and Sagen, J. (2009). Sustained antinociceptive effect of cannabinoid receptor agonist WIN 55,212-2 over time in rat model of neuropathic spinal cord injury pain. J.Rehabil.Res.Dev. 46: 135-143.
447. Malec, J., Harvey, R. F., and Cayner, J. J. (1982). Cannabis effect on spasticity in spinal cord injury. Arch.Phys.Med.Rehabil. 63: 116-118.
448. Maurer, M., Henn, V., Dittrich, A., and Hofmann, A. (1990). Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial. Eur.Arch.Psychiatry Clin.Neurosci. 240: 1-4.
449. Wade, D. T., Robson, P., House, H., Makela, P. and others. (2003). A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin.Rehabil. 17: 21-29.
450. Hagenbach, U., Luz, S., Ghafoor, N., Berger, J. M. and others. (2007). The treatment of spasticity with Delta9tetrahydrocannabinol in persons with spinal cord injury. Spinal Cord. 45: 551-562.
451. Pooyania, S., Ethans, K., Szturm, T., Casey, A. and others. (2010). A randomized, double-blinded, crossover pilot study assessing the effect of nabilone on spasticity in persons with spinal cord injury. Arch.Phys.Med.Rehabil. 91: 703-707.
452. Falenski, K. W., Blair, R. E., Sim-Selley, L. J., Martin, B. R. and others. (2007). Status epilepticus causes a longlasting redistribution of hippocampal cannabinoid type 1 receptor expression and function in the rat pilocarpine model of acquired epilepsy. Neuroscience. 146: 1232-1244.
453. Ludanyi, A., Eross, L., Czirjak, S., Vajda, J. and others. (2008). Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J.Neurosci. 28: 2976-2990.
454. Falenski, K. W., Carter, D. S., Harrison, A. J., Martin, B. R. and others. (2009). Temporal characterization of changes in hippocampal cannabinoid CB(1) receptor expression following pilocarpine-induced status epilepticus. Brain Res. 1262: 64-72.
455. Romigi, A., Bari, M., Placidi, F., Marciani, M. G. and others. (2010). Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy. Epilepsia. 51: 768-772.
456. Wallace, M. J., Martin, B. R., and DeLorenzo, R. J. (2002). Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur.J.Pharmacol. 452: 295-301.
457. Mechoulam, R. and Lichtman, A. H. (2003). Neuroscience. Stout guards of the central nervous system. Science. 302: 65-67.
458. Wallace, M. J., Blair, R. E., Falenski, K. W., Martin, B. R. and others. (2003). The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J.Pharmacol.Exp.Ther. 307: 129-137.
459. Shafaroodi, H., Samini, M., Moezi, L., Homayoun, H. and others. (2004). The interaction of cannabinoids and opioids on pentylenetetrazole-induced seizure threshold in mice. Neuropharmacology. 47: 390-400.
460. Clement, A. B., Hawkins, E. G., Lichtman, A. H., and Cravatt, B. F. (2003). Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolase. J.Neurosci. 23: 39163923.
461. Alger, B. E. (2002). Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids. Prog.Neurobiol. 68: 247-286.
462. Smith, P. F. (2005). Cannabinoids as potential anti-epileptic drugs. Curr.Opin.Investig.Drugs. 6: 680-685.
463. Hoffman, A. F. and Lupica, C. R. (2000). Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus. J.Neurosci. 20: 2470-2479.
464. Nakatsuka, T., Chen, H. X., Roper, S. N., and Gu, J. G. (2003). Cannabinoid receptor-1 activation suppresses inhibitory synaptic activity in human dentate gyrus. Neuropharmacology. 45: 116-121.
465. Gordon, E. and Devinsky, O. (2001). Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy. Epilepsia. 42: 1266-1272.
466. Lutz, B. (2004). On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. Biochem.Pharmacol. 68: 1691-1698.
467. Gloss, D. and Vickrey, B. (2012). Cannabinoids for epilepsy. Cochrane.Database.Syst.Rev. 6: CD009270-
468. Hama, A. T. and Sagen, J. (2010). Cannabinoid receptor-mediated antinociception with acetaminophen drug combinations in rats with neuropathic spinal cord injury pain. Neuropharmacology. 58: 758-766.
469. Manzanares, J., Julian, M., and Carrascosa, A. (2006). Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr.Neuropharmacol. 4: 239-257.
470. Christie, M. J. and Mallet, C. (2009). Endocannabinoids can open the pain gate. Sci.Signal. 2: pe57.-
471. Ostenfeld, T., Price, J., Albanese, M., Bullman, J. and others. (2011). A Randomized, Controlled Study to Investigate the Analgesic Efficacy of Single Doses of the Cannabinoid Receptor-2 Agonist GW842166, Ibuprofen or Placebo in Patients With Acute Pain Following Third Molar Tooth Extraction. Clin.J.Pain. 27: 668-676.
472. Karst, M., Wippermann, S., and Ahrens, J. (2010). Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs. 70: 2409-2438.
473. Mirchandani, A., Saleeb, M., and Sinatra, R. Acute and Chronic Mechanisms of Pain. Essentials of Pain Management. Vadivelu, N., Urman, R. D., and Hines, R. L. New York: Springer, 2011.
474. Seifert, F. and Maihofner, C. (2011). Functional and structural imaging of pain-induced neuroplasticity. Curr.Opin.Anaesthesiol. 24: 515-523.
475. Zubieta, J. K. and Stohler, C. S. (2009). Neurobiological mechanisms of placebo responses. Ann.N.Y.Acad.Sci. 1156: 198-210.
476. Finniss, D. G., Kaptchuk, T. J., Miller, F., and Benedetti, F. (2010). Biological, clinical, and ethical advances of placebo effects. Lancet. 375: 686-695.
477. Martin, B. R., Compton, D. R., Semus, S. F., Lin, S. and others. (1993). Pharmacological evaluation of iodo and nitro analogs of delta 8-THC and delta 9-THC. Pharmacol.Biochem.Behav. 46: 295-301.
478. Meng, I. D., Manning, B. H., Martin, W. J., and Fields, H. L. (1998). An analgesia circuit activated by cannabinoids. Nature. 395: 381-383.
479. Finn, D. P., Jhaveri, M. D., Beckett, S. R., Roe, C. H. and others. (2003). Effects of direct periaqueductal grey administration of a cannabinoid receptor agonist on nociceptive and aversive responses in rats. Neuropharmacology. 45: 594-604.
480. Azad, S. C., Monory, K., Marsicano, G., Cravatt, B. F. and others. (2004). Circuitry for associative plasticity in the amygdala involves endocannabinoid signaling. J.Neurosci. 24: 9953-9961.
481. Hill, S. Y., Schwin, R., Goodwin, D. W., and Powell, B. J. (1974). Marihuana and pain. J.Pharmacol.Exp.Ther. 188: 415-418.
482. Milstein, S. L., MacCannell, K., Karr, G., and Clark, S. (1975). Marijuana-produced changes in pain tolerance. Experienced and non-experienced subjects. Int.Pharmacopsychiatry. 10: 177-182.
483. Naef, M., Curatolo, M., Petersen-Felix, S., Arendt-Nielsen, L. and others. (2003). The analgesic effect of oral delta9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions. Pain. 105: 79-88.
484. Kraft, B., Frickey, N. A., Kaufmann, R. M., Reif, M. and others. (2008). Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers. Anesthesiology. 109: 101110.
485. Redmond, W. J., Goffaux, P., Potvin, S., and Marchand, S. (2008). Analgesic and antihyperalgesic effects of nabilone on experimental heat pain. Curr.Med.Res.Opin. 24: 1017-1024.
486. Holdcroft, A., Maze, M., Dore, C., Tebbs, S. and others. (2006). A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management. Anesthesiology. 104: 1040-1046.
487. Wu, C. L. and Raja, S. N. (2011). Treatment of acute postoperative pain. Lancet. 377: 2215-2225.
488. Jain, A. K., Ryan, J. R., McMahon, F. G., and Smith, G. (1981). Evaluation of intramuscular levonantradol and placebo in acute postoperative pain. J.Clin.Pharmacol. 21: 320S-326S.
489. Buggy, D. J., Toogood, L., Maric, S., Sharpe, P. and others. (2003). Lack of analgesic efficacy of oral delta-9tetrahydrocannabinol in postoperative pain. Pain. 106: 169-172.
490. Beaulieu, P. (2006). Effects of nabilone, a synthetic cannabinoid, on postoperative pain. Can.J.Anaesth. 53: 769-775.
491. Beaulieu, P. (2007). Cannabinoids for postoperative pain. Anesthesiology. 106: 397-398.
492. Voscopoulos, C. and Lema, M. (2010). When does acute pain become chronic? Br.J.Anaesth. 105 Suppl 1: i69-i85.
493. Fine, P. G., Burton, A. W., and Passik, S. D. (2012). Transformation of acute cancer pain to chronic cancer pain syndromes. J.Support.Oncol. 10: 89-95.
494. Berlach, D. M., Shir, Y., and Ware, M. A. (2006). Experience with the synthetic cannabinoid nabilone in chronic noncancer pain. Pain Med. 7: 25-29.
495. Walker, J. M. and Huang, S. M. (2002). Cannabinoid analgesia. Pharmacol.Ther. 95: 127-135.
496. Rahn, E. J. and Hohmann, A. G. (2009). Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics. 6: 713-737.
497. Costa, B., Trovato, A. E., Comelli, F., Giagnoni, G. and others. (2007). The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur.J.Pharmacol. 556: 75-83.
498. Toth, C. C., Jedrzejewski, N. M., Ellis, C. L., and Frey, W. H. (2010). Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. Mol.Pain. 6: 16-
499. Ashton, J. C. and Milligan, E. D. (2008). Cannabinoids for the treatment of neuropathic pain: clinical evidence. Curr.Opin.Investig.Drugs. 9: 65-75.
500. Grotenhermen, F. (2007). The toxicology of cannabis and cannabis prohibition. Chem.Biodivers. 4: 1744-1769.
501. Wilsey, B., Marcotte, T., Deutsch, R., Gouaux, B. and others. (2012). Low-Dose Vaporized Cannabis Significantly Improves Neuropathic Pain. J.Pain. 14: 136-148.
502. Narang, S., Gibson, D., Wasan, A. D., Ross, E. L. and others. (2008). Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. J.Pain. 9: 254-264.
503. Berman, J. S., Symonds, C., and Birch, R. (2004). Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 112: 299-306.
504. Rog, D. J., Nurmikko, T. J., Friede, T., and Young, C. A. (2005). Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 65: 812-819.
505. Moulin, D. E., Clark, A. J., Gilron, I., Ware, M. A. and others. (2007). Pharmacological management of chronic neuropathic pain – consensus statement and guidelines from the Canadian Pain Society. Pain Res.Manag. 12: 13-21.
506. Fitzcharles, M. A., Ste-Marie, P. A., Goldenberg, D. L., Pereira, J. X., Abbey, S., Choinier, M., Ko, G., Moulin, D., Panopalis, D., Proulx, J., and Shir, Y. 2012 Canadian Guidelines for the Diagnosis and Management of Fibromyalgia Syndrome. 2012.
507. Noyes, R., Jr., Brunk, S. F., Baram, D. A., and Canter, A. (1975). Analgesic effect of delta-9-tetrahydrocannabinol. J.Clin.Pharmacol. 15: 139-143.
508. Noyes, R., Jr., Brunk, S. F., Avery, D. A., and Canter, A. C. (1975). The analgesic properties of delta-9tetrahydrocannabinol and codeine. Clin.Pharmacol.Ther. 18: 84-89.
509. Johnson, J. R., Lossignol, D., Burnell-Nugent, M., and Fallon, M. T. (2012). An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics. J.Pain Symptom.Manage.
510. Bushlin, I., Rozenfeld, R., and Devi, L. A. (2010). Cannabinoid-opioid interactions during neuropathic pain and analgesia. Curr.Opin.Pharmacol. 10: 80-86.
511. Desroches, J. and Beaulieu, P. (2010). Opioids and cannabinoids interactions: involvement in pain management. Curr.Drug Targets. 11: 462-473.
512. Parolaro, D., Rubino, T., Vigano, D., Massi, P. and others. (2010). Cellular mechanisms underlying the interaction between cannabinoid and opioid system. Curr.Drug Targets. 11: 393-405.
513. Rios, C., Gomes, I., and Devi, L. A. (2006). mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis. Br.J.Pharmacol. 148: 387-395.
514. Rozenfeld, R., Bushlin, I., Gomes, I., Tzavaras, N. and others. (2012). Receptor heteromerization expands the repertoire of cannabinoid signaling in rodent neurons. PLoS.One. 7: e29239-
515. Welch, S. P. and Stevens, D. L. (1992). Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. J.Pharmacol.Exp.Ther. 262: 10-18.
516. Pugh, G., Jr., Smith, P. B., Dombrowski, D. S., and Welch, S. P. (1996). The role of endogenous opioids in enhancing the antinociception produced by the combination of delta 9-tetrahydrocannabinol and morphine in the spinal cord. J.Pharmacol.Exp.Ther. 279: 608-616.
517. Smith, F. L., Cichewicz, D., Martin, Z. L., and Welch, S. P. (1998). The enhancement of morphine antinociception in mice by delta9-tetrahydrocannabinol. Pharmacol.Biochem.Behav. 60: 559-566.
518. Cichewicz, D. L. and McCarthy, E. A. (2003). Antinociceptive synergy between delta(9)-tetrahydrocannabinol and opioids after oral administration. J.Pharmacol.Exp.Ther. 304: 1010-1015.
519. Cichewicz, D. L. (2004). Synergistic interactions between cannabinoid and opioid analgesics. Life Sci. 74: 13171324.
520. Smith, P. A., Selley, D. E., Sim-Selley, L. J., and Welch, S. P. (2007). Low dose combination of morphine and delta9-tetrahydrocannabinol circumvents antinociceptive tolerance and apparent desensitization of receptors. Eur.J.Pharmacol. 571: 129-137.
521. Roberts, J. D., Gennings, C., and Shih, M. (2006). Synergistic affective analgesic interaction between delta-9tetrahydrocannabinol and morphine. Eur.J.Pharmacol. 530: 54-58.
522. Greco, R., Gasperi, V., Maccarrone, M., and Tassorelli, C. (2010). The endocannabinoid system and migraine. Exp.Neurol. 224: 85-91.
523. Napchan, U., Buse, D. C., and Loder, E. W. (2011). The use of marijuana or synthetic cannabinoids for the treatment of headache. Headache. 51: 502-505.
524. McGeeney, B. E. (2012). Hallucinogens and cannabinoids for headache. Headache. 52 Suppl 2: 94-97.
525. Russo, E. B. (2004). Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro.Endocrinol.Lett. 25: 31-39.
526. Sarchielli, P., Pini, L. A., Coppola, F., Rossi, C. and others. (2007). Endocannabinoids in chronic migraine: CSF findings suggest a system failure. Neuropsychopharmacology. 32: 1384-1390.
527. Villalon, C. M. and Olesen, J. (2009). The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs. Pharmacol.Ther. 124: 309-323.
528. Cupini, L. M., Costa, C., Sarchielli, P., Bari, M. and others. (2008). Degradation of endocannabinoids in chronic migraine and medication overuse headache. Neurobiol.Dis. 30: 186-189.
529. Evans, R. W. and Ramadan, N. M. (2004). Are cannabis-based chemicals helpful in headache? Headache. 44: 726727.
530. Robbins, M. S., Tarshish, S., Solomon, S., and Grosberg, B. M. (2009). Cluster attacks responsive to recreational cannabis and dronabinol. Headache. 49: 914-916.
531. Leroux, E., Taifas, I., Valade, D., Donnet, A. and others. (2012). Use of cannabis among 139 cluster headache sufferers. Cephalalgia. 33: 208-213.
532. Ducros, A., Boukobza, M., Porcher, R., Sarov, M. and others. (2007). The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain. 130: 3091-3101.
533. Levin, K. H., Copersino, M. L., Heishman, S. J., Liu, F. and others. (2010). Cannabis withdrawal symptoms in nontreatment-seeking adult cannabis smokers. Drug Alcohol Depend. 111: 120-127.
534. Dunkley, L and Tattersall, R. (2012). Osteoarthritis and the inflammatory arthritides. Surgery. 30: 67-71.
535. Sagar, D. R., Staniaszek, L. E., Okine, B. N., Woodhams, S. and others. (2010). Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain. Arthritis Rheum. 62: 3666-3676.
536. Schuelert, N. and McDougall, J. J. (2008). Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum. 58: 145-153.
537. Schuelert, N., Johnson, M. P., Oskins, J. L., Jassal, K. and others. (2011). Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis. Pain. 152: 975-981.
538. Richards, B. L., Whittle, S. L., and Buchbinder, R. (2012). Neuromodulators for pain management in rheumatoid arthritis. Cochrane.Database.Syst.Rev. 1: CD008921-
539. McInnes, I. B. and Schett, G. (2011). The pathogenesis of rheumatoid arthritis. N.Engl.J.Med. 365: 2205-2219.
540. Smith, H. S., Bracken, D., and Smith, J. M. (2011). Pharmacotherapy for fibromyalgia. Front Pharmacol. 2: 17-
541. Julien, N., Goffaux, P., Arsenault, P., and Marchand, S. (2005). Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain. 114: 295-302.
542. Clauw, D. J., Arnold, L. M., and McCarberg, B. H. (2011). The science of fibromyalgia. Mayo Clin.Proc. 86: 907911.
543. Normand, E., Potvin, S., Gaumond, I., Cloutier, G. and others. (2011). Pain inhibition is deficient in chronic widespread pain but normal in major depressive disorder. J.Clin.Psychiatry. 72: 219-224.
544. Becker, S. and Schweinhardt, P. (2012). Dysfunctional neurotransmitter systems in fibromyalgia, their role in central stress circuitry and pharmacological actions on these systems. Pain Res.Treat. 2012: 741746-
545. de Souza, J. B., Potvin, S., Goffaux, P., Charest, J. and others. (2009). The deficit of pain inhibition in fibromyalgia is more pronounced in patients with comorbid depressive symptoms. Clin.J.Pain. 25: 123-127.
546. Wolfe, F., Clauw, D. J., Fitzcharles, M. A., Goldenberg, D. L. and others. (2010). The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res.(Hoboken.). 62: 600-610.
547. Idris, A. I., Sophocleous, A., Landao-Bassonga, E., Canals, M. and others. (2009). Cannabinoid receptor type 1 protects against age-related osteoporosis by regulating osteoblast and adipocyte differentiation in marrow stromal cells. Cell Metab. 10: 139-147.
548. Bab, I., Smoum, R., Bradshaw, H., and Mechoulam, R. (2011). Skeletal lipidomics: regulation of bone metabolism by fatty acid amide family. Br.J.Pharmacol. 163: 1441-1446.
549. Idris, A. I., van ‘t Hof, R. J., Greig, I. R., Ridge, S. A. and others. (2005). Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat.Med. 11: 774-779.
550. Whyte, L. S., Ford, L., Ridge, S. A., Cameron, G. A. and others. (2012). Cannabinoids and bone: endocannabinoids modulate human osteoclast function in vitro. Br.J.Pharmacol. 165: 2584-2597.
551. Tam, J., Ofek, O., Fride, E., Ledent, C. and others. (2006). Involvement of neuronal cannabinoid receptor CB1 in regulation of bone mass and bone remodeling. Mol.Pharmacol. 70: 786-792.
552. Tam, J., Trembovler, V., Di, Marzo, V, Petrosino, S. and others. (2008). The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling. FASEB J. 22: 285-294.
553. Rossi, F., Siniscalco, D., Luongo, L., De, Petrocellis L. and others. (2009). The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption. Bone. 44: 476-484.
554. Ofek, O., Karsak, M., Leclerc, N., Fogel, M. and others. (2006). Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc.Natl.Acad.Sci.U.S.A. 103: 696-701.
555. Sophocleous, A., Landao-Bassonga, E., van’t Hof, R. J., Idris, A. I. and others. (2011). The type 2 cannabinoid receptor regulates bone mass and ovariectomy-induced bone loss by affecting osteoblast differentiation and bone formation. Endocrinology. 152: 2141-2149.
556. Idris, A. I., Sophocleous, A., Landao-Bassonga, E., van’t Hof, R. J. and others. (2008). Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss by the type 2 cannabinoid receptor. Endocrinology. 149: 5619-5626.
557. Karsak, M., Cohen-Solal, M., Freudenberg, J., Ostertag, A. and others. (2005). Cannabinoid receptor type 2 gene is associated with human osteoporosis. Hum.Mol.Genet. 14: 3389-3396.
558. Karsak, M., Malkin, I., Toliat, M. R., Kubisch, C. and others. (2009). The cannabinoid receptor type 2 (CNR2) gene is associated with hand bone strength phenotypes in an ethnically homogeneous family sample. Hum.Genet. 126: 629-636.
559. Huang, Q. Y., Li, G. H., and Kung, A. W. (2009). Multiple osteoporosis susceptibility genes on chromosome 1p36 in Chinese. Bone. 44: 984-988.
560. Fernandez-Ruiz, J. (2009). The endocannabinoid system as a target for the treatment of motor dysfunction. Br.J.Pharmacol. 156: 1029-1040.
561. Glass, M., Dragunow, M., and Faull, R. L. (2000). The pattern of neurodegeneration in Huntington’s disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington’s disease. Neuroscience. 97: 505-519.
562. Romero, J., Berrendero, F., Perez-Rosado, A., Manzanares, J. and others. (2000). Unilateral 6-hydroxydopamine lesions of nigrostriatal dopaminergic neurons increased CB1 receptor mRNA levels in the caudateputamen. Life Sci. 66: 485-494.
563. Lastres-Becker, I., Fezza, F., Cebeira, M., Bisogno, T. and others. (2001). Changes in endocannabinoid transmission in the basal ganglia in a rat model of Huntington’s disease. Neuroreport. 12: 2125-2129.
564. Garcia-Arencibia, M., Garcia, C., and Fernandez-Ruiz, J. (2009). Cannabinoids and Parkinson’s disease. CNS.Neurol.Disord.Drug Targets. 8: 432-439.
565. Richter, A. and Loscher, W. (1994). (+)-WIN 55,212-2, a novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters. Eur.J.Pharmacol. 264: 371-377.
566. Richter, A. and Loscher, W. (2002). Effects of pharmacological manipulations of cannabinoid receptors on severity of dystonia in a genetic model of paroxysmal dyskinesia. Eur.J.Pharmacol. 454: 145-151.
567. Madsen, M. V., Peacock, L. P., Werge, T., Andersen, M. B. and others. (2011). Effects of cannabinoid CB(1) receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys. Neuropharmacology. 60: 418-422.
568. Uribe Roca, M. C., Micheli, F., and Viotti, R. (2005). Cannabis sativa and dystonia secondary to Wilson’s disease. Mov Disord. 20: 113-115.
569. Jabusch, H. C., Schneider, U., and Altenmuller, E. (2004). Delta9-tetrahydrocannabinol improves motor control in a patient with musician’s dystonia. Mov Disord. 19: 990-991.
570. Consroe, P., Sandyk, R., and Snider, S. R. (1986). Open label evaluation of cannabidiol in dystonic movement disorders. Int.J.Neurosci. 30: 277-282.
571. Fox, S. H., Kellett, M., Moore, A. P., Crossman, A. R. and others. (2002). Randomised, double-blind, placebocontrolled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Mov Disord. 17: 145-149.
572. Denovan-Wright, E. M. and Robertson, H. A. (2000). Cannabinoid receptor messenger RNA levels decrease in a subset of neurons of the lateral striatum, cortex and hippocampus of transgenic Huntington’s disease mice. Neuroscience. 98: 705-713.
573. Lastres-Becker, I., Gomez, M., de, Miguel R., Ramos, J. A. and others. (2002). Loss of cannabinoid CB(1) receptors in the basal ganglia in the late akinetic phase of rats with experimental Huntington’s disease. Neurotox.Res. 4: 601-608.
574. Naver, B., Stub, C., Moller, M., Fenger, K. and others. (2003). Molecular and behavioral analysis of the R6/1 Huntington’s disease transgenic mouse. Neuroscience. 122: 1049-1057.
575. McCaw, E. A., Hu, H., Gomez, G. T., Hebb, A. L. and others. (2004). Structure, expression and regulation of the cannabinoid receptor gene (CB1) in Huntington’s disease transgenic mice. Eur.J.Biochem. 271: 4909-4920.
576. Centonze, D., Rossi, S., Prosperetti, C., Tscherter, A. and others. (2005). Abnormal sensitivity to cannabinoid receptor stimulation might contribute to altered gamma-aminobutyric acid transmission in the striatum of R6/2 Huntington’s disease mice. Biol.Psychiatry. 57: 1583-1589.
577. Pazos, M. R., Sagredo, O., and Fernandez-Ruiz, J. (2008). The endocannabinoid system in Huntington’s disease. Curr.Pharm.Des. 14: 2317-2325.
578. Dowie, M. J., Bradshaw, H. B., Howard, M. L., Nicholson, L. F. and others. (2009). Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington’s disease. Neuroscience. 163: 456-465.
579. Blazquez, C., Chiarlone, A., Sagredo, O., Aguado, T. and others. (2011). Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington’s disease. Brain. 134: 119-136.
580. Casteels, C., Vandeputte, C., Rangarajan, J. R., Dresselaers, T. and others. (2011). Metabolic and type 1 cannabinoid receptor imaging of a transgenic rat model in the early phase of Huntington disease. Exp.Neurol. 229: 440449.
581. Mievis, S., Blum, D., and Ledent, C. (2011). Worsening of Huntington disease phenotype in CB1 receptor knockout mice. Neurobiol.Dis. 42: 524-529.
582. Van Laere K., Casteels, C., Dhollander, I., Goffin, K. and others. (2010). Widespread decrease of type 1 cannabinoid receptor availability in Huntington disease in vivo. J.Nucl.Med. 51: 1413-1417.
583. Palazuelos, J., Aguado, T., Pazos, M. R., Julien, B. and others. (2009). Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain. 132: 3152-3164.
584. Dowie, M. J., Howard, M. L., Nicholson, L. F., Faull, R. L. and others. (2010). Behavioural and molecular consequences of chronic cannabinoid treatment in Huntington’s disease transgenic mice. Neuroscience. 170: 324-336.
585. Consroe, P., Laguna, J., Allender, J., Snider, S. and others. (1991). Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol.Biochem.Behav. 40: 701-708.
586. Curtis, A., Mitchell, I., Patel, S., Ives, N. and others. (2009). A pilot study using nabilone for symptomatic treatment in Huntington’s disease. Mov Disord. 24: 2254-2259.
587. Muller-Vahl, K. R., Schneider, U., and Emrich, H. M. (1999). Nabilone increases choreatic movements in Huntington’s disease. Mov Disord. 14: 1038-1040.
588. Curtis, A. and Rickards, H. (2006). Nabilone could treat chorea and irritability in Huntington’s disease. J.Neuropsychiatry Clin.Neurosci. 18: 553-554.
589. Pisani, V., Moschella, V., Bari, M., Fezza, F. and others. (2010). Dynamic changes of anandamide in the cerebrospinal fluid of Parkinson’s disease patients. Mov Disord. 25: 920-924.
590. Pisani, A., Fezza, F., Galati, S., Battista, N. and others. (2005). High endogenous cannabinoid levels in the cerebrospinal fluid of untreated Parkinson’s disease patients. Ann.Neurol. 57: 777-779.
591. Garcia-Arencibia, M., Garcia, C., Kurz, A., Rodriguez-Navarro, J. A. and others. (2009). Cannabinoid CB1 receptors are early downregulated followed by a further upregulation in the basal ganglia of mice with deletion of specific park genes. J.Neural Transm.Suppl. 269-275.
592. Papa, S. M. (2008). The cannabinoid system in Parkinson’s disease: multiple targets to motor effects. Exp.Neurol. 211: 334-338.
593. Garcia, C., Palomo, C., Garcia-Arencibia, M., Ramos, J. A. and others. (2011). Symptom-relieving and neuroprotective effects of the phytocannabinoid D(9) -THCV in animal models of Parkinson’s disease. Br.J.Pharmacol. 163: 1495-1506.
594. Frankel, J. P., Hughes, A., Lees, A. J., and Stern, G. M. (1990). Marijuana for parkinsonian tremor. J.Neurol.Neurosurg.Psychiatry. 53: 436.-
595. Sieradzan, K. A., Fox, S. H., Hill, M., Dick, J. P. and others. (2001). Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: a pilot study. Neurology. 57: 2108-2111.
596. Carroll, C. B., Bain, P. G., Teare, L., Liu, X. and others. (2004). Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Neurology. 63: 1245-1250.
597. Sandyk, R. and Awerbuch, G. (1988). Marijuana and Tourette’s syndrome. J.Clin.Psychopharmacol. 8: 444-445.
598. Hemming, M. and Yellowlees, P. M. (1993). Effective treatment of Tourette’s syndrome with marijuana. Journal of Psychopharmacology. 7: 389-391.
599. Muller-Vahl, K. R., Koblenz, A., Jobges, M., Kolbe, H. and others. (2001). Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol (delta9-THC) on neuropsychological performance. Pharmacopsychiatry. 34: 19-24.
600. Muller-Vahl, K. R., Schneider, U., Prevedel, H., Theloe, K. and others. (2003). Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J.Clin.Psychiatry. 64: 459-465.
601. Curtis, A., Clarke, C. E., and Rickards, H. E. (2009). Cannabinoids for Tourette’s Syndrome. Cochrane.Database.Syst.Rev. CD006565.-
602. Cheung, W., Guo, L., and Cordeiro, M. F. (2008). Neuroprotection in glaucoma: drug-based approaches. Optom.Vis.Sci. 85: 406-416.
603. Jarvinen, T., Pate, D. W., and Laine, K. (2002). Cannabinoids in the treatment of glaucoma. Pharmacol.Ther. 95: 203-220.
604. Jampel, H. (2010). American glaucoma society position statement: marijuana and the treatment of glaucoma. J.Glaucoma. 19: 75-76.
605. Chen, J., Matias, I., Dinh, T., Lu, T. and others. (2005). Finding of endocannabinoids in human eye tissues: implications for glaucoma. Biochem.Biophys.Res.Commun. 330: 1062-1067.
606. Porcella, A., Casellas, P., Gessa, G. L., and Pani, L. (1998). Cannabinoid receptor CB1 mRNA is highly expressed in the rat ciliary body: implications for the antiglaucoma properties of marihuana. Brain Res.Mol.Brain Res. 58: 240-245.
607. Straiker, A. J., Maguire, G., Mackie, K., and Lindsey, J. (1999). Localization of cannabinoid CB1 receptors in the human anterior eye and retina. Invest Ophthalmol.Vis.Sci. 40: 2442-2448.
608. Porcella, A., Maxia, C., Gessa, G. L., and Pani, L. (2000). The human eye expresses high levels of CB1 cannabinoid receptor mRNA and protein. Eur.J.Neurosci. 12: 1123-1127.
609. Song, Z. H. and Slowey, C. A. (2000). Involvement of cannabinoid receptors in the intraocular pressure-lowering effects of WIN55212-2. J.Pharmacol.Exp.Ther. 292: 136-139.
610. Porcella, A., Maxia, C., Gessa, G. L., and Pani, L. (2001). The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies. Eur.J.Neurosci. 13: 409-412.
611. Flach, A. J. (2002). Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Trans.Am.Ophthalmol.Soc. 100: 215-222.
612. Yoles, E., Belkin, M., and Schwartz, M. (1996). HU-211, a nonpsychotropic cannabinoid, produces short- and longterm neuroprotection after optic nerve axotomy. J.Neurotrauma. 13: 49-57.
613. Shen, M. and Thayer, S. A. (1998). Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity. Mol.Pharmacol. 54: 459-462.
614. Levin, L. A. (1999). Direct and indirect approaches to neuroprotective therapy of glaucomatous optic neuropathy. Surv.Ophthalmol. 43 Suppl 1: S98-101.
615. Jin, K. L., Mao, X. O., Goldsmith, P. C., and Greenberg, D. A. (2000). CB1 cannabinoid receptor induction in experimental stroke. Ann.Neurol. 48: 257-261.
616. Panikashvili, D., Simeonidou, C., Ben-Shabat, S., Hanus, L. and others. (2001). An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature. 413: 527-531.
617. Marsicano, G., Moosmann, B., Hermann, H., Lutz, B. and others. (2002). Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1. J.Neurochem. 80: 448-456.
618. Mechoulam, R., Panikashvili, D., and Shohami, E. (2002). Cannabinoids and brain injury: therapeutic implications. Trends Mol.Med. 8: 58-61.
619. Braida, D., Pegorini, S., Arcidiacono, M. V., Consalez, G. G. and others. (2003). Post-ischemic treatment with cannabidiol prevents electroencephalographic flattening, hyperlocomotion and neuronal injury in gerbils. Neurosci.Lett. 346: 61-64.
620. El-Remessy, A. B., Al-Shabrawey, M., Khalifa, Y., Tsai, N. T. and others. (2006). Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes. Am.J.Pathol. 168: 235-244.
621. Gilbert, G. L., Kim, H. J., Waataja, J. J., and Thayer, S. A. (2007). Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity. Brain Res. 1128: 61-69.
622. Wan, M. J., Daniel, S., Kassam, F., Mutti, G. and others. (2012). Survey of complementary and alternative medicine use in glaucoma patients. J.Glaucoma. 21: 79-82.
623. Hepler, R. S. and Frank, I. R. (1971). Marihuana smoking and intraocular pressure. JAMA. 217: 1392.-
624. Merritt, J. C., Crawford, W. J., Alexander, P. C., Anduze, A. L. and others. (1980). Effect of marihuana on intraocular and blood pressure in glaucoma. Ophthalmology. 87: 222-228.
625. Zhan, G. L., Camras, C. B., Palmberg, P. F., and Toris, C. B. (2005). Effects of marijuana on aqueous humor dynamics in a glaucoma patient. J.Glaucoma. 14: 175-177.
626. Abboud, R. T. and Sanders, H. D. (1976). Effect of oral administration of delta-tetrahydrocannabinol on airway mechanics in normal and asthmatic subjects. Chest. 70: 480-485.
627. Calignano, A., Katona, I., Desarnaud, F., Giuffrida, A. and others. (2000). Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature. 408: 96-101.
628. Jan, T. R., Farraj, A. K., Harkema, J. R., and Kaminski, N. E. (2003). Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatment in A/J mice. Toxicol.Appl.Pharmacol. 188: 24-35.
629. Giannini, L., Nistri, S., Mastroianni, R., Cinci, L. and others. (2008). Activation of cannabinoid receptors prevents antigen-induced asthma-like reaction in guinea pigs. J.Cell Mol.Med. 12: 2381-2394.
630. Fukuda, H., Abe, T., and Yoshihara, S. (2010). The cannabinoid receptor agonist WIN 55,212-2 inhibits antigeninduced plasma extravasation in guinea pig airways. Int.Arch.Allergy Immunol. 152: 295-300.
631. Vachon, L., FitzGerald, M. X., Solliday, N. H., Gould, I. A. and others. (1973). Single-dose effects of marihuana smoke. Bronchial dynamics and respiratory-center sensitivity in normal subjects. N.Engl.J.Med. 288: 985989.
632. Tashkin, D. P., Shapiro, B. J., and Frank, I. M. (1973). Acute pulmonary physiologic effects of smoked marijuana and oral 9 -tetrahydrocannabinol in healthy young men. N.Engl.J.Med. 289: 336-341.
633. Tashkin, D. P. (2001). Airway effects of marijuana, cocaine, and other inhaled illicit agents. Curr.Opin.Pulm.Med. 7: 43-61.
634. Tashkin, D. P., Shapiro, B. J., and Frank, I. M. (1974). Acute effects of smoked marijuana and oral delta9tetrahydrocannabinol on specific airway conductance in asthmatic subjects. Am.Rev.Respir.Dis. 109: 420428.
635. Tashkin, D. P., Shapiro, B. J., Lee, Y. E., and Harper, C. E. (1975). Effects of smoked marijuana in experimentally induced asthma. Am.Rev.Respir.Dis. 112: 377-386.
636. Gong, H., Jr., Tashkin, D. P., Simmons, M. S., Calvarese, B. and others. (1984). Acute and subacute bronchial effects of oral cannabinoids. Clin.Pharmacol.Ther. 35: 26-32.
637. Williams, S. J., Hartley, J. P., and Graham, J. D. (1976). Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. Thorax. 31: 720-723.
638. Hartley, J. P., Nogrady, S. G., and Seaton, A. (1978). Bronchodilator effect of delta1-tetrahydrocannabinol. Br.J.Clin.Pharmacol. 5: 523-525.
639. Tashkin, D. P., Shapiro, B. J., Lee, Y. E., and Harper, C. E. (1976). Subacute effects of heavy marihuana smoking on pulmonary function in healthy men. N.Engl.J.Med. 294: 125-129.
640. Davies, B. H., Radcliffe, S., Seaton, A., and Graham, J. D. (1975). A trial of oral delta-1-(trans)tetrahydrocannabinol in reversible airways obstruction. Thorax. 30: 80-85.
641. Gong, H., Jr., Tashkin, D. P., and Calvarese, B. (1983). Comparison of bronchial effects of nabilone and terbutaline in healthy and asthmatic subjects. J.Clin.Pharmacol. 23: 127-133.
642. Pacher, P., Batkai, S., and Kunos, G. (2005). Cardiovascular pharmacology of cannabinoids. Handb.Exp.Pharmacol. 599-625.
643. Crawford, W. J. and Merritt, J. C. (1979). Effects of tetrahydrocannabinol on arterial and intraocular hypertension. Int.J.Clin.Pharmacol.Biopharm. 17: 191-196.
644. Denson, T. F. and Earleywine, M. (2006). Decreased depression in marijuana users. Addict.Behav. 31: 738-742.
645. Witkin, J. M., Tzavara, E. T., and Nomikos, G. G. (2005). A role for cannabinoid CB1 receptors in mood and anxiety disorders. Behav.Pharmacol. 16: 315-331.
646. Moreira, F. A. and Wotjak, C. T. (2010). Cannabinoids and anxiety. Curr.Top.Behav.Neurosci. 2: 429-450.
647. Bambico, F. R., Katz, N., Debonnel, G., and Gobbi, G. (2007). Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex. J.Neurosci. 27: 11700-11711.
648. Bambico, F. R. and Gobbi, G. (2008). The cannabinoid CB1 receptor and the endocannabinoid anandamide: possible antidepressant targets. Expert.Opin.Ther.Targets. 12: 1347-1366.
649. Hill, M. N. and Gorzalka, B. B. (2005). Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the rat forced swim test. Eur.Neuropsychopharmacol. 15: 593-599.
650. Christensen, R., Kristensen, P. K., Bartels, E. M., Bliddal, H. and others. (2007). Efficacy and safety of the weightloss drug rimonabant: a meta-analysis of randomised trials. Lancet. 370: 1706-1713.
651. Gorzalka, B. B. and Hill, M. N. (2010). Putative role of endocannabinoid signaling in the etiology of depression and actions of antidepressants. Prog.Neuropsychopharmacol.Biol.Psychiatry. 35: 1575-1585.
652. Hill, M. N., Miller, G. E., Carrier, E. J., Gorzalka, B. B. and others. (2009). Circulating endocannabinoids and Nacyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology. 34: 1257-1262.
653. Woolridge, E., Barton, S., Samuel, J., Osorio, J. and others. (2005). Cannabis use in HIV for pain and other medical symptoms. J.Pain Symptom.Manage. 29: 358-367.
654. Page, S. A. and Verhoef, M. J. (2006). Medicinal marijuana use: experiences of people with multiple sclerosis. Can.Fam.Physician. 52: 64-65.
655. Mitchell, P. B. and Morris, M. J. (2007). Depression and anxiety with rimonabant. Lancet. 370: 1671-1672.
656. Morgan, C. J., Schafer, G., Freeman, T. P., and Curran, H. V. (2010). Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: naturalistic study [corrected]. Br.J.Psychiatry. 197: 285-290.
657. Guimaraes, F. S., de Aguiar, J. C., Mechoulam, R., and Breuer, A. (1994). Anxiolytic effect of cannabidiol derivatives in the elevated plus-maze. Gen.Pharmacol. 25: 161-164.
658. Crippa, J. A., Zuardi, A. W., Garrido, G. E., Wichert-Ana, L. and others. (2004). Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology. 29: 417-426.
659. Bergamaschi, M. M., Queiroz, R. H., Chagas, M. H., de Oliveira, D. C. and others. (2011). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 36: 1219-1226.
660. Resstel, L. B., Tavares, R. F., Lisboa, S. F., Joca, S. R. and others. (2009). 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br.J.Pharmacol. 156: 181-188.
661. Gomes, F. V., Resstel, L. B., and Guimaraes, F. S. (2011). The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Psychopharmacology (Berl). 213: 465-473.
662. Koethe, D., Schreiber, D., Giuffrida, A., Mauss, C. and others. (2009). Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid. J.Neural Transm. 116: 301-305.
663. Herrera-Solis, A., Vasquez, K. G., and Prospero-Garcia, O. (2010). Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats. Pharmacol.Biochem.Behav. 95: 106-112.
664. Bolla, K. I., Lesage, S. R., Gamaldo, C. E., Neubauer, D. N. and others. (2008). Sleep disturbance in heavy marijuana users. Sleep. 31: 901-908.
665. Bolla, K. I., Lesage, S. R., Gamaldo, C. E., Neubauer, D. N. and others. (2010). Polysomnogram changes in marijuana users who report sleep disturbances during prior abstinence. Sleep Med. 11: 882-889.
666. Lutz, B. (2007). The endocannabinoid system and extinction learning. Mol.Neurobiol. 36: 92-101.
667. Pamplona, F. A., Prediger, R. D., Pandolfo, P., and Takahashi, R. N. (2006). The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory in rats. Psychopharmacology (Berl). 188: 641-649.
668. Marsicano, G., Wotjak, C. T., Azad, S. C., Bisogno, T. and others. (2002). The endogenous cannabinoid system controls extinction of aversive memories. Nature. 418: 530-534.
669. Varvel, S. A. and Lichtman, A. H. (2002). Evaluation of CB1 receptor knockout mice in the Morris water maze. J.Pharmacol.Exp.Ther. 301: 915-924.
670. Chhatwal, J. P., Davis, M., Maguschak, K. A., and Ressler, K. J. (2005). Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Neuropsychopharmacology. 30: 516-524.
671. Pava, M. J. and Woodward, J. J. (2012). A review of the interactions between alcohol and the endocannabinoid system: implications for alcohol dependence and future directions for research. Alcohol. 46: 185-204.
672. Deikel, S. M. and Carder, B. (1976). Attentuation of precipitated abstinence in methadone-dependent rats by delta9THC. Psychopharmacol.Commun. 2: 61-65.
673. Vela, G., Fuentes, J. A., Bonnin, A., Fernandez-Ruiz, J. and others. (1995). Perinatal exposure to delta 9tetrahydrocannabinol (delta 9-THC) leads to changes in opioid-related behavioral patterns in rats. Brain Res. 680: 142-147.
674. Yamaguchi, T., Hagiwara, Y., Tanaka, H., Sugiura, T. and others. (2001). Endogenous cannabinoid, 2arachidonoylglycerol, attenuates naloxone-precipitated withdrawal signs in morphine-dependent mice. Brain Res. 909: 121-126.
675. Reiman, A. (2009). Cannabis as a substitute for alcohol and other drugs. Harm.Reduct.J. 6: 35-39.
676. Fernandez-Espejo, E., Viveros, M. P., Nunez, L., Ellenbroek, B. A. and others. (2009). Role of cannabis and endocannabinoids in the genesis of schizophrenia. Psychopharmacology (Berl). 206: 531-549.
677. Koethe, D., Giuffrida, A., Schreiber, D., Hellmich, M. and others. (2009). Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. Br.J.Psychiatry. 194: 371-372.
678. Leweke, F. M., Giuffrida, A., Wurster, U., Emrich, H. M. and others. (1999). Elevated endogenous cannabinoids in schizophrenia. Neuroreport. 10: 1665-1669.
679. De Marchi, N., De Petrocellis, L., Orlando, P., Daniele, F. and others. (2003). Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids Health Dis. 2: 5.-
680. Rodriguez de Fonseca, F., Gorriti, M. A., Bilbao, A., Escuredo, L. and others. (2001). Role of the endogenous cannabinoid system as a modulator of dopamine transmission: implications for Parkinson’s disease and schizophrenia. Neurotox.Res. 3: 23-35.
681. McCreadie, R. G. (2002). Use of drugs, alcohol and tobacco by people with schizophrenia: case-control study. Br.J.Psychiatry. 181: 321-325.
682. Gregg, L., Barrowclough, C., and Haddock, G. (2007). Reasons for increased substance use in psychosis. Clin.Psychol.Rev. 27: 494-510.
683. Khantzian, E. J. (1985). The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am.J.Psychiatry. 142: 1259-1264.
684. Lembke, A. (2012). Time to abandon the self-medication hypothesis in patients with psychiatric disorders. Am.J.Drug Alcohol Abuse. 38: 524-529.
685. Chambers, R. A., Krystal, J. H., and Self, D. W. (2001). A neurobiological basis for substance abuse comorbidity in schizophrenia. Biol.Psychiatry. 50: 71-83.
686. Caspi, A., Moffitt, T. E., Cannon, M., McClay, J. and others. (2005). Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol.Psychiatry. 57: 1117-1127.
687. Henquet, C., Rosa, A., Krabbendam, L., Papiol, S. and others. (2006). An experimental study of catechol-omethyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology. 31: 2748-2757.
688. Henquet, C., Rosa, A., Delespaul, P., Papiol, S. and others. (2009). COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of ‘switching on’ hallucinations in the flow of daily life. Acta Psychiatr.Scand. 119: 156-160.
689. Pelayo-Teran, J. M., Perez-Iglesias, R., Mata, I., Carrasco-Marin, E. and others. (2010). Catechol-OMethyltransferase (COMT) Val158Met variations and cannabis use in first-episode non-affective psychosis: clinical-onset implications. Psychiatry Res. 179: 291-296.
690. Estrada, G., Fatjo-Vilas, M., Munoz, M. J., Pulido, G. and others. (2011). Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism. Acta Psychiatr.Scand. 123: 485-492.
691. van Winkel, R., van Beveren, N. J., and Simons, C. (2011). AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder. Neuropsychopharmacology. 36: 2529-2537.
692. van Winkel, R. (2011). Family-based analysis of genetic variation underlying psychosis-inducing effects of cannabis: sibling analysis and proband follow-up. Arch.Gen.Psychiatry. 68: 148-157.
693. Di Forti, M., Iyegbe, C., Sallis, H., Kolliakou, A. and others. (2012). Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users. Biol.Psychiatry. 72: 811-816.
694. Leweke, F. M., Schneider, U., Radwan, M., Schmidt, E. and others. (2000). Different effects of nabilone and cannabidiol on binocular depth inversion in Man. Pharmacol.Biochem.Behav. 66: 175-181.
695. Musty, R. Cannabinoids and anxiety. Cannabinoids as Therapeutics. Mechoulam, R. Basel: Birkhaüser, 2005.
696. Zuardi, A. W., Rodrigues, J. A., and Cunha, J. M. (1991). Effects of cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology (Berl). 104: 260-264.
697. Moreira, F. A. and Guimaraes, F. S. (2005). Cannabidiol inhibits the hyperlocomotion induced by psychotomimetic drugs in mice. Eur.J.Pharmacol. 512: 199-205.
698. Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D. and others. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl.Psychiatry. 2: e94-
699. Zuardi, A. W. (2008). Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev.Bras.Psiquiatr. 30: 271-280.
700. Benito, C., Nunez, E., Pazos, M. R., Tolon, R. M. and others. (2007). The endocannabinoid system and Alzheimer’s disease. Mol.Neurobiol. 36: 75-81.
701. Koppel, J. and Davies, P. (2008). Targeting the endocannabinoid system in Alzheimer’s disease. J.Alzheimers.Dis. 15: 495-504.
702. van der Stelt, M., Mazzola, C., Esposito, G., Matias, I. and others. (2006). Endocannabinoids and beta-amyloidinduced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels. Cell Mol.Life Sci. 63: 1410-1424.
703. Jung, K. M., Astarita, G., Yasar, S., Vasilevko, V. and others. (2011). An amyloid beta(42)-dependent deficit in anandamide mobilization is associated with cognitive dysfunction in Alzheimer’s disease. Neurobiol.Aging. 33: 1522-1532.
704. Noonan, J., Tanveer, R., Klompas, A., Gowran, A. and others. (2010). Endocannabinoids prevent beta-amyloidmediated lysosomal destabilization in cultured neurons. J.Biol.Chem. 285: 38543-38554.
705. Eubanks, L. M., Rogers, C. J., Beuscher, A. E., Koob, G. F. and others. (2006). A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Mol.Pharm. 3: 773-777.
706. Iuvone, T., Esposito, G., Esposito, R., Santamaria, R. and others. (2004). Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. J.Neurochem. 89: 134-141.
707. Esposito, G., De, Filippis D., Carnuccio, R., Izzo, A. A. and others. (2006). The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells. J.Mol.Med.(Berl). 84: 253-258.
708. Booz, G. W. (2011). Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic.Biol.Med. 51: 1054-1061.
709. Esposito, G., Scuderi, C., Savani, C., Steardo, L., Jr. and others. (2007). Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. Br.J.Pharmacol. 151: 12721279.
710. Esposito, G., Iuvone, T., Savani, C., Scuderi, C. and others. (2007). Opposing control of cannabinoid receptor stimulation on amyloid-beta-induced reactive gliosis: in vitro and in vivo evidence. J.Pharmacol.Exp.Ther. 322: 1144-1152.
711. Walther, S., Mahlberg, R., Eichmann, U., and Kunz, D. (2006). Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology (Berl). 185: 524-528.
712. Passmore, M. J. (2008). The cannabinoid receptor agonist nabilone for the treatment of dementia-related agitation. Int.J.Geriatr.Psychiatry. 23: 116-117.
713. Krishnan, S., Cairns, R., and Howard, R. (2009). Cannabinoids for the treatment of dementia. Cochrane.Database.Syst.Rev. CD007204.-
714. Klein, T. W. (2005). Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat.Rev.Immunol. 5: 400-411.
715. Nagarkatti, P., Pandey, R., Rieder, S. A., Hegde, V. L. and others. (2009). Cannabinoids as novel anti-inflammatory drugs. Future.Med.Chem. 1: 1333-1349.
716. Stander, S., Schmelz, M., Metze, D., Luger, T. and others. (2005). Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J.Dermatol.Sci. 38: 177-188.
717. Toth, B. I., Dobrosi, N., Dajnoki, A., Czifra, G. and others. (2011). Endocannabinoids modulate human epidermal keratinocyte proliferation and survival via the sequential engagement of cannabinoid receptor-1 and transient receptor potential vanilloid-1. J.Invest Dermatol. 131: 1095-1104.
718. Maccarrone, M., Di Rienzo M., Battista, N., Gasperi, V. and others. (2003). The endocannabinoid system in human keratinocytes. Evidence that anandamide inhibits epidermal differentiation through CB1 receptordependent inhibition of protein kinase C, activation protein-1, and transglutaminase. J.Biol.Chem. 278: 33896-33903.
719. Wilkinson, J. D. and Williamson, E. M. (2007). Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J.Dermatol.Sci. 45: 87-92.
720. Dvorak, M., Watkinson, A., McGlone, F., and Rukwied, R. (2003). Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin. Inflamm.Res. 52: 238-245.
721. Rukwied, R., Watkinson, A., McGlone, F., and Dvorak, M. (2003). Cannabinoid agonists attenuate capsaicininduced responses in human skin. Pain. 102: 283-288.
722. Watson, E. S., Murphy, J. C., and Turner, C. E. (1983). Allergenic properties of naturally occurring cannabinoids. J.Pharm.Sci. 72: 954-955.
723. Williams, C., Thompstone, J., and Wilkinson, M. (2008). Work-related contact urticaria to Cannabis sativa. Contact Dermatitis. 58: 62-63.
724. Mikuriya, T. H. (1969). Marijuana in medicine: past, present and future. Calif.Med. 110: 34-40.
725. Kalant, H. (2001). Medicinal use of cannabis: history and current status. Pain Res.Manag. 6: 80-91.
726. Zuardi, A. W. (2006). History of cannabis as a medicine: a review. Rev.Bras.Psiquiatr. 28: 153-157.
727. Duncan, M., Thomas, A. D., Cluny, N. L., Patel, A. and others. (2008). Distribution and function of monoacylglycerol lipase in the gastrointestinal tract. Am.J.Physiol Gastrointest.Liver Physiol. 295: G1255G1265.
728. Kennedy, P. J., Clarke, G., Quigley, E. M., Groeger, J. A. and others. (2012). Gut memories: towards a cognitive neurobiology of irritable bowel syndrome. Neurosci.Biobehav.Rev. 36: 310-340.
729. Storr, M. A., Yuce, B., Andrews, C. N., and Sharkey, K. A. (2008). The role of the endocannabinoid system in the pathophysiology and treatment of irritable bowel syndrome. Neurogastroenterol.Motil. 20: 857-868.
730. Yao, X., Yang, Y. S., Cui, L. H., Zhao, K. B. and others. (2012). Subtypes of irritable bowel syndrome on Rome III criteria: a multicenter study. J.Gastroenterol.Hepatol. 27: 760-765.
731. Camilleri, M., Carlson, P., McKinzie, S., Grudell, A. and others. (2008). Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation. Am.J.Physiol Gastrointest.Liver Physiol. 294: G13G19.
732. Park, J. M., Choi, M. G., Cho, Y. K., Lee, I. S. and others. (2011). Cannabinoid receptor 1 gene polymorphism and irritable bowel syndrome in the Korean population: a hypothesis-generating study. J.Clin.Gastroenterol. 45: 45-49.
733. Camilleri, M. and Katzka, D. A. (2012). Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome. Am.J.Physiol Gastrointest.Liver Physiol. 302: G1075-G1084.
734. Sanson, M., Bueno, L., and Fioramonti, J. (2006). Involvement of cannabinoid receptors in inflammatory hypersensitivity to colonic distension in rats. Neurogastroenterol.Motil. 18: 949-956.
735. Brusberg, M., Arvidsson, S., Kang, D., Larsson, H. and others. (2009). CB1 receptors mediate the analgesic effects of cannabinoids on colorectal distension-induced visceral pain in rodents. J.Neurosci. 29: 1554-1564.
736. Kimball, E. S., Wallace, N. H., Schneider, C. R., D’Andrea, M. R. and others. (2010). Small intestinal cannabinoid receptor changes following a single colonic insult with oil of mustard in mice. Front Pharmacol. 1: 132-
737. Esfandyari, T., Camilleri, M., Ferber, I., Burton, D. and others. (2006). Effect of a cannabinoid agonist on gastrointestinal transit and postprandial satiation in healthy human subjects: a randomized, placebocontrolled study. Neurogastroenterol.Motil. 18: 831-838.
738. Esfandyari, T., Camilleri, M., Busciglio, I., Burton, D. and others. (2007). Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study. Am.J.Physiol Gastrointest.Liver Physiol. 293: G137-G145.
739. Rao, S. S. and Singh, S. (2010). Clinical utility of colonic and anorectal manometry in chronic constipation. J.Clin.Gastroenterol. 44: 597-609.
740. Coulie, B., Camilleri, M., Bharucha, A. E., Sandborn, W. J. and others. (2001). Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects. Aliment.Pharmacol.Ther. 15: 653-663.
741. Lembo, T., Wright, R. A., Bagby, B., Decker, C. and others. (2001). Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. Am.J.Gastroenterol. 96: 2662-2670.
742. Wong, B. S., Camilleri, M., Busciglio, I., Carlson, P. and others. (2011). Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome. Gastroenterology. 141: 1638-1647.
743. Wong, B. S., Camilleri, M., Eckert, D., Carlson, P. and others. (2012). Randomized pharmacodynamic and pharmacogenetic trial of dronabinol effects on colon transit in irritable bowel syndrome-diarrhea. Neurogastroenterol.Motil. 24: 358-e169.
744. Di Sabatino, A., Battista, N., Biancheri, P., Rapino, C. and others. (2011). The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease. Mucosal.Immunol. 4: 574-583.
745. Mowat, C., Cole, A., Windsor, A., Ahmad, T. and others. (2011). Guidelines for the management of inflammatory bowel disease in adults. Gut. 60: 571-607.
746. Ligresti, A., Bisogno, T., Matias, I., De, Petrocellis L. and others. (2003). Possible endocannabinoid control of colorectal cancer growth. Gastroenterology. 125: 677-687.
747. Guagnini, F., Valenti, M., Mukenge, S., Matias, I. and others. (2006). Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P. Gut. 55: 946-953.
748. D’Argenio, G., Petrosino, S., Gianfrani, C., Valenti, M. and others. (2007). Overactivity of the intestinal endocannabinoid system in celiac disease and in methotrexate-treated rats. J.Mol.Med. 85: 523-530.
749. Massa, F., Marsicano, G., Hermann, H., Cannich, A. and others. (2004). The endogenous cannabinoid system protects against colonic inflammation. J.Clin.Invest. 113: 1202-1209.
750. D’Argenio, G., Valenti, M., Scaglione, G., Cosenza, V. and others. (2006). Up-regulation of anandamide levels as an endogenous mechanism and a pharmacological strategy to limit colon inflammation. FASEB J. 20: 568570.
751. Kimball, E. S., Schneider, C. R., Wallace, N. H., and Hornby, P. J. (2006). Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium. Am.J.Physiol Gastrointest.Liver Physiol. 291: G364-G371.
752. Storr, M., Emmerdinger, D., Diegelmann, J., Yuce, B. and others. (2009). The role of fatty acid hydrolase gene variants in inflammatory bowel disease. Aliment.Pharmacol.Ther. 29: 542-551.
753. Engel, M. A., Kellermann, C. A., Burnat, G., Hahn, E. G. and others. (2010). Mice lacking cannabinoid CB1-, CB2receptors or both receptors show increased susceptibility to trinitrobenzene sulfonic acid (TNBS)-induced colitis. J.Physiol Pharmacol. 61: 89-97.
754. Jamontt, J. M., Molleman, A., Pertwee, R. G., and Parsons, M. E. (2010). The effects of Delta-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis. Br.J.Pharmacol. 160: 712-723.
755. Di Paola, R., Mazzon, E., Patel, N. S., Genovese, T. and others. (2005). Beneficial effects of GW274150 treatment on the development of experimental colitis induced by dinitrobenzene sulfonic acid. Eur.J.Pharmacol. 507: 281-289.
756. Storr, M. A., Keenan, C. M., Zhang, H., Patel, K. D. and others. (2009). Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitis. Inflamm.Bowel.Dis. 15: 1678-1685.
757. Borrelli, F., Aviello, G., Romano, B., Orlando, P. and others. (2009). Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis. J.Mol.Med.(Berl). 87: 1111-1121.
758. Schicho, R. and Storr, M. (2012). Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology. 89: 149-155.
759. Alhouayek, M., Lambert, D. M., Delzenne, N. M., Cani, P. D. and others. (2011). Increasing endogenous 2arachidonoylglycerol levels counteracts colitis and related systemic inflammation. FASEB J. 25: 27112721.
760. Singh, U. P., Singh, N. P., Singh, B., Price, R. L. and others. (2012). Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10(-/-) mice by attenuating the activation of T cells and promoting their apoptosis. Toxicol.Appl.Pharmacol. 258: 256-267.
761. Izzo, A. A., Capasso, R., Aviello, G., Borrelli, F. and others. (2012). Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. Br.J.Pharmacol. 166: 1444-1460.
762. Klooker, T. K., Leliefeld, K. E., van den Wijngaard, R. M., and Boeckxstaens, G. E. (2011). The cannabinoid receptor agonist delta-9-tetrahydrocannabinol does not affect visceral sensitivity to rectal distension in healthy volunteers and IBS patients. Neurogastroenterol.Motil. 23: 30-5, e2.
763. Tam, J., Liu, J., Mukhopadhyay, B., Cinar, R. and others. (2011). Endocannabinoids in liver disease. Hepatology. 53: 346-355.
764. Teixeira-Clerc, F., Belot, M. P., Manin, S., Deveaux, V. and others. (2010). Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration. Hepatology. 52: 1046-1059.
765. Giannone, F. A., Baldassarre, M., Domenicali, M., Zaccherini, G. and others. (2012). Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl(4)-induced advanced cirrhosis. Lab Invest. 92: 384-395.
766. Lim, M. P., Devi, L. A., and Rozenfeld, R. (2011). Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis. Cell Death.Dis. 2: e170-
767. Mukhopadhyay, P., Rajesh, M., Horvath, B., Batkai, S. and others. (2011). Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radic.Biol.Med. 50: 1368-1381.
768. Fouad, A. A. and Jresat, I. (2011). Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats. Eur.J.Pharmacol. 670: 216-223.
769. Avraham, Y., Grigoriadis, N., Poutahidis, T., Vorobiev, L. and others. (2011). Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. Br.J.Pharmacol. 162: 1650-1658.
770. Batkai, S., Mukhopadhyay, P., Horvath, B., Rajesh, M. and others. (2012). Delta8-Tetrahydrocannabivarin prevents hepatic ischaemia/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors. Br.J.Pharmacol. 165: 2450-2461.
771. Silvestri, C., Ligresti, A., and Di, Marzo, V. (2011). Peripheral effects of the endocannabinoid system in energy homeostasis: adipose tissue, liver and skeletal muscle. Rev.Endocr.Metab Disord. 12: 153-162.
772. O’Hare, J. D., Zielinski, E., Cheng, B., Scherer, T. and others. (2011). Central endocannabinoid signaling regulates hepatic glucose production and systemic lipolysis. Diabetes. 60: 1055-1062.
773. Engeli, S. (2012). Central and peripheral cannabinoid receptors as therapeutic targets in the control of food intake and body weight. Handb.Exp.Pharmacol. 357-381.
774. Li, C., Jones, P. M., and Persaud, S. J. (2011). Role of the endocannabinoid system in food intake, energy homeostasis and regulation of the endocrine pancreas. Pharmacol.Ther. 129: 307-320.
775. Osei-Hyiaman, D., Depetrillo, M., Pacher, P., Liu, J. and others. (2005). Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J.Clin.Invest. 115: 12981305.
776. Pagano, C., Pilon, C., Calcagno, A., Urbanet, R. and others. (2007). The endogenous cannabinoid system stimulates glucose uptake in human fat cells via phosphatidylinositol 3-kinase and calcium-dependent mechanisms. J.Clin.Endocrinol.Metab. 92: 4810-4819.
777. Cardinal, P., Bellocchio, L., Clark, S., Cannich, A. and others. (2012). Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice. Endocrinology. 153: 4136-4143.
778. Cota, D., Marsicano, G., Tschop, M., Grubler, Y. and others. (2003). The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J.Clin.Invest. 112: 423-431.
779. Quarta, C., Bellocchio, L., Mancini, G., Mazza, R. and others. (2010). CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance. Cell Metab. 11: 273-285.
780. Osei-Hyiaman, D., Liu, J., Zhou, L., Godlewski, G. and others. (2008). Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J.Clin.Invest. 118: 3160-3169.
781. Liu, J., Zhou, L., Xiong, K., Godlewski, G. and others. (2012). Hepatic cannabinoid receptor-1 mediates diet-induced insulin resistance via inhibition of insulin signaling and clearance in mice. Gastroenterology. 142: 12181228.
782. Ravinet, Trillou C., Arnone, M., Delgorge, C., Gonalons, N. and others. (2003). Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am.J.Physiol Regul.Integr.Comp Physiol. 284: R345-R353.
783. Poirier, B., Bidouard, J. P., Cadrouvele, C., Marniquet, X. and others. (2005). The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. Diabetes Obes.Metab. 7: 65-72.
784. Jbilo, O., Ravinet-Trillou, C., Arnone, M., Buisson, I. and others. (2005). The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. FASEB J. 19: 1567-1569.
785. Watanabe, T., Kubota, N., Ohsugi, M., Kubota, T. and others. (2009). Rimonabant ameliorates insulin resistance via both adiponectin-dependent and adiponectin-independent pathways. J.Biol.Chem. 284: 1803-1812.
786. Jourdan, T., Djaouti, L., Demizieux, L., Gresti, J. and others. (2010). CB1 antagonism exerts specific molecular effects on visceral and subcutaneous fat and reverses liver steatosis in diet-induced obese mice. Diabetes. 59: 926-934.
787. Crespillo, A., Suarez, J., Bermudez-Silva, F. J., Rivera, P. and others. (2011). Expression of the cannabinoid system in muscle: effects of a high-fat diet and CB1 receptor blockade. Biochem.J. 433: 175-185.
788. Bell-Anderson, K. S., Aouad, L., Williams, H., Sanz, F. R. and others. (2011). Coordinated improvement in glucose tolerance, liver steatosis and obesity-associated inflammation by cannabinoid 1 receptor antagonism in fat Aussie mice. Int.J.Obes.(Lond). 35: 1539-1548.
789. Van Gaal, L. F., Rissanen, A. M., Scheen, A. J., Ziegler, O. and others. (2005). Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 365: 1389-1397.
790. Despres, J. P., Golay, A., and Sjostrom, L. (2005). Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N.Engl.J.Med. 353: 2121-2134.
791. Pi-Sunyer, F. X., Aronne, L. J., Heshmati, H. M., Devin, J. and others. (2006). Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA. 295: 761-775.
792. Scheen, A. J., Finer, N., Hollander, P., Jensen, M. D. and others. (2006). Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet. 368: 1660-1672.
793. Van Gaal, L. F., Scheen, A. J., Rissanen, A. M., Rossner, S. and others. (2008). Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors: two year results from the RIO-Europe Study. Eur.Heart J. 29: 1761-1771.
794. Van Gaal, L., Pi-Sunyer, X., Despres, J. P., McCarthy, C. and others. (2008). Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care. 31 Suppl 2: S229-S240.
795. Despres, J. P., Ross, R., Boka, G., Almeras, N. and others. (2009). Effect of rimonabant on the high-triglyceride/ low-HDL-cholesterol dyslipidemia, intraabdominal adiposity, and liver fat: the ADAGIO-Lipids trial. Arterioscler.Thromb.Vasc.Biol. 29: 416-423.
796. Hayatbakhsh, M. R., O’Callaghan, M. J., Mamun, A. A., Williams, G. M. and others. (2010). Cannabis use and obesity and young adults. Am.J.Drug Alcohol Abuse. 36: 350-356.
797. Le Strat, Y. and Le Foll, B. (2011). Obesity and cannabis use: results from 2 representative national surveys. Am.J.Epidemiol. 174: 929-933.
798. Deveaux, V., Cadoudal, T., Ichigotani, Y., Teixeira-Clerc, F. and others. (2009). Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis. PLoS.One. 4: e5844-
799. Agudo, J., Martin, M., Roca, C., Molas, M. and others. (2010). Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age. Diabetologia. 53: 2629-2640.
800. Levendal, R. A., Schumann, D., Donath, M., and Frost, C. L. (2012). Cannabis exposure associated with weight reduction and beta-cell protection in an obese rat model. Phytomedicine. 19: 575-582.
801. Li, C., Bowe, J. E., Huang, G. C., Amiel, S. A. and others. (2011). Cannabinoid receptor agonists and antagonists stimulate insulin secretion from isolated human islets of Langerhans. Diabetes Obes.Metab. 13: 903-910.
802. Li, C., Vilches-Flores, A., Zhao, M., Amiel, S. A. and others. (2012). Expression and function of monoacylglycerol lipase in mouse beta-cells and human islets of Langerhans. Cell Physiol Biochem. 30: 347-358.
803. Bermudez-Silva, F. J., Suarez, J., Baixeras, E., Cobo, N. and others. (2008). Presence of functional cannabinoid receptors in human endocrine pancreas. Diabetologia. 51: 476-487.
804. De Pasquale, A., Costa, G., and Trovato, A. (1978). The influence of cannabis on glucoregulation. Bull.Narc. 30: 3341.
805. Bermudez-Siva, F. J., Serrano, A., Diaz-Molina, F. J., Sanchez, Vera, I and others. (2006). Activation of cannabinoid CB1 receptors induces glucose intolerance in rats. Eur.J.Pharmacol. 531: 282-284.
806. Hollister, L. E. and Reaven, G. M. (1974). Delta-9-tetrahydrocannabinol and glucose tolerance. Clin.Pharmacol.Ther. 16: 297-302.
807. Rajavashisth, T. B., Shaheen, M., Norris, K. C., Pan, D. and others. (2012). Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III. BMJ Open. 2: e000494-
808. Michalski, C. W., Laukert, T., Sauliunaite, D., Pacher, P. and others. (2007). Cannabinoids ameliorate pain and reduce disease pathology in cerulein-induced acute pancreatitis. Gastroenterology. 132: 1968-1978.
809. Michalski, C. W., Maier, M., Erkan, M., Sauliunaite, D. and others. (2008). Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells. PLoS.One. 3: e1701-
810. Matsuda, K., Mikami, Y., Takeda, K., Fukuyama, S. and others. (2005). The cannabinoid 1 receptor antagonist, AM251, prolongs the survival of rats with severe acute pancreatitis. Tohoku J.Exp.Med. 207: 99-107.
811. Dembinski, A., Warzecha, Z., Ceranowicz, P., Dembinski, M. and others. (2006). Cannabinoids in acute gastric damage and pancreatitis. J.Physiol Pharmacol. 57 Suppl 5: 137-154.
812. Zyromski, N. J., Mathur, A., Pitt, H. A., Wade, T. E. and others. (2009). Cannabinoid receptor-1 blockade attenuates acute pancreatitis in obesity by an adiponectin mediated mechanism. J.Gastrointest.Surg. 13: 831-838.
813. Petrella, C., Agostini, S., Alema’, G. S., Casolini, P. and others. (2010). Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo induces dual effects on the course of acute pancreatitis. Neurogastroenterol.Motil. 22: 1248-56, e323.
814. Malfitano, A. M., Ciaglia, E., Gangemi, G., Gazzerro, P. and others. (2011). Update on the endocannabinoid system as an anticancer target. Expert.Opin.Ther.Targets. 15: 297-308.
815. Pagotto, U., Marsicano, G., Fezza, F., Theodoropoulou, M. and others. (2001). Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level. J.Clin.Endocrinol.Metab. 86: 2687-2696.
816. Schmid, P. C., Wold, L. E., Krebsbach, R. J., Berdyshev, E. V. and others. (2002). Anandamide and other Nacylethanolamines in human tumors. Lipids. 37: 907-912.
817. Nithipatikom, K., Endsley, M. P., Isbell, M. A., Falck, J. R. and others. (2004). 2-arachidonoylglycerol: a novel inhibitor of androgen-independent prostate cancer cell invasion. Cancer Res. 64: 8826-8830.
818. Petersen, G., Moesgaard, B., Schmid, P. C., Schmid, H. H. and others. (2005). Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non-tumour brain tissue. J.Neurochem. 93: 299-309.
819. Cianchi, F., Papucci, L., Schiavone, N., Lulli, M. and others. (2008). Cannabinoid receptor activation induces apoptosis through tumor necrosis factor alpha-mediated ceramide de novo synthesis in colon cancer cells. Clin.Cancer Res. 14: 7691-7700.
820. Grimaldi, C. and Capasso, A. (2011). The endocannabinoid system in the cancer therapy: an overview. Curr.Med.Chem. 18: 1575-1583.
821. Pisanti, S. and Bifulco, M. (2009). Endocannabinoid system modulation in cancer biology and therapy. Pharmacol.Res. 60: 107-116.
822. Stella, N. (2010). Cannabinoid and cannabinoid-like receptors in microglia, astrocytes, and astrocytomas. Glia. 58: 1017-1030.
823. McAllister, S. D., Chan, C., Taft, R. J., Luu, T. and others. (2005). Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. J.Neurooncol. 74: 31-40.
824. Cudaback, E., Marrs, W., Moeller, T., and Stella, N. (2010). The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas. PLoS.One. 5: e8702.-
825. Caffarel, M. M., Sarrio, D., Palacios, J., Guzman, M. and others. (2006). Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 66: 6615-6621.
826. McKallip, R. J., Nagarkatti, M., and Nagarkatti, P. S. (2005). Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J.Immunol. 174: 3281-3289.
827. Takeda, S., Yamaori, S., Motoya, E., Matsunaga, T. and others. (2008). Delta(9)-Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling. Toxicology. 245: 141-146.
828. Ligresti, A., Moriello, A. S., Starowicz, K., Matias, I. and others. (2006). Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J.Pharmacol.Exp.Ther. 318: 13751387.
829. Preet, A., Ganju, R. K., and Groopman, J. E. (2008). Delta9-Tetrahydrocannabinol inhibits epithelial growth factorinduced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene. 27: 339346.
830. Greenhough, A., Patsos, H. A., Williams, A. C., and Paraskeva, C. (2007). The cannabinoid delta(9)tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Int.J.Cancer. 121: 2172-2180.
831. Galve-Roperh, I., Sanchez, C., Cortes, M. L., Gomez, del Pulgar and others. (2000). Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat.Med. 6: 313-319.
832. Caffarel, M. M., Andradas, C., Mira, E., Perez-Gomez, E. and others. (2010). Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol.Cancer. 9: 196-206.
833. McAllister, S. D., Murase, R., Christian, R. T., Lau, D. and others. (2010). Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Res.Treat. 129: 37-47.
834. Carracedo, A., Lorente, M., Egia, A., Blazquez, C. and others. (2006). The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell. 9: 301-312.
835. Torres, S., Lorente, M., Rodriguez-Fornes, F., Hernandez-Tiedra, S. and others. (2011). A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol.Cancer Ther. 10: 90-103.
836. Guzman, M., Duarte, M. J., Blazquez, C., Ravina, J. and others. (2006). A pilot clinical study of Delta9tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br.J.Cancer. 95: 197-203.
837. Dinnes, J., Cave, C., Huang, S., and Milne, R. (2002). A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma. Br.J.Cancer. 86: 501-505.
838. Brem, H., Piantadosi, S., Burger, P. C., Walker, M. and others. (1995). Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet. 345: 1008-1012.
839. Marcu, J. P., Christian, R. T., Lau, D., Zielinski, A. J. and others. (2010). Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol.Cancer Ther. 9: 180-189.
840. Velasco, G., Carracedo, A., Blazquez, C., Lorente, M. and others. (2007). Cannabinoids and gliomas. Mol.Neurobiol. 36: 60-67.
841. Parolaro, D. and Massi, P. (2008). Cannabinoids as potential new therapy for the treatment of gliomas. Expert.Rev.Neurother. 8: 37-49.
842. Alexander, A., Smith, P. F., and Rosengren, R. J. (2009). Cannabinoids in the treatment of cancer. Cancer Lett. 285: 6-12.
843. Steffens, S., Veillard, N. R., Arnaud, C., Pelli, G. and others. (2005). Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature. 434: 782-786.
844. Sugamura, K., Sugiyama, S., Nozaki, T., Matsuzawa, Y. and others. (2009). Activated endocannabinoid system in coronary artery disease and antiinflammatory effects of cannabinoid 1 receptor blockade on macrophages. Circulation. 119: 28-36.
845. Zhao, Y., Yuan, Z., Liu, Y., Xue, J. and others. (2010). Activation of cannabinoid CB2 receptor ameliorates atherosclerosis associated with suppression of adhesion molecules. J.Cardiovasc.Pharmacol. 55: 292-298.
846. Hoyer, F. F., Steinmetz, M., Zimmer, S., Becker, A. and others. (2011). Atheroprotection via cannabinoid receptor-2 is mediated by circulating and vascular cells in vivo. J.Mol.Cell Cardiol. 51: 1007-1014.
847. Willecke, F., Zeschky, K., Ortiz, Rodriguez A., Colberg, C. and others. (2011). Cannabinoid receptor 2 signaling does not modulate atherogenesis in mice. PLoS.One. 6: e19405-
848. Netherland, C. D., Pickle, T. G., Bales, A., and Thewke, D. P. (2010). Cannabinoid receptor type 2 (CB2) deficiency alters atherosclerotic lesion formation in hyperlipidemic Ldlr-null mice. Atherosclerosis. 213: 102-108.
849. Rajesh, M., Mukhopadhyay, P., Hasko, G., Liaudet, L. and others. (2010). Cannabinoid-1 receptor activation induces reactive oxygen species-dependent and -independent mitogen-activated protein kinase activation and cell death in human coronary artery endothelial cells. Br.J.Pharmacol. 160: 688-700.
850. Singla, S., Sachdeva, R., and Mehta, J. L. (2012). Cannabinoids and atherosclerotic coronary heart disease. Clin.Cardiol. 35: 329-335.
851. Montecucco, F. and Di Marzo, V. (2012). At the heart of the matter: the endocannabinoid system in cardiovascular function and dysfunction. Trends Pharmacol.Sci. 33: 331-340.
852. Steffens, S. and Pacher, P. (2012). Targeting cannabinoid receptor CB(2) in cardiovascular disorders: promises and controversies. Br.J.Pharmacol. 167: 313-323.
853. Takeda, S., Usami, N., Yamamoto, I., and Watanabe, K. (2009). Cannabidiol-2′,6′-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor. Drug Metab Dispos. 37: 1733-1737.
854. Hezode, C., Zafrani, E. S., Roudot-Thoraval, F., Costentin, C. and others. (2008). Daily cannabis use: a novel risk factor of steatosis severity in patients with chronic hepatitis C. Gastroenterology. 134: 432-439.
855. Barrett, S. P., Darredeau, C., and Pihl, R. O. (2006). Patterns of simultaneous polysubstance use in drug using university students. Hum.Psychopharmacol. 21: 255-263.
856. Agrawal, A. and Lynskey, M. T. (2007). Does gender contribute to heterogeneity in criteria for cannabis abuse and dependence? Results from the national epidemiological survey on alcohol and related conditions. Drug Alcohol Depend. 88: 300-307.
857. Kuepper, R., van, Os J., Lieb, R., Wittchen, H. U. and others. (2011). Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ. 342: d738.-
858. Budney, A. J. and Hughes, J. R. (2006). The cannabis withdrawal syndrome. Curr.Opin.Psychiatry. 19: 233-238.
859. National Institute on Drug Abuse. NIDA InfoFacts: Marijuana. 2009.
860. Mathew, R. J., Wilson, W. H., Coleman, R. E., Turkington, T. G. and others. (1997). Marijuana intoxication and brain activation in marijuana smokers. Life Sci. 60: 2075-2089.
861. Ramaekers, J. G., Kauert, G., van, Ruitenbeek P., Theunissen, E. L. and others. (2006). High-potency marijuana impairs executive function and inhibitory motor control. Neuropsychopharmacology. 31: 2296-2303.
862. Kurzthaler, I., Hummer, M., Miller, C., Sperner-Unterweger, B. and others. (1999). Effect of cannabis use on cognitive functions and driving ability. J.Clin.Psychiatry. 60: 395-399.
863. Reisfield, G. M., Wasan, A. D., and Jamison, R. N. (2009). The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature. Pain Med. 10: 1434-1441.
864. Ashton, C. H. (1999). Adverse effects of cannabis and cannabinoids. Br.J.Anaesth. 83: 637-649.
865. de Jong, F. A., Engels, F. K., Mathijssen, R. H., van, Zuylen L. and others. (2005). Medicinal cannabis in oncology practice: still a bridge too far? J.Clin.Oncol. 23: 2886-2891.
866. Ballard, M. E. and de, Wit H. (2011). Combined effects of acute, very-low-dose ethanol and delta(9)tetrahydrocannabinol in healthy human volunteers. Pharmacol.Biochem.Behav. 97: 627-631.
867. Battista, N., Pasquariello, N., Di, Tommaso M., and Maccarrone, M. (2008). Interplay between endocannabinoids, steroids and cytokines in the control of human reproduction. J.Neuroendocrinol. 20 Suppl 1: 82-89.
868. Habayeb, O. M., Taylor, A. H., Finney, M., Evans, M. D. and others. (2008). Plasma anandamide concentration and pregnancy outcome in women with threatened miscarriage. JAMA. 299: 1135-1136.
869. Fried, P. A. (2002). Conceptual issues in behavioral teratology and their application in determining long-term sequelae of prenatal marihuana exposure. J.Child Psychol.Psychiatry. 43: 81-102.
870. Richardson, G. A., Ryan, C., Willford, J., Day, N. L. and others. (2002). Prenatal alcohol and marijuana exposure: effects on neuropsychological outcomes at 10 years. Neurotoxicol.Teratol. 24: 309-320.
871. Perez-Reyes, M. and Wall, M. E. (1982). Presence of delta9-tetrahydrocannabinol in human milk. N.Engl.J.Med. 307: 819-820.
872. Garry, A., Rigourd, V., Amirouche, A., Fauroux, V. and others. (2009). Cannabis and breastfeeding. J.Toxicol. 2009: 596149.-
873. Chait, L. D. and Perry, J. L. (1994). Acute and residual effects of alcohol and marijuana, alone and in combination, on mood and performance. Psychopharmacology (Berl). 115: 340-349.
874. Lukas, S. E. and Orozco, S. (2001). Ethanol increases plasma Delta(9)-tetrahydrocannabinol (THC) levels and subjective effects after marihuana smoking in human volunteers. Drug Alcohol Depend. 64: 143-149.
875. Li, X. Q., Andersson, T. B., Ahlstrom, M., and Weidolf, L. (2004). Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 32: 821-827.
876. Spina, E., Santoro, V., and D’Arrigo, C. (2008). Clinically relevant pharmacokinetic drug interactions with secondgeneration antidepressants: an update. Clin.Ther. 30: 1206-1227.
877. Davison, S. N. and Davison, J. S. (2011). Is there a legitimate role for the therapeutic use of cannabinoids for symptom management in chronic kidney disease? J.Pain Symptom.Manage. 41: 768-778.
878. Ellis, G. M., Jr., Mann, M. A., Judson, B. A., Schramm, N. T. and others. (1985). Excretion patterns of cannabinoid metabolites after last use in a group of chronic users. Clin.Pharmacol.Ther. 38: 572-578.
879. Lowe, R. H., Abraham, T. T., Darwin, W. D., Herning, R. and others. (2009). Extended urinary Delta9tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure. Drug Alcohol Depend. 105: 24-32.
880. Wang, T., Collet, J. P., Shapiro, S., and Ware, M. A. (2008). Adverse effects of medical cannabinoids: a systematic review. CMAJ. 178: 1669-1678.
881. Amos, A., Wiltshire, S., Bostock, Y., Haw, S. and others. (2004). ‘You can’t go without a fag…you need it for your hash’–a qualitative exploration of smoking, cannabis and young people. Addiction. 99: 77-81.
882. Hezode, C., Roudot-Thoraval, F., Nguyen, S., Grenard, P. and others. (2005). Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology. 42: 63-71.
883. Vandrey, R. G., Budney, A. J., Hughes, J. R., and Liguori, A. (2008). A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances. Drug Alcohol Depend. 92: 4854.
884. Agrawal, A., Scherrer, J. F., Lynskey, M. T., Sartor, C. E. and others. (2011). Patterns of use, sequence of onsets and correlates of tobacco and cannabis. Addict.Behav. 36: 1141-1147.
885. Wu, T. C., Tashkin, D. P., Djahed, B., and Rose, J. E. (1988). Pulmonary hazards of smoking marijuana as compared with tobacco. N.Engl.J.Med. 318: 347-351.
886. Taylor, D. R., Fergusson, D. M., Milne, B. J., Horwood, L. J. and others. (2002). A longitudinal study of the effects of tobacco and cannabis exposure on lung function in young adults. Addiction. 97: 1055-1061.
887. Tashkin, D. P. Marihuana and the lung. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
888. Taylor, D. R., Poulton, R., Moffitt, T. E., Ramankutty, P. and others. (2000). The respiratory effects of cannabis dependence in young adults. Addiction. 95: 1669-1677.
889. Denning, D. W., Follansbee, S. E., Scolaro, M., Norris, S. and others. (1991). Pulmonary aspergillosis in the acquired immunodeficiency syndrome. N.Engl.J.Med. 324: 654-662.
890. Moore, B. A., Augustson, E. M., Moser, R. P., and Budney, A. J. (2005). Respiratory effects of marijuana and tobacco use in a U.S. sample. J.Gen.Intern.Med. 20: 33-37.
891. Roth, M. D., Whittaker, K., Salehi, K., Tashkin, D. P. and others. (2004). Mechanisms for impaired effector function in alveolar macrophages from marijuana and cocaine smokers. J.Neuroimmunol. 147: 82-86.
892. LIU, D. Z., HU, C. M., HUANG, C. H., WEY, S. P. and others. (2010). Cannabidiol attenuates delayed-type hypersensitivity reactions via suppressing T-cell and macrophage reactivity. Acta Pharmacol.Sin. 31: 1611-1617.
893. Kozela, E., Pietr, M., Juknat, A., Rimmerman, N. and others. (2010). Cannabinoids Delta(9)-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-kappaB and interferonbeta/STAT proinflammatory pathways in BV-2 microglial cells. J.Biol.Chem. 285: 1616-1626.
894. Reiss, C. S. (2010). Cannabinoids and viral infections. Pharmaceuticals (Basel). 3: 1873-1886.
895. Mishkin, E. M. and Cabral, G. A. (1985). delta-9-Tetrahydrocannabinol decreases host resistance to herpes simplex virus type 2 vaginal infection in the B6C3F1 mouse. J.Gen.Virol. 66 ( Pt 12): 2539-2549.
896. Cabral, G. A., McNerney, P. J., and Mishkin, E. M. (1986). Delta-9-tetrahydrocannabinol enhances release of herpes simplex virus type 2. J.Gen.Virol. 67 ( Pt 9): 2017-2022.
897. Roth, M. D., Baldwin, G. C., and Tashkin, D. P. (2002). Effects of delta-9-tetrahydrocannabinol on human immune function and host defense. Chem.Phys.Lipids. 121: 229-239.
898. Buchweitz, J. P., Karmaus, P. W., Harkema, J. R., Williams, K. J. and others. (2007). Modulation of airway responses to influenza A/PR/8/34 by Delta9-tetrahydrocannabinol in C57BL/6 mice. J.Pharmacol.Exp.Ther. 323: 675-683.
899. Zhang, X., Wang, J. F., Kunos, G., and Groopman, J. E. (2007). Cannabinoid modulation of Kaposi’s sarcomaassociated herpesvirus infection and transformation. Cancer Res. 67: 7230-7237.
900. Herrera, R. A., Oved, J. H., and Reiss, C. S. (2008). Disruption of IFN-gamma- mediated antiviral activity in neurons: the role of cannabinoids. Viral Immunol. 21: 141-152.
901. Bredt, B. M., Higuera-Alhino, D., Shade, S. B., Hebert, S. J. and others. (2002). Short-term effects of cannabinoids on immune phenotype and function in HIV-1-infected patients. J.Clin.Pharmacol. 42: 82S-89S.
902. Chao, C., Jacobson, L. P., Tashkin, D., Martinez-Maza, O. and others. (2008). Recreational drug use and T lymphocyte subpopulations in HIV-uninfected and HIV-infected men. Drug Alcohol Depend. 94: 165-171.
903. Di Franco, M. J., Sheppard, H. W., Hunter, D. J., Tosteson, T. D. and others. (1996). The lack of association of marijuana and other recreational drugs with progression to AIDS in the San Francisco Men’s Health Study. Ann.Epidemiol. 6: 283-289.
904. Ishida, J. H., Peters, M. G., Jin, C., Louie, K. and others. (2008). Influence of cannabis use on severity of hepatitis C disease. Clin.Gastroenterol.Hepatol. 6: 69-75.
905. Bonn-Miller, M. O., Oser, M. L., Bucossi, M. M., and Trafton, J. A. (2012). Cannabis use and HIV antiretroviral therapy adherence and HIV-related symptoms (in press). J.Behav.Med.
906. Rossato, M., Pagano, C., and Vettor, R. (2008). The cannabinoid system and male reproductive functions. J.Neuroendocrinol. 20 Suppl 1: 90-93.
907. Hembree, W. C., Nahas, G. G., Zeidenberg, P., and Huang, H. F. S. Changes in human spermatozoa associated with high-dose marihuana smoking. Marihuana and medicine. Nahas, G. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa: Humana Press, 1999.
908. Hong, C. Y., Chaput de Saintonge, D. M., Turner, P., and Fairbairn, J. W. (1982). Comparison of the inhibitory action of delta-9-tetrahydrocannabinol and petroleum spirit extract of herbal cannabis on human sperm motility. Hum.Toxicol. 1: 151-154.
909. Whan, L. B., West, M. C., McClure, N., and Lewis, S. E. (2006). Effects of delta-9-tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro. Fertil.Steril. 85: 653660.
910. Lacson, J. C., Carroll, J. D., Tuazon, E., Castelao, E. J. and others. (2012). Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer. 118: 5374-5383.
911. Zuckerman, B., Frank, D. A., Hingson, R., Amaro, H. and others. (1989). Effects of maternal marijuana and cocaine use on fetal growth. N.Engl.J.Med. 320: 762-768.
912. Hurd, Y. L., Wang, X., Anderson, V., Beck, O. and others. (2005). Marijuana impairs growth in mid-gestation fetuses. Neurotoxicol.Teratol. 27: 221-229.
913. El-Marroun, H, Tiemeier, H, Steegers, E. A, Jaddoe, V. W and others. (2009). Intrauterine Cannabis Exposure Affects Fetal Growth Trajectories: The Generation R Study. J.Am.Acad.Child Adolesc.Psychiatry. 48: 1173-1181.
914. Gray, T. R., Eiden, R. D., Leonard, K. E., Connors, G. J. and others. (2010). Identifying prenatal cannabis exposure and effects of concurrent tobacco exposure on neonatal growth. Clin.Chem. 56: 1442-1450.
915. Scragg, R. K., Mitchell, E. A., Ford, R. P., Thompson, J. M. and others. (2001). Maternal cannabis use in the sudden death syndrome. Acta Paediatr. 90: 57-60.
916. Shiono, P. H., Klebanoff, M. A., Nugent, R. P., Cotch, M. F. and others. (1995). The impact of cocaine and marijuana use on low birth weight and preterm birth: a multicenter study. Am.J.Obstet.Gynecol. 172: 1927.
917. Fried, P. A., Watkinson, B., and Gray, R. (1999). Growth from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana. Neurotoxicol.Teratol. 21: 513-525.
918. van Gelder, M. M., Reefhuis, J., Caton, A. R., Werler, M. M. and others. (2010). Characteristics of pregnant illicit drug users and associations between cannabis use and perinatal outcome in a population-based study. Drug Alcohol Depend. 109: 243-247.
919. Ahmad, G. R. and Ahmad, N. (1990). Passive consumption of marijuana through milk: a low level chronic exposure to delta-9-tetrahydrocannabinol(THC). J.Toxicol.Clin.Toxicol. 28: 255-260.
920. Astley, S. J. and Little, R. E. (1990). Maternal marijuana use during lactation and infant development at one year. Neurotoxicol.Teratol. 12: 161-168.
921. Mittleman, M. A. and Mostofsky, E. (2011). Physical, psychological and chemical triggers of acute cardiovascular events: preventive strategies. Circulation. 124: 346-354.
922. Aronow, W. S. and Cassidy, J. (1974). Effect of marihuana and placebo-marihuana smoking on angina pectoris. N.Engl.J.Med. 291: 65-67.
923. Sidney, S. (2002). Cardiovascular consequences of marijuana use. J.Clin.Pharmacol. 42: 64S-70S.
924. Fisher, B. A., Ghuran, A., Vadamalai, V., and Antonios, T. F. (2005). Cardiovascular complications induced by cannabis smoking: a case report and review of the literature. Emerg.Med.J. 22: 679-680.
925. Chesher, G. and Hall, W. Effects of cannabis on the cardiovascular and gastrointestinal systems. The health effects of cannabis. Kalant, H., Corrigall, W., Hall, W., and Smart, R. Toronto: Centre of Addiction and Mental Health, 1999.
926. Merritt, J. C., Cook, C. E., and Davis, K. H. (1982). Orthostatic hypotension after delta 9-tetrahydrocannabinol marihuana inhalation. Ophthalmic Res. 14: 124-128.
927. Purnell, J. Q., Zambon, A., Knopp, R. H., Pizzuti, D. J. and others. (2000). Effect of ritonavir on lipids and postheparin lipase activities in normal subjects. AIDS. 14: 51-57.
928. Cottencin, O., Karila, L., Lambert, M., Arveiller, C. and others. (2010). Cannabis arteritis: review of the literature. J.Addict.Med. 4: 191-196.
929. Noel, B., Ruf, I., and Panizzon, R. G. (2008). Cannabis arteritis. J.Am.Acad.Dermatol. 58: S65-S67.
930. Combemale, P., Consort, T., Denis-Thelis, L., Estival, J. L. and others. (2005). Cannabis arteritis. Br.J.Dermatol. 152: 166-169.
931. Disdier, P., Granel, B., Serratrice, J., Constans, J. and others. (2001). Cannabis arteritis revisited–ten new case reports. Angiology. 52: 1-5.
932. Wolff, V., Lauer, V., Rouyer, O., Sellal, F. and others. (2011). Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction: a prospective study in 48 consecutive young patients. Stroke. 42: 1778-1780.
933. Cox, B., Chhabra, A., Adler, M., Simmons, J. and others. (2012). Cannabinoid hyperemesis syndrome: case report of a paradoxical reaction with heavy marijuana use. Case.Report.Med. 2012: 757696-
934. Batkai, S., Jarai, Z., Wagner, J. A., Goparaju, S. K. and others. (2001). Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat.Med. 7: 827-832.
935. Fernandez-Rodriguez, C. M., Romero, J., Petros, T. J., Bradshaw, H. and others. (2004). Circulating endogenous cannabinoid anandamide and portal, systemic and renal hemodynamics in cirrhosis. Liver Int. 24: 477-483.
936. Julien, B., Grenard, P., Teixeira-Clerc, F., Van Nhieu, J. T. and others. (2005). Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology. 128: 742-755.
937. Teixeira-Clerc, F., Julien, B., Grenard, P., Tran Van, Nhieu J. and others. (2006). CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat.Med. 12: 671-676.
938. Siegmund, S. V. and Schwabe, R. F. (2008). Endocannabinoids and liver disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis. Am.J.Physiol Gastrointest.Liver Physiol. 294: G357-G362.
939. Mallat, A., Hezode, C., and Lotersztajn, S. (2008). Environmental factors as disease accelerators during chronic hepatitis C. J.Hepatol. 48: 657-665.
940. Guy, G. W. and Stott, C. G. The development of Sativex®– a natural cannabis-based medicine. Cannabinoids as Therapeutics. Mechoulam, R. Basel: Birkhäuser Verlag, 2005.
941. Bolla, K. I., Brown, K., Eldreth, D., Tate, K. and others. (2002). Dose-related neurocognitive effects of marijuana use. Neurology. 59: 1337-1343.
942. Rubino, T. and Parolaro, D. (2008). Long lasting consequences of cannabis exposure in adolescence. Mol.Cell Endocrinol. 286: S108-S113.
943. Heishman, S. J., Stitzer, M. L., and Yingling, J. E. (1989). Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance. Pharmacol.Biochem.Behav. 34: 173-179.
944. Wetzel, C. D., Janowsky, D. S., and Clopton, P. L. (1982). Remote memory during marijuana intoxication. Psychopharmacology (Berl). 76: 278-281.
945. Fletcher, J. M., Page, J. B., Francis, D. J., Copeland, K. and others. (1996). Cognitive correlates of long-term cannabis use in Costa Rican men. Arch.Gen Psychiatry. 53: 1051-1057.
946. Pope, H. G., Jr., Gruber, A. J., Hudson, J. I., Cohane, G. and others. (2003). Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend. 69: 303-310.
947. Messinis, L., Kyprianidou, A., Malefaki, S., and Papathanasopoulos, P. (2006). Neuropsychological deficits in longterm frequent cannabis users. Neurology. 66: 737-739.
948. Lyketsos, C. G., Garrett, E., Liang, K. Y., and Anthony, J. C. (1999). Cannabis use and cognitive decline in persons under 65 years of age. Am.J.Epidemiol. 149: 794-800.
949. Pope, H. G., Jr., Gruber, A. J., Hudson, J. I., Huestis, M. A. and others. (2001). Neuropsychological performance in long-term cannabis users. Arch.Gen Psychiatry. 58: 909-915.
950. Pope, H. G., Jr., Gruber, A. J., and Yurgelun-Todd, D. (1995). The residual neuropsychological effects of cannabis: the current status of research. Drug Alcohol Depend. 38: 25-34.
951. Gonzalez, R., Carey, C., and Grant, I. (2002). Nonacute (residual) neuropsychological effects of cannabis use: a qualitative analysis and systematic review. J.Clin.Pharmacol. 42: 48S-57S.
952. Meier, M. H., Caspi, A., Ambler, A., Harrington, H. and others. (2012). Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc.Natl.Acad.Sci.U.S.A. 109: E2657-E2664.
953. Menetrey, A., Augsburger, M., Favrat, B., Pin, M. A. and others. (2005). Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC. J.Anal.Toxicol. 29: 327-338.
954. Asbridge, M., Poulin, C., and Donato, A. (2005). Motor vehicle collision risk and driving under the influence of cannabis: evidence from adolescents in Atlantic Canada. Accid.Anal.Prev. 37: 1025-1034.
955. Gieringer, D. H. (1988). Marijuana, driving, and accident safety. J.Psychoactive Drugs. 20: 93-101.
956. Sexton, B. F., Tunbridge, R. J., Brook-Carter, N., Jackson, P. G. and others. The influence of cannabis on driving. (2007). 477. Berkshire, UK: TRL Limited.
957. Moskowitz, H. (1985). Marihuana and driving. Accid.Anal.Prev. 17: 323-345.
958. Bosker, W. M., Kuypers, K. P., Theunissen, E. L., Surinx, A. and others. (2012). Medicinal Delta(9) tetrahydrocannabinol (dronabinol) impairs on-the-road driving performance of occasional and heavy cannabis users but is not detected in Standard Field Sobriety Tests. Addiction. 107: 1837-1844.
959. Kuypers, K. P., Legrand, S. A., Ramaekers, J. G., and Verstraete, A. G. (2012). A case-control study estimating accident risk for alcohol, medicines and illegal drugs. PLoS.One. 7: e43496-
960. Laumon, B., Gadegbeku, B., Martin, J. L., and Biecheler, M. B. (2005). Cannabis intoxication and fatal road crashes in France: population based case-control study. BMJ. 331: 1371-
961. Khiabani, H. Z., Bramness, J. G., Bjorneboe, A., and Morland, J. (2006). Relationship between THC concentration in blood and impairment in apprehended drivers. Traffic.Inj.Prev. 7: 111-116.
962. Thornicroft, G. (1990). Cannabis and psychosis. Is there epidemiological evidence for an association? Br.J.Psychiatry. 157: 25-33.
963. Morrison, P. D., Zois, V., McKeown, D. A., Lee, T. D. and others. (2009). The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol.Med. 39: 1607-1616.
964. Kotin, J., Post, R. M., and Goodwin, F. K. (1973). 9 -Tetrahydrocannabinol in depressed patients. Arch.Gen.Psychiatry. 28: 345-348.
965. Ablon, S. L. and Goodwin, F. K. (1974). High frequency of dysphoric reactions to tetrahydrocannabinol among depressed patients. Am.J.Psychiatry. 131: 448-453.
966. Glass, R. M., Uhlenhuth, E. H., Hartel, F. W., Schuster, C. R. and others. (1980). A single dose study of nabilone, a synthetic cannabinoid. Psychopharmacology (Berl). 71: 137-142.
967. Glass, R. M., Uhlenhuth, E. H., Hartel, F. W., Schuster, C. R. and others. (1981). Single-dose study of nabilone in anxious volunteers. J.Clin.Pharmacol. 21: 383S-396S.
968. Degenhardt, L., Hall, W., and Lynskey, M. (2003). Exploring the association between cannabis use and depression. Addiction. 98: 1493-1504.
969. Harder, V. S., Morral, A. R., and Arkes, J. (2006). Marijuana use and depression among adults: Testing for causal associations. Addiction. 101: 1463-1472.
970. Harder, V. S., Stuart, E. A., and Anthony, J. C. (2008). Adolescent cannabis problems and young adult depression: male-female stratified propensity score analyses. Am.J.Epidemiol. 168: 592-601.
971. Stinson, F. S., Ruan, W. J., Pickering, R., and Grant, B. F. (2006). Cannabis use disorders in the USA: prevalence, correlates and co-morbidity. Psychol.Med. 36: 1447-1460.
972. van Laar, M., van Dorsselaer, S., Monshouwer, K., and de Graaf, R. (2007). Does cannabis use predict the first incidence of mood and anxiety disorders in the adult population? Addiction. 102: 1251-1260.
973. Chabrol, H., Chauchard, E., and Girabet, J. (2008). Cannabis use and suicidal behaviours in high-school students. Addict.Behav. 33: 152-155.
974. Pedersen, W. (2008). Does cannabis use lead to depression and suicidal behaviours? A population-based longitudinal study. Acta Psychiatr.Scand. 118: 395-403.
975. Henquet, C., Krabbendam, L., de, Graaf R., ten, Have M. and others. (2006). Cannabis use and expression of mania in the general population. J.Affect.Disord. 95: 103-110.
976. Strakowski, S. M., DelBello, M. P., Fleck, D. E., Adler, C. M. and others. (2007). Effects of co-occurring cannabis use disorders on the course of bipolar disorder after a first hospitalization for mania. Arch.Gen.Psychiatry. 64: 57-64.
977. Agrawal, A., Nurnberger, J. I., Jr., and Lynskey, M. T. (2011). Cannabis involvement in individuals with bipolar disorder. Psychiatry Res. 185: 459-461.
978. De Pradier, M., Gorwood, P., Beaufils, B., Ades, J. and others. (2010). Influence of the serotonin transporter gene polymorphism, cannabis and childhood sexual abuse on phenotype of bipolar disorder: a preliminary study. Eur.Psychiatry. 25: 323-327.
979. Baethge, C., Hennen, J., Khalsa, H. M., Salvatore, P. and others. (2008). Sequencing of substance use and affective morbidity in 166 first-episode bipolar I disorder patients. Bipolar.Disord. 10: 738-741.
980. Martinez-Gras, I., Hoenicka, J., Ponce, G., Rodriguez-Jimenez, R. and others. (2006). (AAT)n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population. Eur.Arch.Psychiatry Clin.Neurosci. 256: 437-441.
981. Monteleone, P., Bifulco, M., Maina, G., Tortorella, A. and others. (2010). Investigation of CNR1 and FAAH endocannabinoid gene polymorphisms in bipolar disorder and major depression. Pharmacol.Res. 61: 400404.
982. Lagerberg, T. V., Sundet, K., Aminoff, S. R., Berg, A. O. and others. (2011). Excessive cannabis use is associated with earlier age at onset in bipolar disorder. Eur.Arch.Psychiatry Clin.Neurosci. 261: 397-405.
983. Braga, R. J., Burdick, K. E., Derosse, P., and Malhotra, A. K. (2012). Cognitive and clinical outcomes associated with cannabis use in patients with bipolar I disorder. Psychiatry Res. 200: 242-245.
984. Allebeck, P. Cannabis and psychiatric syndrome. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
985. Caspari, D. (1999). Cannabis and schizophrenia: results of a follow-up study. Eur.Arch.Psychiatry Clin.Neurosci. 249: 45-49.
986. Zammit, S., Allebeck, P., Andreasson, S., Lundberg, I. and others. (2002). Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ. 325: 1199-1203.
987. Arseneault, L., Cannon, M., Poulton, R., Murray, R. and others. (2002). Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ. 325: 1212-1213.
988. Arseneault, L., Cannon, M., Witton, J., and Murray, R. M. (2004). Causal association between cannabis and psychosis: examination of the evidence. Br.J.Psychiatry. 184: 110-117.
989. Decoster, J., van, Os J., Kenis, G., Henquet, C. and others. (2011). Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction. Am.J.Med.Genet.B Neuropsychiatr.Genet. 156B: 363-369.
990. Tunbridge, E. M., Harrison, P. J., and Weinberger, D. R. (2006). Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biol.Psychiatry. 60: 141-151.
991. McIntosh, A. M., Baig, B. J., Hall, J., Job, D. and others. (2007). Relationship of catechol-O-methyltransferase variants to brain structure and function in a population at high risk of psychosis. Biol.Psychiatry. 61: 11271134.
992. Miyake, N., Thompson, J., Skinbjerg, M., and Abi-Dargham, A. (2011). Presynaptic dopamine in schizophrenia. CNS.Neurosci.Ther. 17: 104-109.
993. Fan, J. B., Zhang, C. S., Gu, N. F., Li, X. W. and others. (2005). Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biol.Psychiatry. 57: 139-144.
994. Ayalew, M., Le-Niculescu, H., Levey, D. F., Jain, N. and others. (2012). Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction. Mol.Psychiatry. 17: 887-905.
995. D’Souza, D. C., Sewell, R. A., and Ranganathan, M. (2009). Cannabis and psychosis/schizophrenia: human studies. Eur.Arch.Psychiatry Clin.Neurosci. 259: 413-431.
996. Castle, D. J. and Solowij, N. Acute and subacute psychomimetic effects of cannabis in humans. Marijuana and madness. Castle, D. and Murray, R. Cambridge: Cambridge University Press, 2004.
997. Fridberg, D. J., Vollmer, J. M., O’Donnell, B. F., and Skosnik, P. D. (2011). Cannabis users differ from non-users on measures of personality and schizotypy. Psychiatry Res. 186: 46-52.
998. Thompson, G. R., Rosenkrantz, H., Schaeppi, U. H., and Braude, M. C. (1973). Comparison of acute oral toxicity of cannabinoids in rats, dogs and monkeys. Toxicol.Appl.Pharmacol. 25: 363-372.
999. Robson, P. (2001). Therapeutic aspects of cannabis and cannabinoids. Br.J.Psychiatry. 178: 107-115.
1000. Weinstein, A. M. and Gorelick, D. A. (2011). Pharmacological treatment of cannabis dependence. Curr.Pharm.Des. 17: 1351-1358.
1. Rodriguez de Fonseca, F., del Arco, I, Bermudez-Silva, F. J., Bilbao, A. and others. (2005). The endocannabinoid system: physiology and pharmacology. Alcohol Alcohol. 40: 2-14.
2. Serrano, A. and Parsons, L. H. (2011). Endocannabinoid influence in drug reinforcement, dependence and addictionrelated behaviors. Pharmacol.Ther. 132: 215-241.
3. Maccarrone, M., Gasperi, V., Catani, M. V., Diep, T. A. and others. (2010). The endocannabinoid system and its relevance for nutrition. Annu.Rev.Nutr. 30: 423-440.
4. Aggarwal, S. K. (2012). Cannabinergic Pain Medicine: A Concise Clinical Primer and Survey of Randomizedcontrolled Trial Results. Clin.J.Pain. 29: 162-171.
5. Bradshaw, H. B. and Walker, J. M. (2005). The expanding field of cannabimimetic and related lipid mediators. Br.J.Pharmacol. 144: 459-465.
6. De Petrocellis, L. and Di Marzo, V. (2009). An introduction to the endocannabinoid system: from the early to the latest concepts. Best.Pract.Res.Clin.Endocrinol.Metab. 23: 1-15.
7. De Petrocellis, L. and Di, Marzo, V. (2010). Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: focus on G-protein-coupled receptors and transient receptor potential channels. J.Neuroimmune.Pharmacol. 5: 103-121.
8. O’Sullivan, S. E. and Kendall, D. A. (2010). Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology. 215: 611-616.
9. Hansen, H. S. (2010). Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain. Exp.Neurol. 224: 48-55.
10. Ben-Shabat, S., Fride, E., Sheskin, T., Tamiri, T. and others. (1998). An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur.J.Pharmacol. 353: 23-31.
11. Quarta, C., Mazza, R., Obici, S., Pasquali, R. and others. (2011). Energy balance regulation by endocannabinoids at central and peripheral levels. Trends Mol.Med. 17: 518-526.
12. Battista, N., Di, Tommaso M., Bari, M., and Maccarrone, M. (2012). The endocannabinoid system: an overview. Front.Behav.Neurosci. 6: 9-
13. Horvath, B., Mukhopadhyay, P., Hasko, G., and Pacher, P. (2012). The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications. Am.J.Pathol. 180: 432-442.
14. Hermanson, D. J. and Marnett, L. J. (2011). Cannabinoids, endocannabinoids, and cancer. Cancer Metastasis Rev. 30: 599-612.
15. Rouzer, C. A. and Marnett, L. J. (2011). Endocannabinoid oxygenation by cyclooxygenases, lipoxygenases, and cytochromes P450: cross-talk between the eicosanoid and endocannabinoid signaling pathways. Chem.Rev. 111: 5899-5921.
16. Pertwee, R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br.J.Pharmacol. 153: 199-215.
17. Di Marzo, V., Piscitelli, F., and Mechoulam, R. (2011). Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. Handb.Exp.Pharmacol. 75-104.
18. Bab, I. and Zimmer, A. (2008). Cannabinoid receptors and the regulation of bone mass. Br.J.Pharmacol. 153: 182188.
19. Howlett, A. C., Barth, F., Bonner, T. I., Cabral, G. and others. (2002). International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol.Rev. 54: 161-202.
20. Pertwee, R. G., Howlett, A. C., Abood, M. E., Alexander, S. P. and others. (2010). International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB and CB. Pharmacol.Rev. 62: 588-631.
21. Kraft, B. (2012). Is there any clinically relevant cannabinoid-induced analgesia? Pharmacology. 89: 237-246.
22. Guindon, J. and Hohmann, A. G. (2009). The endocannabinoid system and pain. CNS.Neurol.Disord Drug Targets. 8: 403-421.
23. Teixeira, D., Pestana, D., Faria, A., Calhau, C. and others. (2010). Modulation of adipocyte biology by delta(9)tetrahydrocannabinol. Obesity.(Silver.Spring). 18: 2077-2085.
24. Greineisen, W. E. and Turner, H. (2010). Immunoactive effects of cannabinoids: considerations for the therapeutic use of cannabinoid receptor agonists and antagonists. Int.Immunopharmacol. 10: 547-555.
25. Jean-Gilles, L., Gran, B., and Constantinescu, C. S. (2010). Interaction between cytokines, cannabinoids and the nervous system. Immunobiology. 215: 606-610.
26. Rice, W., Shannon, J. M., Burton, F., and Fiedeldey, D. (1997). Expression of a brain-type cannabinoid receptor (CB1) in alveolar Type II cells in the lung: regulation by hydrocortisone. Eur.J.Pharmacol. 327: 227-232.
27. Shmist, Y. A., Goncharov, I., Eichler, M., Shneyvays, V. and others. (2006). Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production. Mol.Cell Biochem. 283: 75-83.
28. Wright, K., Rooney, N., Feeney, M., Tate, J. and others. (2005). Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology. 129: 437-453.
29. Marquez, L., Suarez, J., Iglesias, M., Bermudez-Silva, F. J. and others. (2009). Ulcerative colitis induces changes on the expression of the endocannabinoid system in the human colonic tissue. PLoS.One. 4: e6893.-
30. Linari, G., Agostini, S., Amadoro, G., Ciotti, M. T. and others. (2009). Involvement of cannabinoid CB1- and CB2receptors in the modulation of exocrine pancreatic secretion. Pharmacol.Res. 59: 207-214.
31. Izzo, A. A. and Sharkey, K. A. (2010). Cannabinoids and the gut: new developments and emerging concepts. Pharmacol.Ther. 126: 21-38.
32. Purohit, V., Rapaka, R., and Shurtleff, D. (2010). Role of cannabinoids in the development of fatty liver (steatosis). AAPS.J. 12: 233-237.
33. Mallat, A., Teixeira-Clerc, F., Deveaux, V., Manin, S. and others. (2011). The endocannabinoid system as a key mediator during liver diseases: new insights and therapeutic openings. Br.J.Pharmacol. 163: 1432-1440.
34. Jenkin, K. A., McAinch, A. J., Grinfeld, E., and Hryciw, D. H. (2010). Role for cannabinoid receptors in human proximal tubular hypertrophy. Cell Physiol Biochem. 26: 879-886.
35. Gratzke, C., Streng, T., Park, A., Christ, G. and others. (2009). Distribution and function of cannabinoid receptors 1 and 2 in the rat, monkey and human bladder. J.Urol. 181: 1939-1948.
36. Tyagi, P., Tyagi, V., Yoshimura, N., and Chancellor, M. (2010). Functional role of cannabinoid receptors in urinary bladder. Indian J.Urol. 26: 26-35.
37. Karasu, T., Marczylo, T. H., Maccarrone, M., and Konje, J. C. (2011). The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility. Hum.Reprod.Update. 17: 347-361.
38. Idris, A. I. and Ralston, S. H. (2010). Cannabinoids and bone: friend or foe? Calcif.Tissue Int. 87: 285-297.
39. Watkins, B. A., Hutchins, H., Li, Y., and Seifert, M. F. (2010). The endocannabinoid signaling system: a marriage of PUFA and musculoskeletal health. J.Nutr.Biochem. 21: 1141-1152.
40. Richardson, D., Pearson, R. G., Kurian, N., Latif, M. L. and others. (2008). Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res.Ther. 10: R43.-
41. Biro, T., Toth, B. I., Hasko, G., Paus, R. and others. (2009). The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol.Sci. 30: 411-420.
42. Mackie, K. (2008). Signaling via CNS cannabinoid receptors. Mol.Cell Endocrinol. 286: S60-S65.
43. Cabral, G. A. Marihuana and the immune system. Marihuana and medicine. Nahas, G. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa: Humana Press, 1999.
44. De Petrocellis, L., Ligresti, A., Moriello, A. S., Allara, M. and others. (2011). Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br.J.Pharmacol. 163: 1479-1494.
45. Alger, B. E. (2004). Endocannabinoids: getting the message across. Proc.Natl.Acad.Sci.U.S.A. 101: 8512-8513.
46. Bisogno, T. (2008). Endogenous cannabinoids: structure and metabolism. J.Neuroendocrinol. 20 Suppl 1: 1-9.
47. Miller, L. K. and Devi, L. A. (2011). The highs and lows of cannabinoid receptor expression in disease: mechanisms and their therapeutic implications. Pharmacol.Rev. 63: 461-470.
48. Martin-Sanchez, E., Furukawa, T. A., Taylor, J., and Martin, J. L. (2009). Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 10: 1353-1368.
49. Gowran, A., Noonan, J., and Campbell, V. A. (2011). The multiplicity of action of cannabinoids: implications for treating neurodegeneration. CNS.Neurosci.Ther. 17: 637-644.
50. Guindon, J., Lai, Y., Takacs, S. M., Bradshaw, H. B. and others. (2012). Alterations in endocannabinoid tone following chemotherapy-induced peripheral neuropathy: Effects of endocannabinoid deactivation inhibitors targeting fatty-acid amide hydrolase and monoacylglycerol lipase in comparison to reference analgesics following cisplatin treatment. Pharmacol.Res. 67: 94-109.
51. Russo, E. B. and Hohmann, A. G. Role of cannabinoids in pain management. Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Behavioral Approaches: The AMERICAN ACADEMY OF PAIN MEDICINE Textbook on Patient Management . Deer, T. R. and Leong, M. S. New York: Springer, 2012.
52. Guzman, M. (2003). Cannabinoids: potential anticancer agents. Nat.Rev.Cancer. 3: 745-755.
53. Di Marzo, V, Bifulco, M., and De Petrocellis, L. (2004). The endocannabinoid system and its therapeutic exploitation. Nat.Rev.Drug Discov. 3: 771-784.
54. Bazzaz, F. A., Dusek, D., Seigler, D. S., and Haney, A. W. (1975). Photosynthesis and cannabinoid content of temperate and tropical populations of Cannabis sativa. Biochemical Systematics and Ecology. 3: 15-18.
55. Elsohly, M. A. and Slade, D. (2005). Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci. 78: 539-548.
56. Zhu, H. J., Wang, J. S., Markowitz, J. S., Donovan, J. L. and others. (2006). Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J.Pharmacol.Exp.Ther. 317: 850-857.
57. Balducci, C., Nervegna, G., and Cecinato, A. (2009). Evaluation of principal cannabinoids in airborne particulates. Anal.Chim.Acta. 641: 89-94.
58. Yamaori, S., Kushihara, M., Yamamoto, I., and Watanabe, K. (2010). Characterization of major phytocannabinoids, cannabidiol and cannabinol, as isoform-selective and potent inhibitors of human CYP1 enzymes. Biochem.Pharmacol. 79: 1691-1698.
59. Hillig, K. W. and Mahlberg, P. G. (2004). A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae). Am.J.Bot. 91: 966-975.
60. Mehmedic, Z., Chandra, S., Slade, D., Denham, H. and others. (2010). Potency Trends of Delta(9)-THC and Other Cannabinoids in Confiscated Cannabis Preparations from 1993 to 2008*. J.Forensic Sci. 55: 1209-1217.
61. Whittle, B. A. and Guy, G. W. Development of cannabis-based medicines: risk, benefit and serendipity. The Medicinal Uses of Cannabis and Cannabinoids. Guy, G. W., Whittle, B. A., and Robson, P. J. London: Pharmaceutical Press, 2004.
62. Huestis, M. A. (2007). Human cannabinoid pharmacokinetics. Chem.Biodivers. 4: 1770-1804.
63. Dussy, F. E., Hamberg, C., Luginbuhl, M., Schwerzmann, T. and others. (2005). Isolation of Delta9-THCA-A from hemp and analytical aspects concerning the determination of Delta9-THC in cannabis products. Forensic Sci.Int. 149: 3-10.
64. Ashton, C. H. (2001). Pharmacology and effects of cannabis: a brief review. Br.J.Psychiatry. 178: 101-106.
65. Health Canada. Product Information Sheet on Dried Marihuana (Cannabis). 2008.
66. Health Canada. Product information sheet on dried marihuana (Cannabis spp.). Health Canada website. Health Canada. 2005.
67. Fischedick, J., Van der Kooy, F., and Verpoorte, R. (2010). Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor. Chem.Pharm.Bull.(Tokyo). 58: 201-207.
68. Maertens, R. M., White, P. A., Rickert, W., Levasseur, G. and others. (2009). The genotoxicity of mainstream and sidestream marijuana and tobacco smoke condensates. Chem.Res.Toxicol. 22: 1406-1414.
69. International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans: Tobacco smoke and involuntary smoking. 2004.
70. Moir, D., Rickert, W. S., Levasseur, G., Larose, Y. and others. (2008). A comparison of mainstream and sidestream marijuana and tobacco cigarette smoke produced under two smoking conditions. Chem.Res.Toxicol. 21: 494-502.
71. Russo, E. B. and McPartland, J. M. (2003). Cannabis is more than simply delta(9)-tetrahydrocannabinol. Psychopharmacology (Berl). 165: 431-432.
72. Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br.J.Pharmacol. 163: 1344-1364.
73. Baker, P. B., Taylor, B. J., and Gough, T. A. (1981). The tetrahydrocannabinol and tetrahydrocannabinolic acid content of cannabis products. J.Pharm.Pharmacol. 33: 369-372.
74. Garrett, E. R. and Hunt, C. A. (1974). Physiochemical properties, solubility, and protein binding of delta9tetrahydrocannabinol. J.Pharm.Sci. 63: 1056-1064.
75. Fairbairn, J. W., Liebmann, J. A., and Rowan, M. G. (1976). The stability of Cannabis and its preparations on storage. J.Pharm.Pharmacol. 28: 1-7.
76. Thomas, B. F., Parker, V. L., Caddell, L. W., Jones, L. V. and others. Composition and stability of a standard marihuana cigarette. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
77. Govaerts, S. J., Hermans, E., and Lambert, D. M. (2004). Comparison of cannabinoid ligands affinities and efficacies in murine tissues and in transfected cells expressing human recombinant cannabinoid receptors. Eur.J.Pharm.Sci. 23: 233-243.
78. Pertwee, R. G. (2010). Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists. Curr.Med.Chem. 17: 1360-1381.
79. Hajos, N., Ledent, C., and Freund, T. F. (2001). Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience. 106: 1-4.
80. Darmani, N. A., Janoyan, J. J., Crim, J., and Ramirez, J. (2007). Receptor mechanism and antiemetic activity of structurally-diverse cannabinoids against radiation-induced emesis in the least shrew. Eur.J.Pharmacol. 563: 187-196.
81. Abrahamov, A., Abrahamov, A., and Mechoulam, R. (1995). An efficient new cannabinoid antiemetic in pediatric oncology. Life Sci. 56: 2097-2102.
82. Izzo, A. A., Borrelli, F., Capasso, R., Di, Marzo, V and others. (2009). Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol.Sci. 30: 515-527.
83. Institute of Medicine. Cannabinoids and animal physiology. Marijuana and medicine: Assessing the science base. Joy, J. E., Watson, S. J., and Benson, J. A. Washington, DC: National Academy Press, 1999.
84. Musty, R. E. Natural cannabinoids: interactions and effects. The medicinal uses of cannabis and cannabinoids. Guy, G. W, Whittle, B. A., and Robson, P. J. London: Pharmaceutical Press, 2004.
85. Ruhaak, L. R., Felth, J., Karlsson, P. C., Rafter, J. J. and others. (2011). Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol.Pharm.Bull. 34: 774-778.
86. Cascio, M. G., Gauson, L. A., Stevenson, L. A., Ross, R. A. and others. (2010). Evidence that the plant cannabinoid cannabigerol is a highly potent alpha2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br.J.Pharmacol. 159: 129-141.
87. Brown, A. J. (2007). Novel cannabinoid receptors. Br.J.Pharmacol. 152: 567-575.
88. Parker, L. A., Rock, E., and Limebeer, C. (2010). Regulation of nausea and vomiting by cannabinoids. Br.J.Pharmacol. 163: 1411-1422.
89. Thomas, A., Stevenson, L. A., Wease, K. N., Price, M. R. and others. (2005). Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist. Br.J.Pharmacol. 146: 917-926.
90. Bolognini, D., Costa, B., Maione, S., Comelli, F. and others. (2010). The plant cannabinoid Delta9tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. Br.J.Pharmacol. 160: 677-687.
91. Hill, A. J., Weston, S. E., Jones, N. A., Smith, I. and others. (2010). Delta-Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. Epilepsia. 51: 1522-1532.
92. Riedel, G., Fadda, P., McKillop-Smith, S., Pertwee, R. G. and others. (2009). Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. Br.J.Pharmacol. 156: 1154-1166.
93. Pertwee, R. G. (2005). Pharmacological actions of cannabinoids. Handb.Exp.Pharmacol. 1-51.
94. Jones, G. and Pertwee, R. G. (1972). A metabolic interaction in vivo between cannabidiol and 1 tetrahydrocannabinol. Br.J.Pharmacol. 45: 375-377.
95. Karniol, I. G., Shirakawa, I., Kasinski, N., Pfeferman, A. and others. (1974). Cannabidiol interferes with the effects of delta 9 – tetrahydrocannabinol in man. Eur.J.Pharmacol. 28: 172-177.
96. Zuardi, A. W., Finkelfarb, E., Bueno, O. F., Musty, R. E. and others. (1981). Characteristics of the stimulus produced by the mixture of cannabidiol with delta 9-tetrahydrocannabinol. Arch.Int.Pharmacodyn.Ther. 249: 137146.
97. Zuardi, A. W., Shirakawa, I., Finkelfarb, E., and Karniol, I. G. (1982). Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 76: 245-250.
98. Zuardi, A. W. and Karniol, I. G. (1983). Effects on variable-interval performance in rats of delta 9tetrahydrocannabinol and cannabidiol, separately and in combination. Braz.J.Med.Biol.Res. 16: 141-146.
99. Reid, M. J. and Bornheim, L. M. (2001). Cannabinoid-induced alterations in brain disposition of drugs of abuse. Biochem.Pharmacol. 61: 1357-1367.
100. Fadda, P., Robinson, L., Fratta, W., Pertwee, R. G. and others. (2004). Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats. Neuropharmacology. 47: 1170-1179.
101. Ilan, A. B., Gevins, A., Coleman, M., Elsohly, M. A. and others. (2005). Neurophysiological and subjective profile of marijuana with varying concentrations of cannabinoids. Behav.Pharmacol. 16: 487-496.
102. Nadulski, T., Pragst, F., Weinberg, G., Roser, P. and others. (2005). Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC versus standardized cannabis extract. Ther.Drug Monit. 27: 799-810.
103. Varvel, S. A., Wiley, J. L., Yang, R., Bridgen, D. T. and others. (2006). Interactions between THC and cannabidiol in mouse models of cannabinoid activity. Psychopharmacology (Berl). 186: 226-234.
104. Fusar-Poli, P., Crippa, J. A., Bhattacharyya, S., Borgwardt, S. J. and others. (2009). Distinct effects of {delta}9tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch.Gen.Psychiatry. 66: 95-105.
105. Bhattacharyya, S., Morrison, P. D., Fusar-Poli, P., Martin-Santos, R. and others. (2010). Opposite effects of delta-9tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 35: 764-774.
106. Winton-Brown, T. T., Allen, P., Bhattacharyya, S., Borgwardt, S. J. and others. (2011). Modulation of auditory and visual processing by delta-9-tetrahydrocannabinol and cannabidiol: an FMRI study. Neuropsychopharmacology. 36: 1340-1348.
107. Karschner, E. L., Darwin, W. D., McMahon, R. P., Liu, F. and others. (2011). Subjective and physiological effects after controlled Sativex and oral THC administration. Clin.Pharmacol.Ther. 89: 400-407.
108. Karschner, E. L., Darwin, W. D., Goodwin, R. S., Wright, S. and others. (2011). Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin.Chem. 57: 66-75.
109. Zuardi, A. W., Hallak, J. E., and Crippa, J. A. (2012). Interaction between cannabidiol (CBD) and (9)tetrahydrocannabinol (THC): influence of administration interval and dose ratio between the cannabinoids. Psychopharmacology (Berl). 219: 247-249.
110. Klein, C., Karanges, E., Spiro, A., Wong, A. and others. (2011). Cannabidiol potentiates Delta(9)tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. Psychopharmacology (Berl). 218: 443-457.
111. Wachtel, S. R., Elsohly, M. A., Ross, S. A., Ambre, J. and others. (2002). Comparison of the subjective effects of Delta(9)-tetrahydrocannabinol and marijuana in humans. Psychopharmacology (Berl). 161: 331-339.
112. Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D. and others. (2010). Multicenter, doubleblind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J.Pain Symptom.Manage. 39: 167-179.
113. Schubart, C. D., Sommer, I. E., van Gastel, W. A., Goetgebuer, R. L. and others. (2011). Cannabis with high cannabidiol content is associated with fewer psychotic experiences. Schizophr.Res. 130: 216-221.
114. Kumar, R. N., Chambers, W. A., and Pertwee, R. G. (2001). Pharmacological actions and therapeutic uses of cannabis and cannabinoids. Anaesthesia. 56: 1059-1068.
115. British Medical Association. Therapeutic uses of cannabis. Amsterdam: Harwood Academic Publishers, 1997.
116. Hill, M. N., Froese, L. M., Morrish, A. C., Sun, J. C. and others. (2006). Alterations in behavioral flexibility by cannabinoid CB1 receptor agonists and antagonists. Psychopharmacology (Berl). 187: 245-259.
117. Zuurman, L., Ippel, A. E., Moin, E., and van Gerven, J. M. (2009). Biomarkers for the effects of cannabis and THC in healthy volunteers. Br.J.Clin.Pharmacol. 67: 5-21.
118. Institute of Medicine. First, do no harm: consequences of marijuana use and abuse. Marijuana and medicine: Assessing the science base. Joy, J. E., Watson, S. J., and Benson, J. A. Washington, DC: National Academy Press, 1999.
119. Beaconsfield, P., Ginsburg, J., and Rainsbury, R. (1972). Marihuana smoking. Cardiovascular effects in man and possible mechanisms. N.Engl.J.Med. 287: 209-212.
120. Perez-Reyes, M. (1990). Marijuana smoking: factors that influence the bioavailability of tetrahydrocannabinol. NIDA Res.Monogr. 99: 42-62.
121. Aryana, A. and Williams, M. A. (2007). Marijuana as a trigger of cardiovascular events: speculation or scientific certainty? Int.J.Cardiol. 118: 141-144.
122. Hall, W. and Solowij, N. (1998). Adverse effects of cannabis. Lancet. 352: 1611-1616.
123. Ameri, A. (1999). The effects of cannabinoids on the brain. Prog.Neurobiol. 58: 315-348.
124. Barnett, G., Licko, V., and Thompson, T. (1985). Behavioral pharmacokinetics of marijuana. Psychopharmacology (Berl). 85: 51-56.
125. Kelly, T. H., Foltin, R. W., and Fischman, M. W. (1993). Effects of smoked marijuana on heart rate, drug ratings and task performance by humans. Behav.Pharmacol. 4: 167-178.
126. Fant, R. V., Heishman, S. J., Bunker, E. B., and Pickworth, W. B. (1998). Acute and residual effects of marijuana in humans. Pharmacol.Biochem.Behav. 60: 777-784.
127. Hollister, L. E. (1998). Health aspects of cannabis: revisited. Int.J.Neuropsychopharmacol. 1: 71-80.
128. Miller, L. L. Marihuana: Acute effects on human memory. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
129. Hart, C. L., Ilan, A. B., Gevins, A., Gunderson, E. W. and others. (2010). Neurophysiological and cognitive effects of smoked marijuana in frequent users. Pharmacol.Biochem.Behav. 96: 333-341.
130. Crean, R. D., Crane, N. A., and Mason, B. J. (2011). An Evidence Based Review of Acute and Long-Term Effects of Cannabis Use on Executive Cognitive Functions. J.Addict.Med. 5: 1-8.
131. Heishman, S. J., Huestis, M. A., Henningfield, J. E., and Cone, E. J. (1990). Acute and residual effects of marijuana: profiles of plasma THC levels, physiological, subjective, and performance measures. Pharmacol.Biochem.Behav. 37: 561-565.
132. Curran, H. V., Brignell, C., Fletcher, S., Middleton, P. and others. (2002). Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users. Psychopharmacology (Berl). 164: 61-70.
133. Ramaekers, J. G., Moeller, M. R., van, Ruitenbeek P., Theunissen, E. L. and others. (2006). Cognition and motor control as a function of Delta9-THC concentration in serum and oral fluid: limits of impairment. Drug Alcohol Depend. 85: 114-122.
134. O’Kane, C. J., Tutt, D. C., and Bauer, L. A. (2002). Cannabis and driving: a new perspective. Emerg.Med.(Fremantle.). 14: 296-303.
135. Hansteen, R. W., Miller, R. D., Lonero, L., Reid, L. D. and others. (1976). Effects of cannabis and alcohol on automobile driving and psychomotor tracking. Ann.N.Y.Acad.Sci. 282: 240-256.
136. Leirer, V. O., Yesavage, J. A., and Morrow, D. G. (1991). Marijuana carry-over effects on aircraft pilot performance. Aviat.Space Environ.Med. 62: 221-227.
137. Smiley, A. Marijuana: On-road and driving-simulator studies. The Health Effects of Cannabis. Kalant, H., Corrigall, W., Hall, W., and Smart, R. Toronto, Canada: Centre of Addiction and Mental Health, 1999.
138. van Os, J., Bak, M., Hanssen, M., Bijl, R. V. and others. (2002). Cannabis use and psychosis: a longitudinal population-based study. Am.J.Epidemiol. 156: 319-327.
139. D’Souza, D. C., Abi-Saab, W. M., Madonick, S., Forselius-Bielen, K. and others. (2005). Delta-9tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biol.Psychiatry. 57: 594-608.
140. D’Souza, D. C., Perry, E., MacDougall, L., Ammerman, Y. and others. (2004). The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology. 29: 1558-1572.
141. Moore, T. H., Zammit, S., Lingford-Hughes, A., Barnes, T. R. and others. (2007). Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 370: 319-328.
142. Abrams, D. I., Jay, C. A., Shade, S. B., Vizoso, H. and others. (2007). Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 68: 515-521.
143. Henquet, C., van, Os J., Kuepper, R., Delespaul, P. and others. (2010). Psychosis reactivity to cannabis use in daily life: an experience sampling study. Br.J.Psychiatry. 196: 447-453.
144. Korver, N., Nieman, D. H., Becker, H. E., van de Fliert, J. R. and others. (2010). Symptomatology and neuropsychological functioning in cannabis using subjects at ultra-high risk for developing psychosis and healthy controls. Aust.N.Z.J.Psychiatry. 44: 230-236.
145. Favrat, B., Menetrey, A., Augsburger, M., Rothuizen, L. E. and others. (2005). Two cases of “cannabis acute psychosis” following the administration of oral cannabis. BMC.Psychiatry. 5: 17-22.
146. Henquet, C., Krabbendam, L., Spauwen, J., Kaplan, C. and others. (2005). Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ. 330: 11-15.
147. Crippa, J. A., Zuardi, A. W., Martin-Santos, R., Bhattacharyya, S. and others. (2009). Cannabis and anxiety: a critical review of the evidence. Hum.Psychopharmacol. 24: 515-523.
148. van Rossum, I, Boomsma, M., Tenback, D., Reed, C. and others. (2009). Does cannabis use affect treatment outcome in bipolar disorder? A longitudinal analysis. J.Nerv.Ment.Dis. 197: 35-40.
149. Ongur, D., Lin, L., and Cohen, B. M. (2009). Clinical characteristics influencing age at onset in psychotic disorders. Compr.Psychiatry. 50: 13-19.
150. De Hert, M., Wampers, M., Jendricko, T., Franic, T. and others. (2011). Effects of cannabis use on age at onset in schizophrenia and bipolar disorder. Schizophr.Res. 126: 270-276.
151. Harder, S. and Rietbrock, S. (1997). Concentration-effect relationship of delta-9-tetrahydrocannabiol and prediction of psychotropic effects after smoking marijuana. Int.J.Clin.Pharmacol.Ther. 35: 155-159.
152. Johns, A. (2001). Psychiatric effects of cannabis. Br.J.Psychiatry. 178: 116-122.
153. Boyce, A. and McArdle, P. (2007). Long-term effects of cannabis. Pediatrics and child health. 18: 37-41.
154. Zammit, S., Moore, T. H., Lingford-Hughes, A., Barnes, T. R. and others. (2008). Effects of cannabis use on outcomes of psychotic disorders: systematic review. Br.J.Psychiatry. 193: 357-363.
155. Moreira, F. A., Grieb, M., and Lutz, B. (2009). Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: focus on anxiety and depression. Best.Pract.Res.Clin.Endocrinol.Metab. 23: 133144.
156. Vandrey, R. and Haney, M. (2009). Pharmacotherapy for cannabis dependence: how close are we? CNS.Drugs. 23: 543-553.
157. Lal, S., Prasad, N., Ryan, M., Tangri, S. and others. (2011). Cannabis use amongst patients with inflammatory bowel disease. Eur.J.Gastroenterol.Hepatol. 23: 891-896.
158. Fiz, J., Duran, M., Capella, D., Carbonell, J. and others. (2011). Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life. PLoS.One. 6: e18440.-
159. Tramer, M. R., Carroll, D., Campbell, F. A., Reynolds, D. J. and others. (2001). Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 323: 16-21.
160. Corcoran, C. M., Kimhy, D., Stanford, A., Khan, S. and others. (2008). Temporal association of cannabis use with symptoms in individuals at clinical high risk for psychosis. Schizophr.Res. 106: 286-293.
161. Schierenbeck, T., Riemann, D., Berger, M., and Hornyak, M. (2008). Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana. Sleep Med.Rev. 12: 381-389.
162. Hunault, C. C., Mensinga, T. T., Bocker, K. B., Schipper, C. M. and others. (2009). Cognitive and psychomotor effects in males after smoking a combination of tobacco and cannabis containing up to 69 mg delta-9tetrahydrocannabinol (THC). Psychopharmacology (Berl). 204: 85-94.
163. Scott, J., Martin, G., Bor, W., Sawyer, M. and others. (2009). The prevalence and correlates of hallucinations in Australian adolescents: results from a national survey. Schizophr.Res. 107: 179-185.
164. Page, S. A., Verhoef, M. J., Stebbins, R. A., Metz, L. M. and others. (2003). Cannabis use as described by people with multiple sclerosis. Can.J.Neurol.Sci. 30: 201-205.
165. Clark, A. J., Ware, M. A., Yazer, E., Murray, T. J. and others. (2004). Patterns of cannabis use among patients with multiple sclerosis. Neurology. 62: 2098-2100.
166. Haney, M., Rabkin, J., Gunderson, E., and Foltin, R. W. (2005). Dronabinol and marijuana in HIV(+) marijuana smokers: acute effects on caloric intake and mood. Psychopharmacology (Berl). 181: 170-178.
167. Haney, M., Gunderson, E. W., Rabkin, J., Hart, C. L. and others. (2007). Dronabinol and marijuana in HIV-positive marijuana smokers. Caloric intake, mood, and sleep. J.Acquir.Immune.Defic.Syndr. 45: 545-554.
168. Wilsey, B., Marcotte, T., Tsodikov, A., Millman, J. and others. (2008). A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J.Pain. 9: 506-521.
169. Sewell, R. A., Poling, J., and Sofuoglu, M. (2009). The effect of cannabis compared with alcohol on driving. Am.J.Addict. 18: 185-193.
170. Bramness, J. G., Khiabani, H. Z., and Morland, J. (2010). Impairment due to cannabis and ethanol: clinical signs and additive effects. Addiction. 105: 1080-1087.
171. Ronen, A., Chassidim, H. S., Gershon, P., Parmet, Y. and others. (2010). The effect of alcohol, THC and their combination on perceived effects, willingness to drive and performance of driving and non-driving tasks. Accid.Anal.Prev. 42: 1855-1865.
172. Ware, M. A., Wang, T., Shapiro, S., Robinson, A. and others. (2010). Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 182: E694-E701.
173. Lynch, M. E. and Campbell, F. (2011). Cannabinoids for Treatment of Chronic Non-Cancer Pain; a Systematic Review of Randomized Trials. Br.J.Clin.Pharmacol. 72: 735-744.
174. Abbott Products Inc. Marinol Product Monograph. 2010.
175. Asbridge, M., Hayden, J. A., and Cartwright, J. L. (2012). Acute cannabis consumption and motor vehicle collision risk: systematic review of observational studies and meta-analysis. BMJ. 344: e536-
176. Downey, L. A., King, R., Papafotiou, K., Swann, P. and others. (2012). The effects of cannabis and alcohol on simulated driving: Influences of dose and experience. Accid.Anal.Prev. 50: 879-886.
177. Elvik, R. (2012). Risk of road accident associated with the use of drugs: A systematic review and meta-analysis of evidence from epidemiological studies (in press). Accid.Anal.Prev.
178. Honarmand, K., Tierney, M. C., O’Connor, P., and Feinstein, A. (2011). Effects of cannabis on cognitive function in patients with multiple sclerosis. Neurology. 76: 1153-1160.
179. Pope, H. G., Jr., Gruber, A. J., Hudson, J. I., Huestis, M. A. and others. (2002). Cognitive measures in long-term cannabis users. J.Clin.Pharmacol. 42: 41S-47S.
180. Solowij, N., Stephens, R. S., Roffman, R. A., Babor, T. and others. (2002). Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA. 287: 1123-1131.
181. Ilan, A. B., Smith, M. E., and Gevins, A. (2004). Effects of marijuana on neurophysiological signals of working and episodic memory. Psychopharmacology (Berl). 176: 214-222.
182. Williamson, E. M. and Evans, F. J. (2000). Cannabinoids in clinical practice. Drugs. 60: 1303-1314.
183. Weinstein, A., Brickner, O., Lerman, H., Greemland, M. and others. (2008). Brain imaging study of the acute effects of Delta9-tetrahydrocannabinol (THC) on attention and motor coordination in regular users of marijuana. Psychopharmacology (Berl). 196: 119-131.
184. Greenwald, M. K. and Stitzer, M. L. (2000). Antinociceptive, subjective and behavioral effects of smoked marijuana in humans. Drug Alcohol Depend. 59: 261-275.
185. Wallace, M., Schulteis, G., Atkinson, J. H., Wolfson, T. and others. (2007). Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology. 107: 785-796.
186. Ellis, R. J., Toperoff, W., Vaida, F., van den Brande, G. and others. (2009). Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology. 34: 672-680.
187. Abrams, D. I., Couey, P., Shade, S. B., Kelly, M. E. and others. (2011). Cannabinoid-opioid interaction in chronic pain. Clin.Pharmacol.Ther. 90: 844-851.
188. Corey-Bloom, J., Wolfson, T., Gamst, A., Jin, S. and others. (2012). Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ. 184: 1143-1150.
189. Lahat, A., Lang, A., and Ben-Horin, S. (2012). Impact of cannabis treatment on the quality of life, weight and clinical disease activity in inflammatory bowel disease patients: a pilot prospective study. Digestion. 85: 18.
190. Lynch, M. E., Young, J., and Clark, A. J. (2006). A case series of patients using medicinal marihuana for management of chronic pain under the Canadian Marihuana Medical Access Regulations. J.Pain Symptom.Manage. 32: 497-501.
191. Musty, R and Rossi, R. (2001). Effects of smoked cannabis and oral delta-9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: A review of state clinical trials. Journal of Cannabis Therapeutics. 1: 29-42.
192. Soderpalm, A. H., Schuster, A., and de, Wit H. (2001). Antiemetic efficacy of smoked marijuana: subjective and behavioral effects on nausea induced by syrup of ipecac. Pharmacol.Biochem.Behav. 69: 343-350.
193. Bedi, G., Foltin, R. W., Gunderson, E. W., Rabkin, J. and others. (2010). Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study. Psychopharmacology (Berl). 212: 675-686.
194. Sannarangappa, V. and Tan, C. (2009). Cannabinoid hyperemesis. Intern.Med.J. 39: 777-778.
195. Donnino, M. W., Cocchi, M. N., Miller, J., and Fisher, J. (2011). Cannabinoid hyperemesis: a case series. J.Emerg.Med. 40: e63-e66.
196. Sullivan, S. (2010). Cannabinoid hyperemesis. Can.J.Gastroenterol. 24: 284-285.
197. Miller, J. B., Walsh, M., Patel, P. A., Rogan, M. and others. (2010). Pediatric cannabinoid hyperemesis: two cases. Pediatr.Emerg.Care. 26: 919-920.
198. Patterson, D. A., Smith, E., Monahan, M., Medvecz, A. and others. (2010). Cannabinoid hyperemesis and compulsive bathing: a case series and paradoxical pathophysiological explanation. J.Am.Board Fam.Med. 23: 790-793.
199. Choung, R. S., Locke, G. R., III, Lee, R. M., Schleck, C. D. and others. (2012). Cyclic vomiting syndrome and functional vomiting in adults: association with cannabinoid use in males. Neurogastroenterol.Motil. 24: 206, e1.
200. Francis, H. (2011). Emerging role of chronic cannabis usage and hyperemesis syndrome. South.Med.J. 104: 665-
201. Schmid, S. M., Lapaire, O., Huang, D. J., Jurgens, F. E. and others. (2011). Cannabinoid hyperemesis syndrome: an underreported entity causing nausea and vomiting of pregnancy. Arch.Gynecol.Obstet. 284: 1095-1097.
202. Wallace, E. A., Andrews, S. E., Garmany, C. L., and Jelley, M. J. (2011). Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and treatment algorithm. South.Med.J. 104: 659-664.
203. Simonetto, D. A., Oxentenko, A. S., Herman, M. L., and Szostek, J. H. (2012). Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin.Proc. 87: 114-119.
204. Wild, K. and Wilson, H. (2012). Cannabinoid hyperemesis. Emerg.Med.J. 29: 67-69.
205. Foltin, R. W., Fischman, M. W., and Byrne, M. F. (1988). Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory. Appetite. 11: 1-14.
206. Mattes, R. D., Engelman, K., Shaw, L. M., and Elsohly, M. A. (1994). Cannabinoids and appetite stimulation. Pharmacol.Biochem.Behav. 49: 187-195.
207. Haney, M., Ward, A. S., Comer, S. D., Foltin, R. W. and others. (1999). Abstinence symptoms following oral THC administration to humans. Psychopharmacology (Berl). 141: 385-394.
208. Sutton, I. R. and Daeninck, P. (2006). Cannabinoids in the management of intractable chemotherapy-induced nausea and vomiting and cancer-related pain. J.Support.Oncol. 4: 531-535.
209. Pisanti, S., Malfitano, A. M., Grimaldi, C., Santoro, A. and others. (2009). Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents. Best.Pract.Res.Clin.Endocrinol.Metab. 23: 117-131.
210. Lichtman, A. H. and Martin, B. R. (2005). Cannabinoid tolerance and dependence. Handb.Exp.Pharmacol. 691-717.
211. Gonzalez, S., Cebeira, M., and Fernandez-Ruiz, J. (2005). Cannabinoid tolerance and dependence: a review of studies in laboratory animals. Pharmacol.Biochem.Behav. 81: 300-318.
212. Jones, R. T., Benowitz, N., and Bachman, J. (1976). Clinical studies of cannabis tolerance and dependence. Ann.N.Y.Acad.Sci. 282: 221-239.
213. Compton, D. R., Dewey, W. L., and Martin, B. R. (1990). Cannabis dependence and tolerance production. Adv.Alcohol Subst.Abuse. 9: 129-147.
214. Pertwee, R. Tolerance to and dependence on psychotropic cannabinoids. The biological bases of drug tolerance and dependence. Pratt, J. London: Academic Press, 1991.
215. De Vry, J., Jentzsch, K. R., Kuhl, E., and Eckel, G. (2004). Behavioral effects of cannabinoids show differential sensitivity to cannabinoid receptor blockade and tolerance development. Behav.Pharmacol. 15: 1-12.
216. D’Souza, D. C., Ranganathan, M., Braley, G., Gueorguieva, R. and others. (2008). Blunted psychotomimetic and amnestic effects of delta-9-tetrahydrocannabinol in frequent users of cannabis. Neuropsychopharmacology. 33: 2505-2516.
217. Rog, D. J., Nurmikko, T. J., and Young, C. A. (2007). Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin.Ther. 29: 2068-2079.
218. Serpell, M. G., Notcutt, W., and Collin, C. (2012). Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J.Neurol. 260: 285-295.
219. Hall, W. and Solowij, N. The adverse health and psychological consequences of cannabis dependence. Cannabis dependence. Roffman, R. A. and Stephens, R. S. Cambridge: Cambridge University Press, 2006.
220. Kalant, H. (2004). Adverse effects of cannabis on health: an update of the literature since 1996. Prog.Neuropsychopharmacol.Biol.Psychiatry. 28: 849-863.
221. Cooper, Z. D. and Haney, M. (2008). Cannabis reinforcement and dependence: role of the cannabinoid CB1 receptor. Addict.Biol. 13: 188-195.
222. Allsop, D. J., Norberg, M. M., Copeland, J., Fu, S. and others. (2011). The Cannabis Withdrawal Scale development: patterns and predictors of cannabis withdrawal and distress. Drug Alcohol Depend. 119: 123-129.
223. Renault, P. F., Schuster, C. R., Heinrich, R., and Freeman, D. X. (1971). Marihuana: standardized smoke administration and dose effect curves on heart rate in humans. Science. 174: 589-591.
224. Clark, S. C., Greene, C., Karr, G. W., MacCannell, K. L. and others. (1974). Cardiovascular effects of marihuana in man. Can.J.Physiol Pharmacol. 52: 706-719.
225. O’Leary, D. S., Block, R. I., Koeppel, J. A., Flaum, M. and others. (2002). Effects of smoking marijuana on brain perfusion and cognition. Neuropsychopharmacology. 26: 802-816.
226. Trouve, R. and Nahas, G. Cardiovascular effects of marihuana and cannabinoids. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
227. Jones, R. T. (2002). Cardiovascular system effects of marijuana. J.Clin.Pharmacol. 42: 58S-63S.
228. Hollister, L. E. (1986). Health aspects of cannabis. Pharmacol.Rev. 38: 1-20.
229. Miller, R. H., Dhingra, R. C., Kanakis, C., Jr., Leon, F. and others. (1977). The electrophysiological effects of delta9-tetrahydrocannabinol (cannabis) on cardiac conduction in man. Am.Heart J. 94: 740-747.
230. Lindsay, A. C., Foale, R. A., Warren, O., and Henry, J. A. (2005). Cannabis as a precipitant of cardiovascular emergencies. Int.J.Cardiol. 104: 230-232.
231. Beaconsfield, P. (1974). Some cardiovascular effects of cannabis. Am.Heart J. 87: 143-146.
232. Mittleman, M. A., Lewis, R. A., Maclure, M., Sherwood, J. B. and others. (2001). Triggering myocardial infarction by marijuana. Circulation. 103: 2805-2809.
233. Mathew, R. J., Wilson, W. H., and Davis, R. (2003). Postural syncope after marijuana: a transcranial Doppler study of the hemodynamics. Pharmacol.Biochem.Behav. 75: 309-318.
234. Gorelick, D. A. and Heishman, S. J. (2006). Methods for clinical research involving cannabis administration. Methods Mol.Med. 123: 235-253.
235. Lundqvist, T. (2005). Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions. Pharmacol.Biochem.Behav. 81: 319-330.
236. Singh, N. N., Pan, Y., Muengtaweeponsa, S., Geller, T. J. and others. (2012). Cannabis-related stroke: case series and review of literature. J.Stroke Cerebrovasc.Dis. 21: 555-560.
237. Renard, D., Taieb, G., Gras-Combe, G., and Labauge, P. (2012). Cannabis-related myocardial infarction and cardioembolic stroke. J.Stroke Cerebrovasc.Dis. 21: 82-83.
238. Sidney, S., Quesenberry Jr, C. P., Friedman, G. D., and Tekawa, I. S. (1997). Marijuana use and cancer incidence (California, United States). Cancer Causes Control. 8: 722-728.
239. Zhang, Z. F., Morgenstern, H., Spitz, M. R., Tashkin, D. P. and others. (1999). Marijuana use and increased risk of squamous cell carcinoma of the head and neck. Cancer Epidemiol.Biomarkers Prev. 8: 1071-1078.
240. Hashibe, M., Morgenstern, H., Cui, Y., Tashkin, D. P. and others. (2006). Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiol.Biomarkers Prev. 15: 1829-1834.
241. Aldington, S., Harwood, M., Cox, B., Weatherall, M. and others. (2008). Cannabis use and risk of lung cancer: a case-control study. Eur.Respir.J. 31: 280-286.
242. Fligiel, S. E., Roth, M. D., Kleerup, E. C., Barsky, S. H. and others. (1997). Tracheobronchial histopathology in habitual smokers of cocaine, marijuana, and/or tobacco. Chest. 112: 319-326.
243. Tetrault, J. M., Crothers, K., Moore, B. A., Mehra, R. and others. (2007). Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch.Intern.Med. 167: 221-228.
244. Bloom, J. W., Kaltenborn, W. T., Paoletti, P., Camilli, A. and others. (1987). Respiratory effects of non-tobacco cigarettes. Br.Med.J.(Clin.Res.Ed). 295: 1516-1518.
245. Tashkin, D. P., Coulson, A. H., Clark, V. A., Simmons, M. and others. (1987). Respiratory symptoms and lung function in habitual heavy smokers of marijuana alone, smokers of marijuana and tobacco, smokers of tobacco alone, and nonsmokers. Am.Rev.Respir.Dis. 135: 209-216.
246. Roth, M. D., Arora, A., Barsky, S. H., Kleerup, E. C. and others. (1998). Airway inflammation in young marijuana and tobacco smokers. Am.J.Respir.Crit Care Med. 157: 928-937.
247. Pletcher, M. J., Vittinghoff, E., Kalhan, R., Richman, J. and others. (2012). Association between marijuana exposure and pulmonary function over 20 years. JAMA. 307: 173-181.
248. Naftali, T., Lev, L. B., Yablecovitch, D., Half, E. and others. (2011). Treatment of Crohn’s disease with cannabis: an observational study. Isr.Med.Assoc.J. 13: 455-458.
249. Patsenker, E., Stoll, M., Millonig, G., Agaimy, A. and others. (2011). Cannabinoid receptor type I modulates alcohol-induced liver fibrosis. Mol.Med. 17: 1285-1294.
250. Trebicka, J., Racz, I., Siegmund, S. V., Cara, E. and others. (2011). Role of cannabinoid receptors in alcoholic hepatic injury: steatosis and fibrogenesis are increased in CB2 receptor-deficient mice and decreased in CB1 receptor knockouts. Liver Int. 31: 860-870.
251. Reichenbach, V., Ros, J., Fernandez-Varo, G., Casals, G. and others. (2012). Prevention of fibrosis progression in CCl4-treated rats: role of the hepatic endocannabinoid and apelin systems. J.Pharmacol.Exp.Ther. 340: 629-637.
252. Sylvestre, D. L., Clements, B. J., and Malibu, Y. (2006). Cannabis use improves retention and virological outcomes in patients treated for hepatitis C. Eur.J.Gastroenterol.Hepatol. 18: 1057-1063.
253. Grant, P. and Gandhi, P. (2004). A case of cannabis-induced pancreatitis. JOP. 5: 41-43.
254. Wargo, K. A., Geveden, B. N., and McConnell, V. J. (2007). Cannabinoid-induced pancreatitis: a case series. JOP. 8: 579-583.
255. Bournet, B. and Buscail, L. (2008). [Cannabis: a rare cause of acute pancreatitis]. Gastroenterol.Clin.Biol. 32: 922923.
256. Belze, O., Jr., Legras, A., Ehrmann, S., Garot, D. and others. (2011). Cannabis-induced acute pancreatitis. Am.J.Emerg.Med. 29: 131-134.
257. Cox, M. L., Haller, V. L., and Welch, S. P. (2007). Synergy between delta9-tetrahydrocannabinol and morphine in the arthritic rat. Eur.J.Pharmacol. 567: 125-130.
258. Smith, F. L., Fujimori, K., Lowe, J., and Welch, S. P. (1998). Characterization of delta9-tetrahydrocannabinol and anandamide antinociception in nonarthritic and arthritic rats. Pharmacol.Biochem.Behav. 60: 183-191.
259. Blake, D. R., Robson, P., Ho, M., Jubb, R. W. and others. (2006). Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology.(Oxford). 45: 50-52.
260. Schley, M., Legler, A., Skopp, G., Schmelz, M. and others. (2006). Delta-9-THC based monotherapy in fibromyalgia patients on experimentally induced pain, axon reflex flare, and pain relief. Curr.Med.Res.Opin. 22: 12691276.
261. Weber, J., Schley, M., Casutt, M., Gerber, H. and others. (2009). Tetrahydrocannabinol (Delta 9-THC) Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey. Anesthesiol.Res.Pract. 2009: 827290.-
262. Zajicek, J., Fox, P., Sanders, H., Wright, D. and others. (2003). Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 362: 1517-1526.
263. Nogueira-Filho, Gda R., Cadide, T., Rosa, B. T., Neiva, T. G. and others. (2008). Cannabis sativa smoke inhalation decreases bone filling around titanium implants: a histomorphometric study in rats. Implant.Dent. 17: 461470.
264. Tomida, I., Azuara-Blanco, A., House, H., Flint, M. and others. (2006). Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J.Glaucoma. 15: 349-353.
265. Tomida, I., Pertwee, R. G., and zuara-Blanco, A. (2004). Cannabinoids and glaucoma. Br.J.Ophthalmol. 88: 708713.
266. Tanasescu, R. and Constantinescu, C. S. (2010). Cannabinoids and the immune system: an overview. Immunobiology. 215: 588-597.
267. Nahas, G. G., Frick, H. C., Lattimer, J. K., Latour, C. and others. (2002). Pharmacokinetics of THC in brain and testis, male gametotoxicity and premature apoptosis of spermatozoa. Hum.Psychopharmacol. 17: 103-113.
268. Sadeu, J. C., Hughes, C. L., Agarwal, S., and Foster, W. G. (2010). Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications. Crit Rev.Toxicol. 40: 633-652.
269. Gorzalka, B. B., Hill, M. N., and Chang, S. C. (2010). Male-female differences in the effects of cannabinoids on sexual behavior and gonadal hormone function. Horm.Behav. 58: 91-99.
270. Brown, T. T. and Dobs, A. S. (2002). Endocrine effects of marijuana. J.Clin.Pharmacol. 42: 90S-96S.
271. Shamloul, R. and Bella, A. J. (2011). Impact of cannabis use on male sexual health. J.Sex Med. 8: 971-975.
272. Agurell, S., Halldin, M., Lindgren, J. E., Ohlsson, A. and others. (1986). Pharmacokinetics and metabolism of delta 1-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacol.Rev. 38: 21-43.
273. Abrams, D. I., Vizoso, H. P., Shade, S. B., Jay, C. and others. (2007). Vaporization as a Smokeless Cannabis Delivery System: A Pilot Study. Clin.Pharmacol.Ther. 82: 572-578.
274. McClure, E. A., Stitzer, M. L., and Vandrey, R. (2012). Characterizing smoking topography of cannabis in heavy users. Psychopharmacology (Berl). 220: 309-318.
275. Grotenhermen, F. (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clin.Pharmacokinet. 42: 327360.
276. Huestis, M. A. (2005). Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb.Exp.Pharmacol. 657-690.
277. Carter, G. T., Weydt, P., Kyashna-Tocha, M., and Abrams, D. I. (2004). Medicinal cannabis: rational guidelines for dosing. IDrugs. 7: 464-470.
278. Ohlsson, A., Lindgren, J. E., Wahlen, A., Agurell, S. and others. (1980). Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin.Pharmacol.Ther. 28: 409-416.
279. Cooper, Z. D. and Haney, M. (2009). Comparison of subjective, pharmacokinetic, and physiological effects of marijuana smoked as joints and blunts. Drug Alcohol Depend. 103: 107-113.
280. Schwope, D. M., Bosker, W. M., Ramaekers, J. G., Gorelick, D. A. and others. (2012). Psychomotor performance, subjective and physiological effects and whole blood Delta(9)-tetrahydrocannabinol concentrations in heavy, chronic cannabis smokers following acute smoked cannabis. J.Anal.Toxicol. 36: 405-412.
281. Gieringer, D. H. (2001). Cannabis “Vaporization”. Journal of Cannabis Therapeutics. 1: 153-170.
282. Gieringer, D., St Laurent, J., and Goodrich, S. (2004). Cannabis vaporizer combines efficient delivery of THC with effective suppression of pyrolytic compounds. Journal of Cannabis Therapeutics. 4: 7-27.
283. Hazekamp, A., Ruhaak, R., Zuurman, L., van, Gerven J. and others. (2006). Evaluation of a vaporizing device (Volcano) for the pulmonary administration of tetrahydrocannabinol. J.Pharm.Sci. 95: 1308-1317.
284. Pomahacova, B., Van der Kooy, F., and Verpoorte, R. (2009). Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa. Inhal.Toxicol. 21: 1108-1112.
285. Walsh, D., Nelson, K. A., and Mahmoud, F. A. (2003). Established and potential therapeutic applications of cannabinoids in oncology. Support.Care Cancer. 11: 137-143.
286. Cone, E. J., Johnson, R. E., Paul, B. D., Mell, L. D. and others. (1988). Marijuana-laced brownies: behavioral effects, physiologic effects, and urinalysis in humans following ingestion. J.Anal.Toxicol. 12: 169-175.
287. Iversen, L. L. The pharmacology of THC, the psychoactive ingredient in cannabis. The science of marijuana. New York, New York; Oxford University Press, 2000.
288. Schwilke, E. W., Schwope, D. M., Karschner, E. L., Lowe, R. H. and others. (2009). Delta9-tetrahydrocannabinol (THC), 11-hydroxy-THC, and 11-nor-9-carboxy-THC plasma pharmacokinetics during and after continuous high-dose oral THC. Clin.Chem. 55: 2180-2189.
289. Office of Medicinal Cannabis, The Netherlands Ministry of Health Welfare and Sports. Medicinal Cannabis, Information for Health Care Professionals. 2008.
290. GW Pharmaceuticals. Sativex Product Monograph. 2010.
291. Wade, D. T., Makela, P., Robson, P., House, H. and others. (2004). Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebocontrolled study on 160 patients. Mult.Scler. 10: 434-441.
292. Nurmikko, T. J., Serpell, M. G., Hoggart, B., Toomey, P. J. and others. (2007). Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 133: 210-220.
293. Brenneisen, R., Egli, A., Elsohly, M. A., Henn, V. and others. (1996). The effect of orally and rectally administered delta 9-tetrahydrocannabinol on spasticity: a pilot study with 2 patients. Int.J.Clin.Pharmacol.Ther. 34: 446-452.
294. Mattes, R. D., Shaw, L. M., Edling-Owens, J., Engelman, K. and others. (1993). Bypassing the first-pass effect for the therapeutic use of cannabinoids. Pharmacol.Biochem.Behav. 44: 745-747.
295. Perlin, E., Smith, C. G., Nichols, A. I., Almirez, R. and others. (1985). Disposition and bioavailability of various formulations of tetrahydrocannabinol in the rhesus monkey. J.Pharm.Sci. 74: 171-174.
296. Elsohly, M. A., Little, T. L., Jr., Hikal, A., Harland, E. and others. (1991). Rectal bioavailability of delta-9tetrahydrocannabinol from various esters. Pharmacol.Biochem.Behav. 40: 497-502.
297. Elsohly, M. A., Stanford, D. F., Harland, E. C., Hikal, A. H. and others. (1991). Rectal bioavailability of delta-9tetrahydrocannabinol from the hemisuccinate ester in monkeys. J.Pharm.Sci. 80: 942-945.
298. Valiveti, S., Hammell, D. C., Earles, D. C., and Stinchcomb, A. L. (2004). Transdermal delivery of the synthetic cannabinoid WIN 55,212-2: in vitro/in vivo correlation. Pharm.Res. 21: 1137-1145.
299. Valiveti, S., Kiptoo, P. K., Hammell, D. C., and Stinchcomb, A. L. (2004). Transdermal permeation of WIN 55,2122 and CP 55,940 in human skin in vitro. Int.J.Pharm. 278: 173-180.
300. Stinchcomb, A. L., Valiveti, S., Hammell, D. C., and Ramsey, D. R. (2004). Human skin permeation of Delta8tetrahydrocannabinol, cannabidiol and cannabinol. J.Pharm.Pharmacol. 56: 291-297.
301. Harvey, D. J. Absorption, distribution and biotransformation of the cannabinoids. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
302. Widman, M., Agurell, S., Ehrnebo, M., and Jones, G. (1974). Binding of (+)- and (minus)-delta-1tetrahydrocannabinols and (minus)-7-hydroxy-delta-1-tetrahydrocannabinol to blood cells and plasma proteins in man. J.Pharm.Pharmacol. 26: 914-916.
303. Garrett, E. R. and Hunt, C. A. (1977). Pharmacokinetics of delta9-tetrahydrocannabinol in dogs. J.Pharm.Sci. 66: 395-407.
304. Wahlqvist, M., Nilsson, I. M., Sandberg, F., and Agurell, S. (1970). Binding of delta-1-tetrahydrocannabinol to human plasma proteins. Biochem.Pharmacol. 19: 2579-2584.
305. Widman, M., Nilsson, I. M., Agurell, S., Borg, H. and others. (1973). Plasma protein binding of 7-hydroxy- 1tetrahydrocannabinol: an active 1-tetrahydrocannabinol metabolite. J.Pharm.Pharmacol. 25: 453-457.
306. Truitt, E. B., Jr. (1971). Biological disposition of tetrahydrocannabinols. Pharmacol.Rev. 23: 273-278.
307. Nahas, G. G. (2001). The pharmacokinetics of THC in fat and brain: resulting functional responses to marihuana smoking. Hum.Psychopharmacol. 16: 247-255.
308. Schou, J., Prockop, L. D., Dahlstrom, G., and Rohde, C. (1977). Penetration of delta-9-tetrahydrocannabinol and 11OH-delta-9-tetrahydrocannabinol through the blood-brain barrier. Acta Pharmacol.Toxicol.(Copenh). 41: 33-38.
309. Mura, P., Kintz, P., Dumestre, V., Raul, S. and others. (2005). THC can be detected in brain while absent in blood. J.Anal.Toxicol. 29: 842-843.
310. Gunasekaran, N., Long, L. E., Dawson, B. L., Hansen, G. H. and others. (2009). Reintoxication: the release of fatstored delta(9)-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure. Br.J.Pharmacol. 158: 1330-1337.
311. Lemberger, L. (1973). Tetrahydrocannabinol metabolism in man. Drug Metab Dispos. 1: 461-468.
312. Wall, M. E., Sadler, B. M., Brine, D., Taylor, H. and others. (1983). Metabolism, disposition, and kinetics of delta-9tetrahydrocannabinol in men and women. Clin.Pharmacol.Ther. 34: 352-363.
313. Christensen, H. D., Freudenthal, R. I., Gidley, J. T., Rosenfeld, R. and others. (1971). Activity of delta8- and delta9tetrahydrocannabinol and related compounds in the mouse. Science. 172: 165-167.
314. Perez-Reyes, M., Timmons, M. C., Lipton, M. A., Davis, K. H. and others. (1972). Intravenous injection in man of 9 -tetrahydrocannabinol and 11-OH- 9 -tetrahydrocannabinol. Science. 177: 633-635.
315. Huestis, M. A., Mitchell, J. M., and Cone, E. J. (1996). Urinary excretion profiles of 11-nor-9-carboxy-delta 9tetrahydrocannabinol in humans after single smoked doses of marijuana. J.Anal.Toxicol. 20: 441-452.
316. Hawks, R. L. (1982). The constituents of cannabis and the disposition and metabolism of cannabinoids. NIDA Res.Monogr. 42: 125-137.
317. Martin, B. R. and Cone, E. J. Chemistry and pharmacology of cannabis. The Health Effects of Cannabis. Kalant, H., Corrigall, W., Hall, W., and Smart, R. Toronto, Canada: Centre of Addiction and Mental Health, 1999.
318. Sachse-Seeboth, C., Pfeil, J., Sehrt, D., Meineke, I. and others. (2009). Interindividual variation in the pharmacokinetics of Delta9-tetrahydrocannabinol as related to genetic polymorphisms in CYP2C9. Clin.Pharmacol.Ther. 85: 273-276.
319. Oates, J. A. The science of drug therapy. Goodman and Gilman’s the pharmacological basis of therapeutics. Brunton, L. L., Lazo, J. S., and Parker, K. L. New York: McGraw-Hill, 2006.
320. Graham, M. J. and Lake, B. G. (2008). Induction of drug metabolism: species differences and toxicological relevance. Toxicology. 254: 184-191.
321. Bornheim, L. M., Everhart, E. T., Li, J., and Correia, M. A. (1993). Characterization of cannabidiol-mediated cytochrome P450 inactivation. Biochem.Pharmacol. 45: 1323-1331.
322. Kosel, B. W., Aweeka, F. T., Benowitz, N. L., Shade, S. B. and others. (2002). The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir. AIDS. 16: 543-550.
323. Jusko, W. J., Schentag, J. J., Clark, J. H., Gardner, M. and others. (1978). Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin.Pharmacol.Ther. 24: 405-410.
324. Zullino, D. F., Delessert, D., Eap, C. B., Preisig, M. and others. (2002). Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine. Int.Clin.Psychopharmacol. 17: 141-143.
325. Huestis, M. A., Henningfield, J. E., and Cone, E. J. (1992). Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J.Anal.Toxicol. 16: 276-282.
326. Agurell, S. and Leander, K. (1971). Stability, transfer and absorption of cannabinoid constituents of cannabis (hashish) during smoking. Acta Pharm.Suec. 8: 391-402.
327. Wall, M. E. and Perez-Reyes, M. (1981). The metabolism of delta 9-tetrahydrocannabinol and related cannabinoids in man. J.Clin.Pharmacol. 21: 178S-189S.
328. Huestis, M. A., Sampson, A. H., Holicky, B. J., Henningfield, J. E. and others. (1992). Characterization of the absorption phase of marijuana smoking. Clin.Pharmacol.Ther. 52: 31-41.
329. Johansson, E., Agurell, S., Hollister, L. E., and Halldin, M. M. (1988). Prolonged apparent half-life of delta 1tetrahydrocannabinol in plasma of chronic marijuana users. J.Pharm.Pharmacol. 40: 374-375.
330. Cone, E. J. and Huestis, M. A. (1993). Relating blood concentrations of tetrahydrocannabinol and metabolites to pharmacologic effects and time of marijuana usage. Ther.Drug Monit. 15: 527-532.
331. Toennes, S. W., Ramaekers, J. G., Theunissen, E. L., Moeller, M. R. and others. (2008). Comparison of cannabinoid pharmacokinetic properties in occasional and heavy users smoking a marijuana or placebo joint. J.Anal.Toxicol. 32: 470-477.
332. Valeant Canada. Cesamet Product Monograph. 2009.
333. Hollister, L. E., Gillespie, H. K., Ohlsson, A., Lindgren, J. E. and others. (1981). Do plasma concentrations of delta 9-tetrahydrocannabinol reflect the degree of intoxication? J.Clin.Pharmacol. 21: 171S-177S.
334. Strougo, A., Zuurman, L., Roy, C., Pinquier, J. L. and others. (2008). Modelling of the concentration–effect relationship of THC on central nervous system parameters and heart rate — insight into its mechanisms of action and a tool for clinical research and development of cannabinoids. J.Psychopharmacol. 22: 717-726.
335. Lynch, M. E. and Watson, C. P. (2006). The pharmacotherapy of chronic pain: a review. Pain Res.Manag. 11: 11-38.
336. Wu, D. F., Yang, L. Q., Goschke, A., Stumm, R. and others. (2008). Role of receptor internalization in the agonistinduced desensitization of cannabinoid type 1 receptors. J.Neurochem. 104: 1132-1143.
337. Maldonado, R. (2002). Study of cannabinoid dependence in animals. Pharmacol.Ther. 95: 153-164.
338. Pertwee, R. G. (2009). Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br.J.Pharmacol. 156: 397-411.
339. Hirvonen, J., Goodwin, R. S., Li, C. T., Terry, G. E. and others. (2012). Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers. Mol.Psychiatry. 17: 642-649.
340. Haney, M., Ward, A. S., Comer, S. D., Foltin, R. W. and others. (1999). Abstinence symptoms following smoked marijuana in humans. Psychopharmacology (Berl). 141: 395-404.
341. American Psychiatric Association. Substance-related disorders. Diagnostic and statistical manual of mental disorders text revision (DSM-IV-TR). American Psychiatric Association. Washington, D.C.: American Psychiatric Association, 2000.
342. Budney, A. J., Hughes, J. R., Moore, B. A., and Vandrey, R. (2004). Review of the validity and significance of cannabis withdrawal syndrome. Am.J.Psychiatry. 161: 1967-1977.
343. Hazekamp, A., Bastola, K., Rashidi, H., Bender, J. and others. (2007). Cannabis tea revisited: a systematic evaluation of the cannabinoid composition of cannabis tea. J.Ethnopharmacol. 113: 85-90.
344. Pertwee, R. G. (1974). Tolerance to the effect of delta1-tetrahydrocannabinol on corticosterone levels in mouse plasma produced by repeated administration of cannabis extract or delta1-tetrahydrocannabinol. Br.J.Pharmacol. 51: 391-397.
345. Lozano, I. (2001). The therapeutic uses of Cannabis sativa (L.) in Arabic medicine. Journal of Cannabis Therapeutics. 1: 63-70.
346. Russo, E. History of cannabis as a medicine. The Medicinal Uses of Cannabis and Cannabinoids. Guy, G. W., Whittle, B. A., and Robson, P. J. London: Pharmaceutical Press, 2004.
347. Russo, E. B. (2007). History of cannabis and its preparations in saga, science, and sobriquet. Chem.Biodivers. 4: 1614-1648.
348. Fraser, G. A. (2009). The use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD). CNS.Neurosci.Ther. 15: 84-88.
349. Portenoy, R. K., Ganae-Motan, E. D., Allende, S., Yanagihara, R. and others. (2012). Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J.Pain. 13: 438-449.
350. Ware, M. A., Adams, H., and Guy, G. W. (2005). The medicinal use of cannabis in the UK: results of a nationwide survey. Int.J.Clin.Pract. 59: 291-295.
351. World Health Organization (WHO). Cannabis: a health perspective and research agenda. 1997
352. Cami, J., Guerra, D., Ugena, B., Segura, J. and others. (1991). Effect of subject expectancy on the THC intoxication and disposition from smoked hashish cigarettes. Pharmacol.Biochem.Behav. 40: 115-119.
353. Skrabek, R. Q., Galimova, L., Ethans, K., and Perry, D. (2008). Nabilone for the treatment of pain in fibromyalgia. J.Pain. 9: 164-173.
354. Ware, M. A., Fitzcharles, M. A., Joseph, L., and Shir, Y. (2010). The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth.Analg. 110: 604-610.
355. Kalliomaki, J., Philipp, A., Baxendale, J., Annas, P. and others. (2012). Lack of effect of central nervous systemactive doses of nabilone on capsaicin-induced pain and hyperalgesia. Clin.Exp.Pharmacol.Physiol. 39: 336-342.
356. World Health Organization (WHO). WHO Definition of Palliative Care. 2012.
357. Green, A. J. and De-Vries, K. (2010). Cannabis use in palliative care – an examination of the evidence and the implications for nurses. J.Clin.Nurs. 19: 2454-2462.
358. Gardiner, C. and Ingleton, C. (2010). Commentary on Green AJ & De-Vries K (2010) Cannabis use in palliative care–an examination of the evidence and the implications for nurses. Journal of Clinical Nursing 19, 24542462. J.Clin.Nurs. 19: 3253-3255.
359. Glare, P., Miller, J., Nikolova, T., and Tickoo, R. (2011). Treating nausea and vomiting in palliative care: a review. Clin.Interv.Aging. 6: 243-259.
360. Fine, P. G. (2012). Treatment guidelines for the pharmacological management of pain in older persons. Pain Med. 13 Suppl 2: S57-S66.
361. Svendsen, K. B., Jensen, T. S., and Bach, F. W. (2004). Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ. 329: 253-260.
362. Brisbois, T. D., de Kock, I. H., Watanabe, S. M., Mirhosseini, M. and others. (2011). Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann.Oncol. 22: 2086-2093.
363. Strasser, F., Luftner, D., Possinger, K., Ernst, G. and others. (2006). Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J.Clin.Oncol. 24: 3394-3400.
364. Toth, C., Mawani, S., Brady, S., Chan, C. and others. (2012). An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain. 153: 2073-2082.
365. Selvarajah, D., Gandhi, R., Emery, C. J., and Tesfaye, S. (2010). Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: depression is a major confounding factor. Diabetes Care. 33: 128-130.
366. Novotna, A., Mares, J., Ratcliffe, S., Novakova, I. and others. (2011). A randomized, double-blind, placebocontrolled, parallel-group, enriched-design study of nabiximols* (Sativex((R)) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur.J.Neurol. 18: 1122-1131.
367. Navari, R. M. (2009). Pharmacological management of chemotherapy-induced nausea and vomiting: focus on recent developments. Drugs. 69: 515-533.
368. Hornby, P. J. (2001). Central neurocircuitry associated with emesis. Am.J.Med. 111 Suppl 8A: 106S-112S.
369. Van Sickle, M. D., Duncan, M., Kingsley, P. J., Mouihate, A. and others. (2005). Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science. 310: 329-332.
370. Darmani, N. A. (2001). The cannabinoid CB1 receptor antagonist SR 141716A reverses the antiemetic and motor depressant actions of WIN 55, 212-2. Eur.J.Pharmacol. 430: 49-58.
371. Barann, M., Molderings, G., Bruss, M., Bonisch, H. and others. (2002). Direct inhibition by cannabinoids of human 5-HT3A receptors: probable involvement of an allosteric modulatory site. Br.J.Pharmacol. 137: 589-596.
372. Rock, E. M., Bolognini, D., Limebeer, C. L., Cascio, M. G. and others. (2012). Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. Br.J.Pharmacol. 165: 2620-2634.
373. Rock, E. M., Goodwin, J. M., Limebeer, C. L., Breuer, A. and others. (2011). Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews. Psychopharmacology (Berl). 215: 505-512.
374. Machado Rocha, F. C., Stefano, S. C., De Cassia, Haiek R., Rosa Oliveira, L. M. and others. (2008). Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur.J.Cancer Care (Engl.). 17: 431-443.
375. Meiri, E., Jhangiani, H., Vredenburgh, J. J., Barbato, L. M. and others. (2007). Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr.Med.Res.Opin. 23: 533-543.
376. Kwiatkowska, M., Parker, L. A., Burton, P., and Mechoulam, R. (2004). A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacology (Berl). 174: 254-259.
377. Wang, Y., Ray, A. P., McClanahan, B. A., and Darmani, N. A. (2009). The antiemetic interaction of Delta9tetrahydrocannabinol when combined with tropisetron or dexamethasone in the least shrew. Pharmacol.Biochem.Behav. 91: 367-373.
378. Institute of Medicine. The medical value of marijuana and related substances. Marijuana and medicine: Assessing the science base. Joy, J. E., Watson, S. J., and Benson, J. A. Washington, DC: National Academy Press, 1999.
379. Health Department of New South Wales, Australia. Working Party on the Use of Cannabis for Medical Purposes. (2000). 2.
380. Herrstedt, J. and Dombernowsky, P. (2007). Anti-emetic therapy in cancer chemotherapy: current status. Basic Clin.Pharmacol.Toxicol. 101: 143-150.
381. Canadian Pharmacists Association. Compendium of Pharmaceuticals and Specialties. Ottawa: Canadian Pharmacists Association, 2009.
382. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. 2010.
383. Clary, P. L. and Lawson, P. (2009). Pharmacologic pearls for end-of-life care. Am.Fam.Physician. 79: 1059-1065.
384. Minister of Justice, Government of Canada. Marihuana Medical Access Regulations. 2011.
385. Smit, E. and Crespo, C. J. (2001). Dietary intake and nutritional status of US adult marijuana users: results from the Third National Health and Nutrition Examination Survey. Public Health Nutr. 4: 781-786.
386. Di Marzo, V. and Matias, I. (2005). Endocannabinoid control of food intake and energy balance. Nat.Neurosci. 8: 585-589.
387. Matias, I., Bisogno, T., and Di, Marzo, V. (2006). Endogenous cannabinoids in the brain and peripheral tissues: regulation of their levels and control of food intake. Int.J.Obes.(Lond). 30 Suppl 1: S7-S12.
388. Tibirica, E. (2010). The multiple functions of the endocannabinoid system: a focus on the regulation of food intake. Diabetol.Metab Syndr. 2: 5-10.
389. Farrimond, J. A., Mercier, M. S., Whalley, B. J., and Williams, C. M. (2011). Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation. Phytother.Res. 25: 170-188.
390. Abrams, D. I., Hilton, J. F., Leiser, R. J., Shade, S. B. and others. (2003). Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Ann.Intern.Med. 139: 258266.
391. Ravinet-Trillou, C., Delgorge, C., Menet, C., Arnone, M. and others. (2004). CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int.J.Obes.Relat Metab Disord. 28: 640-648.
392. Timpone, J. G., Wright, D. J., Li, N., Egorin, M. J. and others. (1997). The safety and pharmacokinetics of singleagent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting
syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AIDS Res.Hum.Retroviruses. 13: 305-315.
393. Beal, J. E., Olson, R., Laubenstein, L., Morales, J. O. and others. (1995). Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J.Pain Symptom.Manage. 10: 89-97.
394. Beal, J. E., Olson, R., Lefkowitz, L., Laubenstein, L. and others. (1997). Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. J.Pain Symptom.Manage. 14: 7-14.
395. Tchekmedyian, N. S., Zahyna, D., Halpert, C., and Heber, D. (1992). Clinical aspects of nutrition in advanced cancer. Oncology. 49 Suppl 2: 3-7.
396. Walsh, D., Donnelly, S., and Rybicki, L. (2000). The symptoms of advanced cancer: relationship to age, gender, and performance status in 1,000 patients. Support.Care Cancer. 8: 175-179.
397. Ekert, H., Waters, K. D., Jurk, I. H., Mobilia, J. and others. (1979). Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol. Med.J.Aust. 2: 657-659.
398. Sallan, S. E., Cronin, C., Zelen, M., and Zinberg, N. E. (1980). Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N.Engl.J.Med. 302: 135-138.
399. Plasse, T. F., Gorter, R. W., Krasnow, S. H., Lane, M. and others. (1991). Recent clinical experience with dronabinol. Pharmacol.Biochem.Behav. 40: 695-700.
400. Nelson, K., Walsh, D., Deeter, P., and Sheehan, F. (1994). A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J.Palliat.Care. 10: 14-18.
401. Regelson, W., Butler, J. R., and Schulz, J. Delta-9-tetrahydrocannabinol as an effective antidepressant and appetitestimulating agent in advanced cancer patients. The Pharmacology of marihuana: A monograph of the National Institute on Drug Abuse. Braude, M. and Szara, S. New York: Raven Press, 1976.
402. Jatoi, A., Windschitl, H. E., Loprinzi, C. L., Sloan, J. A. and others. (2002). Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J.Clin.Oncol. 20: 567-573.
403. Mantovani, G., Maccio, A., Madeddu, C., Serpe, R. and others. (2010). Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist. 15: 200-211.
404. Monteleone, P., Matias, I., Martiadis, V., De, Petrocellis L. and others. (2005). Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa. Neuropsychopharmacology. 30: 1216-1221.
405. Siegfried, Z., Kanyas, K., Latzer, Y., Karni, O. and others. (2004). Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: differences between restricting and binging/purging subtypes. Am.J.Med.Genet.B Neuropsychiatr.Genet. 125B: 126-130.
406. Muller, T. D., Reichwald, K., Bronner, G., Kirschner, J. and others. (2008). Lack of association of genetic variants in genes of the endocannabinoid system with anorexia nervosa. Child Adolesc.Psychiatry Ment.Health. 2: 3339.
407. Lewis, D. Y. and Brett, R. R. (2010). Activity-based anorexia in C57/BL6 mice: effects of the phytocannabinoid, Delta9-tetrahydrocannabinol (THC) and the anandamide analogue, OMDM-2. Eur.Neuropsychopharmacol. 20: 622-631.
408. Verty, A. N., Evetts, M. J., Crouch, G. J., McGregor, I. S. and others. (2011). The cannabinoid receptor agonist THC attenuates weight loss in a rodent model of activity-based anorexia. Neuropsychopharmacology. 36: 13491358.
409. Gross, H., Ebert, M. H., Faden, V. B., Goldberg, S. C. and others. (1983). A double-blind trial of delta 9tetrahydrocannabinol in primary anorexia nervosa. J.Clin.Psychopharmacol. 3: 165-171.
410. Volicer, L., Stelly, M., Morris, J., McLaughlin, J. and others. (1997). Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int.J.Geriatr.Psychiatry. 12: 913-919.
411. American Medical Association, Council of Scientific Affairs. Medical Marijuana. Internet. American Medical Association, Council of Scientific Affairs. 1997.
412. Aggarwal, S. K., Carter, G. T., Sullivan, M. D., ZumBrunnen, C. and others. (2009). Characteristics of patients with chronic pain accessing treatment with medical cannabis in Washington State. J.Opioid.Manag. 5: 257-286.
413. Heutink, M., Post, M. W., Wollaars, M. M., and van Asbeck, F. W. (2011). Chronic spinal cord injury pain: pharmacological and non-pharmacological treatments and treatment effectiveness. Disabil.Rehabil. 33: 433-440.
414. Baker, D., Pryce, G., Croxford, J. L., Brown, P. and others. (2000). Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature. 404: 84-87.
415. Centonze, D., Rossi, S., Finazzi-Agro, A., Bernardi, G. and others. (2007). The (endo)cannabinoid system in multiple sclerosis and amyotrophic lateral sclerosis. Int.Rev.Neurobiol. 82: 171-186.
416. Di Filippo, M., Pini, L. A., Pelliccioli, G. P., Calabresi, P. and others. (2008). Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis. J.Neurol.Neurosurg.Psychiatry. 79: 1224-1229.
417. Jean-Gilles, L., Feng, S., Tench, C. R., Chapman, V. and others. (2009). Plasma endocannabinoid levels in multiple sclerosis. J.Neurol.Sci. 287: 212-215.
418. Pertwee, R. G. (2007). Cannabinoids and multiple sclerosis. Mol.Neurobiol. 36: 45-59.
419. Lyman, W. D., Sonett, J. R., Brosnan, C. F., Elkin, R. and others. (1989). Delta 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis. J.Neuroimmunol. 23: 73-81.
420. Maresz, K., Pryce, G., Ponomarev, E. D., Marsicano, G. and others. (2007). Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat.Med. 13: 492-497.
421. Pryce, G. and Baker, D. (2007). Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2, cannabinoid receptors. Br.J.Pharmacol. 150: 519-525.
422. Croxford, J. L., Pryce, G., Jackson, S. J., Ledent, C. and others. (2008). Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. J.Neuroimmunol. 193: 120-129.
423. Baker, D., Jackson, S. J., and Pryce, G. (2007). Cannabinoid control of neuroinflammation related to multiple sclerosis. Br.J.Pharmacol. 152: 649-654.
424. Sanchez, A. J. and Garcia-Merino, A. (2011). Neuroprotective agents: Cannabinoids. Clin.Immunol. 142: 57-67.
425. Consroe, P. and Sandyk, R. Therapeutic potential of cannabinoids in neurological disorders. Marijuana/Cannabinoids as therapeutic agents. Mechoulam, R. Boca Raton, FL: CRC Press, 1986.
426. Chong, M. S., Wolff, K., Wise, K., Tanton, C. and others. (2006). Cannabis use in patients with multiple sclerosis. Mult.Scler. 12: 646-651.
427. Zajicek, J. P., Sanders, H. P., Wright, D. E., Vickery, P. J. and others. (2005). Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J.Neurol.Neurosurg.Psychiatry. 76: 1664-1669.
428. Vaney, C., Heinzel-Gutenbrunner, M., Jobin, P., Tschopp, F. and others. (2004). Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult.Scler. 10: 417-424.
429. Wade, D. T., Makela, P. M., House, H., Bateman, C. and others. (2006). Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult.Scler. 12: 639-645.
430. Collin, C., Davies, P., Mutiboko, I. K., and Ratcliffe, S. (2007). Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur.J.Neurol. 14: 290-296.
431. Hobart, J. C., Riazi, A., Thompson, A. J., Styles, I. M. and others. (2006). Getting the measure of spasticity in multiple sclerosis: the Multiple Sclerosis Spasticity Scale (MSSS-88). Brain. 129: 224-234.
432. Zajicek, J. P., Hobart, J. C., Slade, A., Barnes, D. and others. (2012). MUltiple Sclerosis and Extract of Cannabis: results of the MUSEC trial. J.Neurol.Neurosurg.Psychiatry. 83: 1125-1132.
433. Killestein, J., Hoogervorst, E. L., Reif, M., Kalkers, N. F. and others. (2002). Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology. 58: 1404-1407.
434. Aragona, M., Onesti, E., Tomassini, V., Conte, A. and others. (2009). Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study. Clin.Neuropharmacol. 32: 41-47.
435. Freeman, R. M., Adekanmi, O., Waterfield, M. R., Waterfield, A. E. and others. (2006). The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS). Int.Urogynecol.J.Pelvic.Floor.Dysfunct. 17: 636-641.
436. Sliwa, J. A., Bell, H. K., Mason, K. D., Gore, R. M. and others. (1996). Upper urinary tract abnormalities in multiple sclerosis patients with urinary symptoms. Arch.Phys.Med.Rehabil. 77: 247-251.
437. Consroe, P., Musty, R., Rein, J., Tillery, W. and others. (1997). The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur.Neurol. 38: 44-48.
438. Brady, C. M., DasGupta, R., Dalton, C., Wiseman, O. J. and others. (2004). An open-label pilot study of cannabisbased extracts for bladder dysfunction in advanced multiple sclerosis. Mult.Scler. 10: 425-433.
439. Rossi, S., Bernardi, G., and Centonze, D. (2010). The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis. Exp.Neurol. 224: 92-102.
440. Scotter, E. L., Abood, M. E., and Glass, M. (2010). The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br.J.Pharmacol. 160: 480-498.
441. Amtmann, D., Weydt, P., Johnson, K. L., Jensen, M. P. and others. (2004). Survey of cannabis use in patients with amyotrophic lateral sclerosis. Am.J.Hosp.Palliat.Care. 21: 95-104.
442. Weber, M., Goldman, B., and Truniger, S. (2010). Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: a randomised, double-blind crossover trial. J.Neurol.Neurosurg.Psychiatry. 81: 1135-1140.
443. Gelinas, D. F, Miller, R. G, and Abood, M. (2002). Pilot study of safety and tolerability of delta 9-THC (Marinol) treatment for ALS. Amyotroph Lateral Scler Other Motor Neuron Disord. 3: 23-24.
444. Garcia-Ovejero, D., Arevalo-Martin, A., Petrosino, S., Docagne, F. and others. (2009). The endocannabinoid system is modulated in response to spinal cord injury in rats. Neurobiol.Dis. 33: 57-71.
445. Hama, A. and Sagen, J. (2007). Antinociceptive effect of cannabinoid agonist WIN 55,212-2 in rats with a spinal cord injury. Exp.Neurol. 204: 454-457.
446. Hama, A. and Sagen, J. (2009). Sustained antinociceptive effect of cannabinoid receptor agonist WIN 55,212-2 over time in rat model of neuropathic spinal cord injury pain. J.Rehabil.Res.Dev. 46: 135-143.
447. Malec, J., Harvey, R. F., and Cayner, J. J. (1982). Cannabis effect on spasticity in spinal cord injury. Arch.Phys.Med.Rehabil. 63: 116-118.
448. Maurer, M., Henn, V., Dittrich, A., and Hofmann, A. (1990). Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial. Eur.Arch.Psychiatry Clin.Neurosci. 240: 1-4.
449. Wade, D. T., Robson, P., House, H., Makela, P. and others. (2003). A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin.Rehabil. 17: 21-29.
450. Hagenbach, U., Luz, S., Ghafoor, N., Berger, J. M. and others. (2007). The treatment of spasticity with Delta9tetrahydrocannabinol in persons with spinal cord injury. Spinal Cord. 45: 551-562.
451. Pooyania, S., Ethans, K., Szturm, T., Casey, A. and others. (2010). A randomized, double-blinded, crossover pilot study assessing the effect of nabilone on spasticity in persons with spinal cord injury. Arch.Phys.Med.Rehabil. 91: 703-707.
452. Falenski, K. W., Blair, R. E., Sim-Selley, L. J., Martin, B. R. and others. (2007). Status epilepticus causes a longlasting redistribution of hippocampal cannabinoid type 1 receptor expression and function in the rat pilocarpine model of acquired epilepsy. Neuroscience. 146: 1232-1244.
453. Ludanyi, A., Eross, L., Czirjak, S., Vajda, J. and others. (2008). Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J.Neurosci. 28: 2976-2990.
454. Falenski, K. W., Carter, D. S., Harrison, A. J., Martin, B. R. and others. (2009). Temporal characterization of changes in hippocampal cannabinoid CB(1) receptor expression following pilocarpine-induced status epilepticus. Brain Res. 1262: 64-72.
455. Romigi, A., Bari, M., Placidi, F., Marciani, M. G. and others. (2010). Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy. Epilepsia. 51: 768-772.
456. Wallace, M. J., Martin, B. R., and DeLorenzo, R. J. (2002). Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity. Eur.J.Pharmacol. 452: 295-301.
457. Mechoulam, R. and Lichtman, A. H. (2003). Neuroscience. Stout guards of the central nervous system. Science. 302: 65-67.
458. Wallace, M. J., Blair, R. E., Falenski, K. W., Martin, B. R. and others. (2003). The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J.Pharmacol.Exp.Ther. 307: 129-137.
459. Shafaroodi, H., Samini, M., Moezi, L., Homayoun, H. and others. (2004). The interaction of cannabinoids and opioids on pentylenetetrazole-induced seizure threshold in mice. Neuropharmacology. 47: 390-400.
460. Clement, A. B., Hawkins, E. G., Lichtman, A. H., and Cravatt, B. F. (2003). Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolase. J.Neurosci. 23: 39163923.
461. Alger, B. E. (2002). Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids. Prog.Neurobiol. 68: 247-286.
462. Smith, P. F. (2005). Cannabinoids as potential anti-epileptic drugs. Curr.Opin.Investig.Drugs. 6: 680-685.
463. Hoffman, A. F. and Lupica, C. R. (2000). Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus. J.Neurosci. 20: 2470-2479.
464. Nakatsuka, T., Chen, H. X., Roper, S. N., and Gu, J. G. (2003). Cannabinoid receptor-1 activation suppresses inhibitory synaptic activity in human dentate gyrus. Neuropharmacology. 45: 116-121.
465. Gordon, E. and Devinsky, O. (2001). Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy. Epilepsia. 42: 1266-1272.
466. Lutz, B. (2004). On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. Biochem.Pharmacol. 68: 1691-1698.
467. Gloss, D. and Vickrey, B. (2012). Cannabinoids for epilepsy. Cochrane.Database.Syst.Rev. 6: CD009270-
468. Hama, A. T. and Sagen, J. (2010). Cannabinoid receptor-mediated antinociception with acetaminophen drug combinations in rats with neuropathic spinal cord injury pain. Neuropharmacology. 58: 758-766.
469. Manzanares, J., Julian, M., and Carrascosa, A. (2006). Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr.Neuropharmacol. 4: 239-257.
470. Christie, M. J. and Mallet, C. (2009). Endocannabinoids can open the pain gate. Sci.Signal. 2: pe57.-
471. Ostenfeld, T., Price, J., Albanese, M., Bullman, J. and others. (2011). A Randomized, Controlled Study to Investigate the Analgesic Efficacy of Single Doses of the Cannabinoid Receptor-2 Agonist GW842166, Ibuprofen or Placebo in Patients With Acute Pain Following Third Molar Tooth Extraction. Clin.J.Pain. 27: 668-676.
472. Karst, M., Wippermann, S., and Ahrens, J. (2010). Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs. 70: 2409-2438.
473. Mirchandani, A., Saleeb, M., and Sinatra, R. Acute and Chronic Mechanisms of Pain. Essentials of Pain Management. Vadivelu, N., Urman, R. D., and Hines, R. L. New York: Springer, 2011.
474. Seifert, F. and Maihofner, C. (2011). Functional and structural imaging of pain-induced neuroplasticity. Curr.Opin.Anaesthesiol. 24: 515-523.
475. Zubieta, J. K. and Stohler, C. S. (2009). Neurobiological mechanisms of placebo responses. Ann.N.Y.Acad.Sci. 1156: 198-210.
476. Finniss, D. G., Kaptchuk, T. J., Miller, F., and Benedetti, F. (2010). Biological, clinical, and ethical advances of placebo effects. Lancet. 375: 686-695.
477. Martin, B. R., Compton, D. R., Semus, S. F., Lin, S. and others. (1993). Pharmacological evaluation of iodo and nitro analogs of delta 8-THC and delta 9-THC. Pharmacol.Biochem.Behav. 46: 295-301.
478. Meng, I. D., Manning, B. H., Martin, W. J., and Fields, H. L. (1998). An analgesia circuit activated by cannabinoids. Nature. 395: 381-383.
479. Finn, D. P., Jhaveri, M. D., Beckett, S. R., Roe, C. H. and others. (2003). Effects of direct periaqueductal grey administration of a cannabinoid receptor agonist on nociceptive and aversive responses in rats. Neuropharmacology. 45: 594-604.
480. Azad, S. C., Monory, K., Marsicano, G., Cravatt, B. F. and others. (2004). Circuitry for associative plasticity in the amygdala involves endocannabinoid signaling. J.Neurosci. 24: 9953-9961.
481. Hill, S. Y., Schwin, R., Goodwin, D. W., and Powell, B. J. (1974). Marihuana and pain. J.Pharmacol.Exp.Ther. 188: 415-418.
482. Milstein, S. L., MacCannell, K., Karr, G., and Clark, S. (1975). Marijuana-produced changes in pain tolerance. Experienced and non-experienced subjects. Int.Pharmacopsychiatry. 10: 177-182.
483. Naef, M., Curatolo, M., Petersen-Felix, S., Arendt-Nielsen, L. and others. (2003). The analgesic effect of oral delta9-tetrahydrocannabinol (THC), morphine, and a THC-morphine combination in healthy subjects under experimental pain conditions. Pain. 105: 79-88.
484. Kraft, B., Frickey, N. A., Kaufmann, R. M., Reif, M. and others. (2008). Lack of analgesia by oral standardized cannabis extract on acute inflammatory pain and hyperalgesia in volunteers. Anesthesiology. 109: 101110.
485. Redmond, W. J., Goffaux, P., Potvin, S., and Marchand, S. (2008). Analgesic and antihyperalgesic effects of nabilone on experimental heat pain. Curr.Med.Res.Opin. 24: 1017-1024.
486. Holdcroft, A., Maze, M., Dore, C., Tebbs, S. and others. (2006). A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management. Anesthesiology. 104: 1040-1046.
487. Wu, C. L. and Raja, S. N. (2011). Treatment of acute postoperative pain. Lancet. 377: 2215-2225.
488. Jain, A. K., Ryan, J. R., McMahon, F. G., and Smith, G. (1981). Evaluation of intramuscular levonantradol and placebo in acute postoperative pain. J.Clin.Pharmacol. 21: 320S-326S.
489. Buggy, D. J., Toogood, L., Maric, S., Sharpe, P. and others. (2003). Lack of analgesic efficacy of oral delta-9tetrahydrocannabinol in postoperative pain. Pain. 106: 169-172.
490. Beaulieu, P. (2006). Effects of nabilone, a synthetic cannabinoid, on postoperative pain. Can.J.Anaesth. 53: 769-775.
491. Beaulieu, P. (2007). Cannabinoids for postoperative pain. Anesthesiology. 106: 397-398.
492. Voscopoulos, C. and Lema, M. (2010). When does acute pain become chronic? Br.J.Anaesth. 105 Suppl 1: i69-i85.
493. Fine, P. G., Burton, A. W., and Passik, S. D. (2012). Transformation of acute cancer pain to chronic cancer pain syndromes. J.Support.Oncol. 10: 89-95.
494. Berlach, D. M., Shir, Y., and Ware, M. A. (2006). Experience with the synthetic cannabinoid nabilone in chronic noncancer pain. Pain Med. 7: 25-29.
495. Walker, J. M. and Huang, S. M. (2002). Cannabinoid analgesia. Pharmacol.Ther. 95: 127-135.
496. Rahn, E. J. and Hohmann, A. G. (2009). Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics. 6: 713-737.
497. Costa, B., Trovato, A. E., Comelli, F., Giagnoni, G. and others. (2007). The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur.J.Pharmacol. 556: 75-83.
498. Toth, C. C., Jedrzejewski, N. M., Ellis, C. L., and Frey, W. H. (2010). Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. Mol.Pain. 6: 16-
499. Ashton, J. C. and Milligan, E. D. (2008). Cannabinoids for the treatment of neuropathic pain: clinical evidence. Curr.Opin.Investig.Drugs. 9: 65-75.
500. Grotenhermen, F. (2007). The toxicology of cannabis and cannabis prohibition. Chem.Biodivers. 4: 1744-1769.
501. Wilsey, B., Marcotte, T., Deutsch, R., Gouaux, B. and others. (2012). Low-Dose Vaporized Cannabis Significantly Improves Neuropathic Pain. J.Pain. 14: 136-148.
502. Narang, S., Gibson, D., Wasan, A. D., Ross, E. L. and others. (2008). Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. J.Pain. 9: 254-264.
503. Berman, J. S., Symonds, C., and Birch, R. (2004). Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Pain. 112: 299-306.
504. Rog, D. J., Nurmikko, T. J., Friede, T., and Young, C. A. (2005). Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 65: 812-819.
505. Moulin, D. E., Clark, A. J., Gilron, I., Ware, M. A. and others. (2007). Pharmacological management of chronic neuropathic pain – consensus statement and guidelines from the Canadian Pain Society. Pain Res.Manag. 12: 13-21.
506. Fitzcharles, M. A., Ste-Marie, P. A., Goldenberg, D. L., Pereira, J. X., Abbey, S., Choinier, M., Ko, G., Moulin, D., Panopalis, D., Proulx, J., and Shir, Y. 2012 Canadian Guidelines for the Diagnosis and Management of Fibromyalgia Syndrome. 2012.
507. Noyes, R., Jr., Brunk, S. F., Baram, D. A., and Canter, A. (1975). Analgesic effect of delta-9-tetrahydrocannabinol. J.Clin.Pharmacol. 15: 139-143.
508. Noyes, R., Jr., Brunk, S. F., Avery, D. A., and Canter, A. C. (1975). The analgesic properties of delta-9tetrahydrocannabinol and codeine. Clin.Pharmacol.Ther. 18: 84-89.
509. Johnson, J. R., Lossignol, D., Burnell-Nugent, M., and Fallon, M. T. (2012). An Open-Label Extension Study to Investigate the Long-Term Safety and Tolerability of THC/CBD Oromucosal Spray and Oromucosal THC Spray in Patients With Terminal Cancer-Related Pain Refractory to Strong Opioid Analgesics. J.Pain Symptom.Manage.
510. Bushlin, I., Rozenfeld, R., and Devi, L. A. (2010). Cannabinoid-opioid interactions during neuropathic pain and analgesia. Curr.Opin.Pharmacol. 10: 80-86.
511. Desroches, J. and Beaulieu, P. (2010). Opioids and cannabinoids interactions: involvement in pain management. Curr.Drug Targets. 11: 462-473.
512. Parolaro, D., Rubino, T., Vigano, D., Massi, P. and others. (2010). Cellular mechanisms underlying the interaction between cannabinoid and opioid system. Curr.Drug Targets. 11: 393-405.
513. Rios, C., Gomes, I., and Devi, L. A. (2006). mu opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis. Br.J.Pharmacol. 148: 387-395.
514. Rozenfeld, R., Bushlin, I., Gomes, I., Tzavaras, N. and others. (2012). Receptor heteromerization expands the repertoire of cannabinoid signaling in rodent neurons. PLoS.One. 7: e29239-
515. Welch, S. P. and Stevens, D. L. (1992). Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. J.Pharmacol.Exp.Ther. 262: 10-18.
516. Pugh, G., Jr., Smith, P. B., Dombrowski, D. S., and Welch, S. P. (1996). The role of endogenous opioids in enhancing the antinociception produced by the combination of delta 9-tetrahydrocannabinol and morphine in the spinal cord. J.Pharmacol.Exp.Ther. 279: 608-616.
517. Smith, F. L., Cichewicz, D., Martin, Z. L., and Welch, S. P. (1998). The enhancement of morphine antinociception in mice by delta9-tetrahydrocannabinol. Pharmacol.Biochem.Behav. 60: 559-566.
518. Cichewicz, D. L. and McCarthy, E. A. (2003). Antinociceptive synergy between delta(9)-tetrahydrocannabinol and opioids after oral administration. J.Pharmacol.Exp.Ther. 304: 1010-1015.
519. Cichewicz, D. L. (2004). Synergistic interactions between cannabinoid and opioid analgesics. Life Sci. 74: 13171324.
520. Smith, P. A., Selley, D. E., Sim-Selley, L. J., and Welch, S. P. (2007). Low dose combination of morphine and delta9-tetrahydrocannabinol circumvents antinociceptive tolerance and apparent desensitization of receptors. Eur.J.Pharmacol. 571: 129-137.
521. Roberts, J. D., Gennings, C., and Shih, M. (2006). Synergistic affective analgesic interaction between delta-9tetrahydrocannabinol and morphine. Eur.J.Pharmacol. 530: 54-58.
522. Greco, R., Gasperi, V., Maccarrone, M., and Tassorelli, C. (2010). The endocannabinoid system and migraine. Exp.Neurol. 224: 85-91.
523. Napchan, U., Buse, D. C., and Loder, E. W. (2011). The use of marijuana or synthetic cannabinoids for the treatment of headache. Headache. 51: 502-505.
524. McGeeney, B. E. (2012). Hallucinogens and cannabinoids for headache. Headache. 52 Suppl 2: 94-97.
525. Russo, E. B. (2004). Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro.Endocrinol.Lett. 25: 31-39.
526. Sarchielli, P., Pini, L. A., Coppola, F., Rossi, C. and others. (2007). Endocannabinoids in chronic migraine: CSF findings suggest a system failure. Neuropsychopharmacology. 32: 1384-1390.
527. Villalon, C. M. and Olesen, J. (2009). The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs. Pharmacol.Ther. 124: 309-323.
528. Cupini, L. M., Costa, C., Sarchielli, P., Bari, M. and others. (2008). Degradation of endocannabinoids in chronic migraine and medication overuse headache. Neurobiol.Dis. 30: 186-189.
529. Evans, R. W. and Ramadan, N. M. (2004). Are cannabis-based chemicals helpful in headache? Headache. 44: 726727.
530. Robbins, M. S., Tarshish, S., Solomon, S., and Grosberg, B. M. (2009). Cluster attacks responsive to recreational cannabis and dronabinol. Headache. 49: 914-916.
531. Leroux, E., Taifas, I., Valade, D., Donnet, A. and others. (2012). Use of cannabis among 139 cluster headache sufferers. Cephalalgia. 33: 208-213.
532. Ducros, A., Boukobza, M., Porcher, R., Sarov, M. and others. (2007). The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients. Brain. 130: 3091-3101.
533. Levin, K. H., Copersino, M. L., Heishman, S. J., Liu, F. and others. (2010). Cannabis withdrawal symptoms in nontreatment-seeking adult cannabis smokers. Drug Alcohol Depend. 111: 120-127.
534. Dunkley, L and Tattersall, R. (2012). Osteoarthritis and the inflammatory arthritides. Surgery. 30: 67-71.
535. Sagar, D. R., Staniaszek, L. E., Okine, B. N., Woodhams, S. and others. (2010). Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain. Arthritis Rheum. 62: 3666-3676.
536. Schuelert, N. and McDougall, J. J. (2008). Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum. 58: 145-153.
537. Schuelert, N., Johnson, M. P., Oskins, J. L., Jassal, K. and others. (2011). Local application of the endocannabinoid hydrolysis inhibitor URB597 reduces nociception in spontaneous and chemically induced models of osteoarthritis. Pain. 152: 975-981.
538. Richards, B. L., Whittle, S. L., and Buchbinder, R. (2012). Neuromodulators for pain management in rheumatoid arthritis. Cochrane.Database.Syst.Rev. 1: CD008921-
539. McInnes, I. B. and Schett, G. (2011). The pathogenesis of rheumatoid arthritis. N.Engl.J.Med. 365: 2205-2219.
540. Smith, H. S., Bracken, D., and Smith, J. M. (2011). Pharmacotherapy for fibromyalgia. Front Pharmacol. 2: 17-
541. Julien, N., Goffaux, P., Arsenault, P., and Marchand, S. (2005). Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain. 114: 295-302.
542. Clauw, D. J., Arnold, L. M., and McCarberg, B. H. (2011). The science of fibromyalgia. Mayo Clin.Proc. 86: 907911.
543. Normand, E., Potvin, S., Gaumond, I., Cloutier, G. and others. (2011). Pain inhibition is deficient in chronic widespread pain but normal in major depressive disorder. J.Clin.Psychiatry. 72: 219-224.
544. Becker, S. and Schweinhardt, P. (2012). Dysfunctional neurotransmitter systems in fibromyalgia, their role in central stress circuitry and pharmacological actions on these systems. Pain Res.Treat. 2012: 741746-
545. de Souza, J. B., Potvin, S., Goffaux, P., Charest, J. and others. (2009). The deficit of pain inhibition in fibromyalgia is more pronounced in patients with comorbid depressive symptoms. Clin.J.Pain. 25: 123-127.
546. Wolfe, F., Clauw, D. J., Fitzcharles, M. A., Goldenberg, D. L. and others. (2010). The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res.(Hoboken.). 62: 600-610.
547. Idris, A. I., Sophocleous, A., Landao-Bassonga, E., Canals, M. and others. (2009). Cannabinoid receptor type 1 protects against age-related osteoporosis by regulating osteoblast and adipocyte differentiation in marrow stromal cells. Cell Metab. 10: 139-147.
548. Bab, I., Smoum, R., Bradshaw, H., and Mechoulam, R. (2011). Skeletal lipidomics: regulation of bone metabolism by fatty acid amide family. Br.J.Pharmacol. 163: 1441-1446.
549. Idris, A. I., van ‘t Hof, R. J., Greig, I. R., Ridge, S. A. and others. (2005). Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat.Med. 11: 774-779.
550. Whyte, L. S., Ford, L., Ridge, S. A., Cameron, G. A. and others. (2012). Cannabinoids and bone: endocannabinoids modulate human osteoclast function in vitro. Br.J.Pharmacol. 165: 2584-2597.
551. Tam, J., Ofek, O., Fride, E., Ledent, C. and others. (2006). Involvement of neuronal cannabinoid receptor CB1 in regulation of bone mass and bone remodeling. Mol.Pharmacol. 70: 786-792.
552. Tam, J., Trembovler, V., Di, Marzo, V, Petrosino, S. and others. (2008). The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling. FASEB J. 22: 285-294.
553. Rossi, F., Siniscalco, D., Luongo, L., De, Petrocellis L. and others. (2009). The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption. Bone. 44: 476-484.
554. Ofek, O., Karsak, M., Leclerc, N., Fogel, M. and others. (2006). Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc.Natl.Acad.Sci.U.S.A. 103: 696-701.
555. Sophocleous, A., Landao-Bassonga, E., van’t Hof, R. J., Idris, A. I. and others. (2011). The type 2 cannabinoid receptor regulates bone mass and ovariectomy-induced bone loss by affecting osteoblast differentiation and bone formation. Endocrinology. 152: 2141-2149.
556. Idris, A. I., Sophocleous, A., Landao-Bassonga, E., van’t Hof, R. J. and others. (2008). Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss by the type 2 cannabinoid receptor. Endocrinology. 149: 5619-5626.
557. Karsak, M., Cohen-Solal, M., Freudenberg, J., Ostertag, A. and others. (2005). Cannabinoid receptor type 2 gene is associated with human osteoporosis. Hum.Mol.Genet. 14: 3389-3396.
558. Karsak, M., Malkin, I., Toliat, M. R., Kubisch, C. and others. (2009). The cannabinoid receptor type 2 (CNR2) gene is associated with hand bone strength phenotypes in an ethnically homogeneous family sample. Hum.Genet. 126: 629-636.
559. Huang, Q. Y., Li, G. H., and Kung, A. W. (2009). Multiple osteoporosis susceptibility genes on chromosome 1p36 in Chinese. Bone. 44: 984-988.
560. Fernandez-Ruiz, J. (2009). The endocannabinoid system as a target for the treatment of motor dysfunction. Br.J.Pharmacol. 156: 1029-1040.
561. Glass, M., Dragunow, M., and Faull, R. L. (2000). The pattern of neurodegeneration in Huntington’s disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington’s disease. Neuroscience. 97: 505-519.
562. Romero, J., Berrendero, F., Perez-Rosado, A., Manzanares, J. and others. (2000). Unilateral 6-hydroxydopamine lesions of nigrostriatal dopaminergic neurons increased CB1 receptor mRNA levels in the caudateputamen. Life Sci. 66: 485-494.
563. Lastres-Becker, I., Fezza, F., Cebeira, M., Bisogno, T. and others. (2001). Changes in endocannabinoid transmission in the basal ganglia in a rat model of Huntington’s disease. Neuroreport. 12: 2125-2129.
564. Garcia-Arencibia, M., Garcia, C., and Fernandez-Ruiz, J. (2009). Cannabinoids and Parkinson’s disease. CNS.Neurol.Disord.Drug Targets. 8: 432-439.
565. Richter, A. and Loscher, W. (1994). (+)-WIN 55,212-2, a novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters. Eur.J.Pharmacol. 264: 371-377.
566. Richter, A. and Loscher, W. (2002). Effects of pharmacological manipulations of cannabinoid receptors on severity of dystonia in a genetic model of paroxysmal dyskinesia. Eur.J.Pharmacol. 454: 145-151.
567. Madsen, M. V., Peacock, L. P., Werge, T., Andersen, M. B. and others. (2011). Effects of cannabinoid CB(1) receptor agonism and antagonism on SKF81297-induced dyskinesia and haloperidol-induced dystonia in Cebus apella monkeys. Neuropharmacology. 60: 418-422.
568. Uribe Roca, M. C., Micheli, F., and Viotti, R. (2005). Cannabis sativa and dystonia secondary to Wilson’s disease. Mov Disord. 20: 113-115.
569. Jabusch, H. C., Schneider, U., and Altenmuller, E. (2004). Delta9-tetrahydrocannabinol improves motor control in a patient with musician’s dystonia. Mov Disord. 19: 990-991.
570. Consroe, P., Sandyk, R., and Snider, S. R. (1986). Open label evaluation of cannabidiol in dystonic movement disorders. Int.J.Neurosci. 30: 277-282.
571. Fox, S. H., Kellett, M., Moore, A. P., Crossman, A. R. and others. (2002). Randomised, double-blind, placebocontrolled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Mov Disord. 17: 145-149.
572. Denovan-Wright, E. M. and Robertson, H. A. (2000). Cannabinoid receptor messenger RNA levels decrease in a subset of neurons of the lateral striatum, cortex and hippocampus of transgenic Huntington’s disease mice. Neuroscience. 98: 705-713.
573. Lastres-Becker, I., Gomez, M., de, Miguel R., Ramos, J. A. and others. (2002). Loss of cannabinoid CB(1) receptors in the basal ganglia in the late akinetic phase of rats with experimental Huntington’s disease. Neurotox.Res. 4: 601-608.
574. Naver, B., Stub, C., Moller, M., Fenger, K. and others. (2003). Molecular and behavioral analysis of the R6/1 Huntington’s disease transgenic mouse. Neuroscience. 122: 1049-1057.
575. McCaw, E. A., Hu, H., Gomez, G. T., Hebb, A. L. and others. (2004). Structure, expression and regulation of the cannabinoid receptor gene (CB1) in Huntington’s disease transgenic mice. Eur.J.Biochem. 271: 4909-4920.
576. Centonze, D., Rossi, S., Prosperetti, C., Tscherter, A. and others. (2005). Abnormal sensitivity to cannabinoid receptor stimulation might contribute to altered gamma-aminobutyric acid transmission in the striatum of R6/2 Huntington’s disease mice. Biol.Psychiatry. 57: 1583-1589.
577. Pazos, M. R., Sagredo, O., and Fernandez-Ruiz, J. (2008). The endocannabinoid system in Huntington’s disease. Curr.Pharm.Des. 14: 2317-2325.
578. Dowie, M. J., Bradshaw, H. B., Howard, M. L., Nicholson, L. F. and others. (2009). Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington’s disease. Neuroscience. 163: 456-465.
579. Blazquez, C., Chiarlone, A., Sagredo, O., Aguado, T. and others. (2011). Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington’s disease. Brain. 134: 119-136.
580. Casteels, C., Vandeputte, C., Rangarajan, J. R., Dresselaers, T. and others. (2011). Metabolic and type 1 cannabinoid receptor imaging of a transgenic rat model in the early phase of Huntington disease. Exp.Neurol. 229: 440449.
581. Mievis, S., Blum, D., and Ledent, C. (2011). Worsening of Huntington disease phenotype in CB1 receptor knockout mice. Neurobiol.Dis. 42: 524-529.
582. Van Laere K., Casteels, C., Dhollander, I., Goffin, K. and others. (2010). Widespread decrease of type 1 cannabinoid receptor availability in Huntington disease in vivo. J.Nucl.Med. 51: 1413-1417.
583. Palazuelos, J., Aguado, T., Pazos, M. R., Julien, B. and others. (2009). Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain. 132: 3152-3164.
584. Dowie, M. J., Howard, M. L., Nicholson, L. F., Faull, R. L. and others. (2010). Behavioural and molecular consequences of chronic cannabinoid treatment in Huntington’s disease transgenic mice. Neuroscience. 170: 324-336.
585. Consroe, P., Laguna, J., Allender, J., Snider, S. and others. (1991). Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol.Biochem.Behav. 40: 701-708.
586. Curtis, A., Mitchell, I., Patel, S., Ives, N. and others. (2009). A pilot study using nabilone for symptomatic treatment in Huntington’s disease. Mov Disord. 24: 2254-2259.
587. Muller-Vahl, K. R., Schneider, U., and Emrich, H. M. (1999). Nabilone increases choreatic movements in Huntington’s disease. Mov Disord. 14: 1038-1040.
588. Curtis, A. and Rickards, H. (2006). Nabilone could treat chorea and irritability in Huntington’s disease. J.Neuropsychiatry Clin.Neurosci. 18: 553-554.
589. Pisani, V., Moschella, V., Bari, M., Fezza, F. and others. (2010). Dynamic changes of anandamide in the cerebrospinal fluid of Parkinson’s disease patients. Mov Disord. 25: 920-924.
590. Pisani, A., Fezza, F., Galati, S., Battista, N. and others. (2005). High endogenous cannabinoid levels in the cerebrospinal fluid of untreated Parkinson’s disease patients. Ann.Neurol. 57: 777-779.
591. Garcia-Arencibia, M., Garcia, C., Kurz, A., Rodriguez-Navarro, J. A. and others. (2009). Cannabinoid CB1 receptors are early downregulated followed by a further upregulation in the basal ganglia of mice with deletion of specific park genes. J.Neural Transm.Suppl. 269-275.
592. Papa, S. M. (2008). The cannabinoid system in Parkinson’s disease: multiple targets to motor effects. Exp.Neurol. 211: 334-338.
593. Garcia, C., Palomo, C., Garcia-Arencibia, M., Ramos, J. A. and others. (2011). Symptom-relieving and neuroprotective effects of the phytocannabinoid D(9) -THCV in animal models of Parkinson’s disease. Br.J.Pharmacol. 163: 1495-1506.
594. Frankel, J. P., Hughes, A., Lees, A. J., and Stern, G. M. (1990). Marijuana for parkinsonian tremor. J.Neurol.Neurosurg.Psychiatry. 53: 436.-
595. Sieradzan, K. A., Fox, S. H., Hill, M., Dick, J. P. and others. (2001). Cannabinoids reduce levodopa-induced dyskinesia in Parkinson’s disease: a pilot study. Neurology. 57: 2108-2111.
596. Carroll, C. B., Bain, P. G., Teare, L., Liu, X. and others. (2004). Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Neurology. 63: 1245-1250.
597. Sandyk, R. and Awerbuch, G. (1988). Marijuana and Tourette’s syndrome. J.Clin.Psychopharmacol. 8: 444-445.
598. Hemming, M. and Yellowlees, P. M. (1993). Effective treatment of Tourette’s syndrome with marijuana. Journal of Psychopharmacology. 7: 389-391.
599. Muller-Vahl, K. R., Koblenz, A., Jobges, M., Kolbe, H. and others. (2001). Influence of treatment of Tourette syndrome with delta9-tetrahydrocannabinol (delta9-THC) on neuropsychological performance. Pharmacopsychiatry. 34: 19-24.
600. Muller-Vahl, K. R., Schneider, U., Prevedel, H., Theloe, K. and others. (2003). Delta 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6-week randomized trial. J.Clin.Psychiatry. 64: 459-465.
601. Curtis, A., Clarke, C. E., and Rickards, H. E. (2009). Cannabinoids for Tourette’s Syndrome. Cochrane.Database.Syst.Rev. CD006565.-
602. Cheung, W., Guo, L., and Cordeiro, M. F. (2008). Neuroprotection in glaucoma: drug-based approaches. Optom.Vis.Sci. 85: 406-416.
603. Jarvinen, T., Pate, D. W., and Laine, K. (2002). Cannabinoids in the treatment of glaucoma. Pharmacol.Ther. 95: 203-220.
604. Jampel, H. (2010). American glaucoma society position statement: marijuana and the treatment of glaucoma. J.Glaucoma. 19: 75-76.
605. Chen, J., Matias, I., Dinh, T., Lu, T. and others. (2005). Finding of endocannabinoids in human eye tissues: implications for glaucoma. Biochem.Biophys.Res.Commun. 330: 1062-1067.
606. Porcella, A., Casellas, P., Gessa, G. L., and Pani, L. (1998). Cannabinoid receptor CB1 mRNA is highly expressed in the rat ciliary body: implications for the antiglaucoma properties of marihuana. Brain Res.Mol.Brain Res. 58: 240-245.
607. Straiker, A. J., Maguire, G., Mackie, K., and Lindsey, J. (1999). Localization of cannabinoid CB1 receptors in the human anterior eye and retina. Invest Ophthalmol.Vis.Sci. 40: 2442-2448.
608. Porcella, A., Maxia, C., Gessa, G. L., and Pani, L. (2000). The human eye expresses high levels of CB1 cannabinoid receptor mRNA and protein. Eur.J.Neurosci. 12: 1123-1127.
609. Song, Z. H. and Slowey, C. A. (2000). Involvement of cannabinoid receptors in the intraocular pressure-lowering effects of WIN55212-2. J.Pharmacol.Exp.Ther. 292: 136-139.
610. Porcella, A., Maxia, C., Gessa, G. L., and Pani, L. (2001). The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies. Eur.J.Neurosci. 13: 409-412.
611. Flach, A. J. (2002). Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Trans.Am.Ophthalmol.Soc. 100: 215-222.
612. Yoles, E., Belkin, M., and Schwartz, M. (1996). HU-211, a nonpsychotropic cannabinoid, produces short- and longterm neuroprotection after optic nerve axotomy. J.Neurotrauma. 13: 49-57.
613. Shen, M. and Thayer, S. A. (1998). Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity. Mol.Pharmacol. 54: 459-462.
614. Levin, L. A. (1999). Direct and indirect approaches to neuroprotective therapy of glaucomatous optic neuropathy. Surv.Ophthalmol. 43 Suppl 1: S98-101.
615. Jin, K. L., Mao, X. O., Goldsmith, P. C., and Greenberg, D. A. (2000). CB1 cannabinoid receptor induction in experimental stroke. Ann.Neurol. 48: 257-261.
616. Panikashvili, D., Simeonidou, C., Ben-Shabat, S., Hanus, L. and others. (2001). An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature. 413: 527-531.
617. Marsicano, G., Moosmann, B., Hermann, H., Lutz, B. and others. (2002). Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1. J.Neurochem. 80: 448-456.
618. Mechoulam, R., Panikashvili, D., and Shohami, E. (2002). Cannabinoids and brain injury: therapeutic implications. Trends Mol.Med. 8: 58-61.
619. Braida, D., Pegorini, S., Arcidiacono, M. V., Consalez, G. G. and others. (2003). Post-ischemic treatment with cannabidiol prevents electroencephalographic flattening, hyperlocomotion and neuronal injury in gerbils. Neurosci.Lett. 346: 61-64.
620. El-Remessy, A. B., Al-Shabrawey, M., Khalifa, Y., Tsai, N. T. and others. (2006). Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes. Am.J.Pathol. 168: 235-244.
621. Gilbert, G. L., Kim, H. J., Waataja, J. J., and Thayer, S. A. (2007). Delta9-tetrahydrocannabinol protects hippocampal neurons from excitotoxicity. Brain Res. 1128: 61-69.
622. Wan, M. J., Daniel, S., Kassam, F., Mutti, G. and others. (2012). Survey of complementary and alternative medicine use in glaucoma patients. J.Glaucoma. 21: 79-82.
623. Hepler, R. S. and Frank, I. R. (1971). Marihuana smoking and intraocular pressure. JAMA. 217: 1392.-
624. Merritt, J. C., Crawford, W. J., Alexander, P. C., Anduze, A. L. and others. (1980). Effect of marihuana on intraocular and blood pressure in glaucoma. Ophthalmology. 87: 222-228.
625. Zhan, G. L., Camras, C. B., Palmberg, P. F., and Toris, C. B. (2005). Effects of marijuana on aqueous humor dynamics in a glaucoma patient. J.Glaucoma. 14: 175-177.
626. Abboud, R. T. and Sanders, H. D. (1976). Effect of oral administration of delta-tetrahydrocannabinol on airway mechanics in normal and asthmatic subjects. Chest. 70: 480-485.
627. Calignano, A., Katona, I., Desarnaud, F., Giuffrida, A. and others. (2000). Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature. 408: 96-101.
628. Jan, T. R., Farraj, A. K., Harkema, J. R., and Kaminski, N. E. (2003). Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatment in A/J mice. Toxicol.Appl.Pharmacol. 188: 24-35.
629. Giannini, L., Nistri, S., Mastroianni, R., Cinci, L. and others. (2008). Activation of cannabinoid receptors prevents antigen-induced asthma-like reaction in guinea pigs. J.Cell Mol.Med. 12: 2381-2394.
630. Fukuda, H., Abe, T., and Yoshihara, S. (2010). The cannabinoid receptor agonist WIN 55,212-2 inhibits antigeninduced plasma extravasation in guinea pig airways. Int.Arch.Allergy Immunol. 152: 295-300.
631. Vachon, L., FitzGerald, M. X., Solliday, N. H., Gould, I. A. and others. (1973). Single-dose effects of marihuana smoke. Bronchial dynamics and respiratory-center sensitivity in normal subjects. N.Engl.J.Med. 288: 985989.
632. Tashkin, D. P., Shapiro, B. J., and Frank, I. M. (1973). Acute pulmonary physiologic effects of smoked marijuana and oral 9 -tetrahydrocannabinol in healthy young men. N.Engl.J.Med. 289: 336-341.
633. Tashkin, D. P. (2001). Airway effects of marijuana, cocaine, and other inhaled illicit agents. Curr.Opin.Pulm.Med. 7: 43-61.
634. Tashkin, D. P., Shapiro, B. J., and Frank, I. M. (1974). Acute effects of smoked marijuana and oral delta9tetrahydrocannabinol on specific airway conductance in asthmatic subjects. Am.Rev.Respir.Dis. 109: 420428.
635. Tashkin, D. P., Shapiro, B. J., Lee, Y. E., and Harper, C. E. (1975). Effects of smoked marijuana in experimentally induced asthma. Am.Rev.Respir.Dis. 112: 377-386.
636. Gong, H., Jr., Tashkin, D. P., Simmons, M. S., Calvarese, B. and others. (1984). Acute and subacute bronchial effects of oral cannabinoids. Clin.Pharmacol.Ther. 35: 26-32.
637. Williams, S. J., Hartley, J. P., and Graham, J. D. (1976). Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. Thorax. 31: 720-723.
638. Hartley, J. P., Nogrady, S. G., and Seaton, A. (1978). Bronchodilator effect of delta1-tetrahydrocannabinol. Br.J.Clin.Pharmacol. 5: 523-525.
639. Tashkin, D. P., Shapiro, B. J., Lee, Y. E., and Harper, C. E. (1976). Subacute effects of heavy marihuana smoking on pulmonary function in healthy men. N.Engl.J.Med. 294: 125-129.
640. Davies, B. H., Radcliffe, S., Seaton, A., and Graham, J. D. (1975). A trial of oral delta-1-(trans)tetrahydrocannabinol in reversible airways obstruction. Thorax. 30: 80-85.
641. Gong, H., Jr., Tashkin, D. P., and Calvarese, B. (1983). Comparison of bronchial effects of nabilone and terbutaline in healthy and asthmatic subjects. J.Clin.Pharmacol. 23: 127-133.
642. Pacher, P., Batkai, S., and Kunos, G. (2005). Cardiovascular pharmacology of cannabinoids. Handb.Exp.Pharmacol. 599-625.
643. Crawford, W. J. and Merritt, J. C. (1979). Effects of tetrahydrocannabinol on arterial and intraocular hypertension. Int.J.Clin.Pharmacol.Biopharm. 17: 191-196.
644. Denson, T. F. and Earleywine, M. (2006). Decreased depression in marijuana users. Addict.Behav. 31: 738-742.
645. Witkin, J. M., Tzavara, E. T., and Nomikos, G. G. (2005). A role for cannabinoid CB1 receptors in mood and anxiety disorders. Behav.Pharmacol. 16: 315-331.
646. Moreira, F. A. and Wotjak, C. T. (2010). Cannabinoids and anxiety. Curr.Top.Behav.Neurosci. 2: 429-450.
647. Bambico, F. R., Katz, N., Debonnel, G., and Gobbi, G. (2007). Cannabinoids elicit antidepressant-like behavior and activate serotonergic neurons through the medial prefrontal cortex. J.Neurosci. 27: 11700-11711.
648. Bambico, F. R. and Gobbi, G. (2008). The cannabinoid CB1 receptor and the endocannabinoid anandamide: possible antidepressant targets. Expert.Opin.Ther.Targets. 12: 1347-1366.
649. Hill, M. N. and Gorzalka, B. B. (2005). Pharmacological enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the rat forced swim test. Eur.Neuropsychopharmacol. 15: 593-599.
650. Christensen, R., Kristensen, P. K., Bartels, E. M., Bliddal, H. and others. (2007). Efficacy and safety of the weightloss drug rimonabant: a meta-analysis of randomised trials. Lancet. 370: 1706-1713.
651. Gorzalka, B. B. and Hill, M. N. (2010). Putative role of endocannabinoid signaling in the etiology of depression and actions of antidepressants. Prog.Neuropsychopharmacol.Biol.Psychiatry. 35: 1575-1585.
652. Hill, M. N., Miller, G. E., Carrier, E. J., Gorzalka, B. B. and others. (2009). Circulating endocannabinoids and Nacyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology. 34: 1257-1262.
653. Woolridge, E., Barton, S., Samuel, J., Osorio, J. and others. (2005). Cannabis use in HIV for pain and other medical symptoms. J.Pain Symptom.Manage. 29: 358-367.
654. Page, S. A. and Verhoef, M. J. (2006). Medicinal marijuana use: experiences of people with multiple sclerosis. Can.Fam.Physician. 52: 64-65.
655. Mitchell, P. B. and Morris, M. J. (2007). Depression and anxiety with rimonabant. Lancet. 370: 1671-1672.
656. Morgan, C. J., Schafer, G., Freeman, T. P., and Curran, H. V. (2010). Impact of cannabidiol on the acute memory and psychotomimetic effects of smoked cannabis: naturalistic study: naturalistic study [corrected]. Br.J.Psychiatry. 197: 285-290.
657. Guimaraes, F. S., de Aguiar, J. C., Mechoulam, R., and Breuer, A. (1994). Anxiolytic effect of cannabidiol derivatives in the elevated plus-maze. Gen.Pharmacol. 25: 161-164.
658. Crippa, J. A., Zuardi, A. W., Garrido, G. E., Wichert-Ana, L. and others. (2004). Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology. 29: 417-426.
659. Bergamaschi, M. M., Queiroz, R. H., Chagas, M. H., de Oliveira, D. C. and others. (2011). Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naive social phobia patients. Neuropsychopharmacology. 36: 1219-1226.
660. Resstel, L. B., Tavares, R. F., Lisboa, S. F., Joca, S. R. and others. (2009). 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br.J.Pharmacol. 156: 181-188.
661. Gomes, F. V., Resstel, L. B., and Guimaraes, F. S. (2011). The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Psychopharmacology (Berl). 213: 465-473.
662. Koethe, D., Schreiber, D., Giuffrida, A., Mauss, C. and others. (2009). Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid. J.Neural Transm. 116: 301-305.
663. Herrera-Solis, A., Vasquez, K. G., and Prospero-Garcia, O. (2010). Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats. Pharmacol.Biochem.Behav. 95: 106-112.
664. Bolla, K. I., Lesage, S. R., Gamaldo, C. E., Neubauer, D. N. and others. (2008). Sleep disturbance in heavy marijuana users. Sleep. 31: 901-908.
665. Bolla, K. I., Lesage, S. R., Gamaldo, C. E., Neubauer, D. N. and others. (2010). Polysomnogram changes in marijuana users who report sleep disturbances during prior abstinence. Sleep Med. 11: 882-889.
666. Lutz, B. (2007). The endocannabinoid system and extinction learning. Mol.Neurobiol. 36: 92-101.
667. Pamplona, F. A., Prediger, R. D., Pandolfo, P., and Takahashi, R. N. (2006). The cannabinoid receptor agonist WIN 55,212-2 facilitates the extinction of contextual fear memory and spatial memory in rats. Psychopharmacology (Berl). 188: 641-649.
668. Marsicano, G., Wotjak, C. T., Azad, S. C., Bisogno, T. and others. (2002). The endogenous cannabinoid system controls extinction of aversive memories. Nature. 418: 530-534.
669. Varvel, S. A. and Lichtman, A. H. (2002). Evaluation of CB1 receptor knockout mice in the Morris water maze. J.Pharmacol.Exp.Ther. 301: 915-924.
670. Chhatwal, J. P., Davis, M., Maguschak, K. A., and Ressler, K. J. (2005). Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Neuropsychopharmacology. 30: 516-524.
671. Pava, M. J. and Woodward, J. J. (2012). A review of the interactions between alcohol and the endocannabinoid system: implications for alcohol dependence and future directions for research. Alcohol. 46: 185-204.
672. Deikel, S. M. and Carder, B. (1976). Attentuation of precipitated abstinence in methadone-dependent rats by delta9THC. Psychopharmacol.Commun. 2: 61-65.
673. Vela, G., Fuentes, J. A., Bonnin, A., Fernandez-Ruiz, J. and others. (1995). Perinatal exposure to delta 9tetrahydrocannabinol (delta 9-THC) leads to changes in opioid-related behavioral patterns in rats. Brain Res. 680: 142-147.
674. Yamaguchi, T., Hagiwara, Y., Tanaka, H., Sugiura, T. and others. (2001). Endogenous cannabinoid, 2arachidonoylglycerol, attenuates naloxone-precipitated withdrawal signs in morphine-dependent mice. Brain Res. 909: 121-126.
675. Reiman, A. (2009). Cannabis as a substitute for alcohol and other drugs. Harm.Reduct.J. 6: 35-39.
676. Fernandez-Espejo, E., Viveros, M. P., Nunez, L., Ellenbroek, B. A. and others. (2009). Role of cannabis and endocannabinoids in the genesis of schizophrenia. Psychopharmacology (Berl). 206: 531-549.
677. Koethe, D., Giuffrida, A., Schreiber, D., Hellmich, M. and others. (2009). Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. Br.J.Psychiatry. 194: 371-372.
678. Leweke, F. M., Giuffrida, A., Wurster, U., Emrich, H. M. and others. (1999). Elevated endogenous cannabinoids in schizophrenia. Neuroreport. 10: 1665-1669.
679. De Marchi, N., De Petrocellis, L., Orlando, P., Daniele, F. and others. (2003). Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids Health Dis. 2: 5.-
680. Rodriguez de Fonseca, F., Gorriti, M. A., Bilbao, A., Escuredo, L. and others. (2001). Role of the endogenous cannabinoid system as a modulator of dopamine transmission: implications for Parkinson’s disease and schizophrenia. Neurotox.Res. 3: 23-35.
681. McCreadie, R. G. (2002). Use of drugs, alcohol and tobacco by people with schizophrenia: case-control study. Br.J.Psychiatry. 181: 321-325.
682. Gregg, L., Barrowclough, C., and Haddock, G. (2007). Reasons for increased substance use in psychosis. Clin.Psychol.Rev. 27: 494-510.
683. Khantzian, E. J. (1985). The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am.J.Psychiatry. 142: 1259-1264.
684. Lembke, A. (2012). Time to abandon the self-medication hypothesis in patients with psychiatric disorders. Am.J.Drug Alcohol Abuse. 38: 524-529.
685. Chambers, R. A., Krystal, J. H., and Self, D. W. (2001). A neurobiological basis for substance abuse comorbidity in schizophrenia. Biol.Psychiatry. 50: 71-83.
686. Caspi, A., Moffitt, T. E., Cannon, M., McClay, J. and others. (2005). Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol.Psychiatry. 57: 1117-1127.
687. Henquet, C., Rosa, A., Krabbendam, L., Papiol, S. and others. (2006). An experimental study of catechol-omethyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology. 31: 2748-2757.
688. Henquet, C., Rosa, A., Delespaul, P., Papiol, S. and others. (2009). COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of ‘switching on’ hallucinations in the flow of daily life. Acta Psychiatr.Scand. 119: 156-160.
689. Pelayo-Teran, J. M., Perez-Iglesias, R., Mata, I., Carrasco-Marin, E. and others. (2010). Catechol-OMethyltransferase (COMT) Val158Met variations and cannabis use in first-episode non-affective psychosis: clinical-onset implications. Psychiatry Res. 179: 291-296.
690. Estrada, G., Fatjo-Vilas, M., Munoz, M. J., Pulido, G. and others. (2011). Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism. Acta Psychiatr.Scand. 123: 485-492.
691. van Winkel, R., van Beveren, N. J., and Simons, C. (2011). AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder. Neuropsychopharmacology. 36: 2529-2537.
692. van Winkel, R. (2011). Family-based analysis of genetic variation underlying psychosis-inducing effects of cannabis: sibling analysis and proband follow-up. Arch.Gen.Psychiatry. 68: 148-157.
693. Di Forti, M., Iyegbe, C., Sallis, H., Kolliakou, A. and others. (2012). Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users. Biol.Psychiatry. 72: 811-816.
694. Leweke, F. M., Schneider, U., Radwan, M., Schmidt, E. and others. (2000). Different effects of nabilone and cannabidiol on binocular depth inversion in Man. Pharmacol.Biochem.Behav. 66: 175-181.
695. Musty, R. Cannabinoids and anxiety. Cannabinoids as Therapeutics. Mechoulam, R. Basel: Birkhaüser, 2005.
696. Zuardi, A. W., Rodrigues, J. A., and Cunha, J. M. (1991). Effects of cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology (Berl). 104: 260-264.
697. Moreira, F. A. and Guimaraes, F. S. (2005). Cannabidiol inhibits the hyperlocomotion induced by psychotomimetic drugs in mice. Eur.J.Pharmacol. 512: 199-205.
698. Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D. and others. (2012). Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl.Psychiatry. 2: e94-
699. Zuardi, A. W. (2008). Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev.Bras.Psiquiatr. 30: 271-280.
700. Benito, C., Nunez, E., Pazos, M. R., Tolon, R. M. and others. (2007). The endocannabinoid system and Alzheimer’s disease. Mol.Neurobiol. 36: 75-81.
701. Koppel, J. and Davies, P. (2008). Targeting the endocannabinoid system in Alzheimer’s disease. J.Alzheimers.Dis. 15: 495-504.
702. van der Stelt, M., Mazzola, C., Esposito, G., Matias, I. and others. (2006). Endocannabinoids and beta-amyloidinduced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels. Cell Mol.Life Sci. 63: 1410-1424.
703. Jung, K. M., Astarita, G., Yasar, S., Vasilevko, V. and others. (2011). An amyloid beta(42)-dependent deficit in anandamide mobilization is associated with cognitive dysfunction in Alzheimer’s disease. Neurobiol.Aging. 33: 1522-1532.
704. Noonan, J., Tanveer, R., Klompas, A., Gowran, A. and others. (2010). Endocannabinoids prevent beta-amyloidmediated lysosomal destabilization in cultured neurons. J.Biol.Chem. 285: 38543-38554.
705. Eubanks, L. M., Rogers, C. J., Beuscher, A. E., Koob, G. F. and others. (2006). A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Mol.Pharm. 3: 773-777.
706. Iuvone, T., Esposito, G., Esposito, R., Santamaria, R. and others. (2004). Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells. J.Neurochem. 89: 134-141.
707. Esposito, G., De, Filippis D., Carnuccio, R., Izzo, A. A. and others. (2006). The marijuana component cannabidiol inhibits beta-amyloid-induced tau protein hyperphosphorylation through Wnt/beta-catenin pathway rescue in PC12 cells. J.Mol.Med.(Berl). 84: 253-258.
708. Booz, G. W. (2011). Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic.Biol.Med. 51: 1054-1061.
709. Esposito, G., Scuderi, C., Savani, C., Steardo, L., Jr. and others. (2007). Cannabidiol in vivo blunts beta-amyloid induced neuroinflammation by suppressing IL-1beta and iNOS expression. Br.J.Pharmacol. 151: 12721279.
710. Esposito, G., Iuvone, T., Savani, C., Scuderi, C. and others. (2007). Opposing control of cannabinoid receptor stimulation on amyloid-beta-induced reactive gliosis: in vitro and in vivo evidence. J.Pharmacol.Exp.Ther. 322: 1144-1152.
711. Walther, S., Mahlberg, R., Eichmann, U., and Kunz, D. (2006). Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacology (Berl). 185: 524-528.
712. Passmore, M. J. (2008). The cannabinoid receptor agonist nabilone for the treatment of dementia-related agitation. Int.J.Geriatr.Psychiatry. 23: 116-117.
713. Krishnan, S., Cairns, R., and Howard, R. (2009). Cannabinoids for the treatment of dementia. Cochrane.Database.Syst.Rev. CD007204.-
714. Klein, T. W. (2005). Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat.Rev.Immunol. 5: 400-411.
715. Nagarkatti, P., Pandey, R., Rieder, S. A., Hegde, V. L. and others. (2009). Cannabinoids as novel anti-inflammatory drugs. Future.Med.Chem. 1: 1333-1349.
716. Stander, S., Schmelz, M., Metze, D., Luger, T. and others. (2005). Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J.Dermatol.Sci. 38: 177-188.
717. Toth, B. I., Dobrosi, N., Dajnoki, A., Czifra, G. and others. (2011). Endocannabinoids modulate human epidermal keratinocyte proliferation and survival via the sequential engagement of cannabinoid receptor-1 and transient receptor potential vanilloid-1. J.Invest Dermatol. 131: 1095-1104.
718. Maccarrone, M., Di Rienzo M., Battista, N., Gasperi, V. and others. (2003). The endocannabinoid system in human keratinocytes. Evidence that anandamide inhibits epidermal differentiation through CB1 receptordependent inhibition of protein kinase C, activation protein-1, and transglutaminase. J.Biol.Chem. 278: 33896-33903.
719. Wilkinson, J. D. and Williamson, E. M. (2007). Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J.Dermatol.Sci. 45: 87-92.
720. Dvorak, M., Watkinson, A., McGlone, F., and Rukwied, R. (2003). Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin. Inflamm.Res. 52: 238-245.
721. Rukwied, R., Watkinson, A., McGlone, F., and Dvorak, M. (2003). Cannabinoid agonists attenuate capsaicininduced responses in human skin. Pain. 102: 283-288.
722. Watson, E. S., Murphy, J. C., and Turner, C. E. (1983). Allergenic properties of naturally occurring cannabinoids. J.Pharm.Sci. 72: 954-955.
723. Williams, C., Thompstone, J., and Wilkinson, M. (2008). Work-related contact urticaria to Cannabis sativa. Contact Dermatitis. 58: 62-63.
724. Mikuriya, T. H. (1969). Marijuana in medicine: past, present and future. Calif.Med. 110: 34-40.
725. Kalant, H. (2001). Medicinal use of cannabis: history and current status. Pain Res.Manag. 6: 80-91.
726. Zuardi, A. W. (2006). History of cannabis as a medicine: a review. Rev.Bras.Psiquiatr. 28: 153-157.
727. Duncan, M., Thomas, A. D., Cluny, N. L., Patel, A. and others. (2008). Distribution and function of monoacylglycerol lipase in the gastrointestinal tract. Am.J.Physiol Gastrointest.Liver Physiol. 295: G1255G1265.
728. Kennedy, P. J., Clarke, G., Quigley, E. M., Groeger, J. A. and others. (2012). Gut memories: towards a cognitive neurobiology of irritable bowel syndrome. Neurosci.Biobehav.Rev. 36: 310-340.
729. Storr, M. A., Yuce, B., Andrews, C. N., and Sharkey, K. A. (2008). The role of the endocannabinoid system in the pathophysiology and treatment of irritable bowel syndrome. Neurogastroenterol.Motil. 20: 857-868.
730. Yao, X., Yang, Y. S., Cui, L. H., Zhao, K. B. and others. (2012). Subtypes of irritable bowel syndrome on Rome III criteria: a multicenter study. J.Gastroenterol.Hepatol. 27: 760-765.
731. Camilleri, M., Carlson, P., McKinzie, S., Grudell, A. and others. (2008). Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation. Am.J.Physiol Gastrointest.Liver Physiol. 294: G13G19.
732. Park, J. M., Choi, M. G., Cho, Y. K., Lee, I. S. and others. (2011). Cannabinoid receptor 1 gene polymorphism and irritable bowel syndrome in the Korean population: a hypothesis-generating study. J.Clin.Gastroenterol. 45: 45-49.
733. Camilleri, M. and Katzka, D. A. (2012). Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome. Am.J.Physiol Gastrointest.Liver Physiol. 302: G1075-G1084.
734. Sanson, M., Bueno, L., and Fioramonti, J. (2006). Involvement of cannabinoid receptors in inflammatory hypersensitivity to colonic distension in rats. Neurogastroenterol.Motil. 18: 949-956.
735. Brusberg, M., Arvidsson, S., Kang, D., Larsson, H. and others. (2009). CB1 receptors mediate the analgesic effects of cannabinoids on colorectal distension-induced visceral pain in rodents. J.Neurosci. 29: 1554-1564.
736. Kimball, E. S., Wallace, N. H., Schneider, C. R., D’Andrea, M. R. and others. (2010). Small intestinal cannabinoid receptor changes following a single colonic insult with oil of mustard in mice. Front Pharmacol. 1: 132-
737. Esfandyari, T., Camilleri, M., Ferber, I., Burton, D. and others. (2006). Effect of a cannabinoid agonist on gastrointestinal transit and postprandial satiation in healthy human subjects: a randomized, placebocontrolled study. Neurogastroenterol.Motil. 18: 831-838.
738. Esfandyari, T., Camilleri, M., Busciglio, I., Burton, D. and others. (2007). Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study. Am.J.Physiol Gastrointest.Liver Physiol. 293: G137-G145.
739. Rao, S. S. and Singh, S. (2010). Clinical utility of colonic and anorectal manometry in chronic constipation. J.Clin.Gastroenterol. 44: 597-609.
740. Coulie, B., Camilleri, M., Bharucha, A. E., Sandborn, W. J. and others. (2001). Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects. Aliment.Pharmacol.Ther. 15: 653-663.
741. Lembo, T., Wright, R. A., Bagby, B., Decker, C. and others. (2001). Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome. Am.J.Gastroenterol. 96: 2662-2670.
742. Wong, B. S., Camilleri, M., Busciglio, I., Carlson, P. and others. (2011). Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome. Gastroenterology. 141: 1638-1647.
743. Wong, B. S., Camilleri, M., Eckert, D., Carlson, P. and others. (2012). Randomized pharmacodynamic and pharmacogenetic trial of dronabinol effects on colon transit in irritable bowel syndrome-diarrhea. Neurogastroenterol.Motil. 24: 358-e169.
744. Di Sabatino, A., Battista, N., Biancheri, P., Rapino, C. and others. (2011). The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease. Mucosal.Immunol. 4: 574-583.
745. Mowat, C., Cole, A., Windsor, A., Ahmad, T. and others. (2011). Guidelines for the management of inflammatory bowel disease in adults. Gut. 60: 571-607.
746. Ligresti, A., Bisogno, T., Matias, I., De, Petrocellis L. and others. (2003). Possible endocannabinoid control of colorectal cancer growth. Gastroenterology. 125: 677-687.
747. Guagnini, F., Valenti, M., Mukenge, S., Matias, I. and others. (2006). Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P. Gut. 55: 946-953.
748. D’Argenio, G., Petrosino, S., Gianfrani, C., Valenti, M. and others. (2007). Overactivity of the intestinal endocannabinoid system in celiac disease and in methotrexate-treated rats. J.Mol.Med. 85: 523-530.
749. Massa, F., Marsicano, G., Hermann, H., Cannich, A. and others. (2004). The endogenous cannabinoid system protects against colonic inflammation. J.Clin.Invest. 113: 1202-1209.
750. D’Argenio, G., Valenti, M., Scaglione, G., Cosenza, V. and others. (2006). Up-regulation of anandamide levels as an endogenous mechanism and a pharmacological strategy to limit colon inflammation. FASEB J. 20: 568570.
751. Kimball, E. S., Schneider, C. R., Wallace, N. H., and Hornby, P. J. (2006). Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium. Am.J.Physiol Gastrointest.Liver Physiol. 291: G364-G371.
752. Storr, M., Emmerdinger, D., Diegelmann, J., Yuce, B. and others. (2009). The role of fatty acid hydrolase gene variants in inflammatory bowel disease. Aliment.Pharmacol.Ther. 29: 542-551.
753. Engel, M. A., Kellermann, C. A., Burnat, G., Hahn, E. G. and others. (2010). Mice lacking cannabinoid CB1-, CB2receptors or both receptors show increased susceptibility to trinitrobenzene sulfonic acid (TNBS)-induced colitis. J.Physiol Pharmacol. 61: 89-97.
754. Jamontt, J. M., Molleman, A., Pertwee, R. G., and Parsons, M. E. (2010). The effects of Delta-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis. Br.J.Pharmacol. 160: 712-723.
755. Di Paola, R., Mazzon, E., Patel, N. S., Genovese, T. and others. (2005). Beneficial effects of GW274150 treatment on the development of experimental colitis induced by dinitrobenzene sulfonic acid. Eur.J.Pharmacol. 507: 281-289.
756. Storr, M. A., Keenan, C. M., Zhang, H., Patel, K. D. and others. (2009). Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitis. Inflamm.Bowel.Dis. 15: 1678-1685.
757. Borrelli, F., Aviello, G., Romano, B., Orlando, P. and others. (2009). Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis. J.Mol.Med.(Berl). 87: 1111-1121.
758. Schicho, R. and Storr, M. (2012). Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology. 89: 149-155.
759. Alhouayek, M., Lambert, D. M., Delzenne, N. M., Cani, P. D. and others. (2011). Increasing endogenous 2arachidonoylglycerol levels counteracts colitis and related systemic inflammation. FASEB J. 25: 27112721.
760. Singh, U. P., Singh, N. P., Singh, B., Price, R. L. and others. (2012). Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10(-/-) mice by attenuating the activation of T cells and promoting their apoptosis. Toxicol.Appl.Pharmacol. 258: 256-267.
761. Izzo, A. A., Capasso, R., Aviello, G., Borrelli, F. and others. (2012). Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. Br.J.Pharmacol. 166: 1444-1460.
762. Klooker, T. K., Leliefeld, K. E., van den Wijngaard, R. M., and Boeckxstaens, G. E. (2011). The cannabinoid receptor agonist delta-9-tetrahydrocannabinol does not affect visceral sensitivity to rectal distension in healthy volunteers and IBS patients. Neurogastroenterol.Motil. 23: 30-5, e2.
763. Tam, J., Liu, J., Mukhopadhyay, B., Cinar, R. and others. (2011). Endocannabinoids in liver disease. Hepatology. 53: 346-355.
764. Teixeira-Clerc, F., Belot, M. P., Manin, S., Deveaux, V. and others. (2010). Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration. Hepatology. 52: 1046-1059.
765. Giannone, F. A., Baldassarre, M., Domenicali, M., Zaccherini, G. and others. (2012). Reversal of liver fibrosis by the antagonism of endocannabinoid CB1 receptor in a rat model of CCl(4)-induced advanced cirrhosis. Lab Invest. 92: 384-395.
766. Lim, M. P., Devi, L. A., and Rozenfeld, R. (2011). Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis. Cell Death.Dis. 2: e170-
767. Mukhopadhyay, P., Rajesh, M., Horvath, B., Batkai, S. and others. (2011). Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death. Free Radic.Biol.Med. 50: 1368-1381.
768. Fouad, A. A. and Jresat, I. (2011). Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats. Eur.J.Pharmacol. 670: 216-223.
769. Avraham, Y., Grigoriadis, N., Poutahidis, T., Vorobiev, L. and others. (2011). Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. Br.J.Pharmacol. 162: 1650-1658.
770. Batkai, S., Mukhopadhyay, P., Horvath, B., Rajesh, M. and others. (2012). Delta8-Tetrahydrocannabivarin prevents hepatic ischaemia/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors. Br.J.Pharmacol. 165: 2450-2461.
771. Silvestri, C., Ligresti, A., and Di, Marzo, V. (2011). Peripheral effects of the endocannabinoid system in energy homeostasis: adipose tissue, liver and skeletal muscle. Rev.Endocr.Metab Disord. 12: 153-162.
772. O’Hare, J. D., Zielinski, E., Cheng, B., Scherer, T. and others. (2011). Central endocannabinoid signaling regulates hepatic glucose production and systemic lipolysis. Diabetes. 60: 1055-1062.
773. Engeli, S. (2012). Central and peripheral cannabinoid receptors as therapeutic targets in the control of food intake and body weight. Handb.Exp.Pharmacol. 357-381.
774. Li, C., Jones, P. M., and Persaud, S. J. (2011). Role of the endocannabinoid system in food intake, energy homeostasis and regulation of the endocrine pancreas. Pharmacol.Ther. 129: 307-320.
775. Osei-Hyiaman, D., Depetrillo, M., Pacher, P., Liu, J. and others. (2005). Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J.Clin.Invest. 115: 12981305.
776. Pagano, C., Pilon, C., Calcagno, A., Urbanet, R. and others. (2007). The endogenous cannabinoid system stimulates glucose uptake in human fat cells via phosphatidylinositol 3-kinase and calcium-dependent mechanisms. J.Clin.Endocrinol.Metab. 92: 4810-4819.
777. Cardinal, P., Bellocchio, L., Clark, S., Cannich, A. and others. (2012). Hypothalamic CB1 cannabinoid receptors regulate energy balance in mice. Endocrinology. 153: 4136-4143.
778. Cota, D., Marsicano, G., Tschop, M., Grubler, Y. and others. (2003). The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J.Clin.Invest. 112: 423-431.
779. Quarta, C., Bellocchio, L., Mancini, G., Mazza, R. and others. (2010). CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance. Cell Metab. 11: 273-285.
780. Osei-Hyiaman, D., Liu, J., Zhou, L., Godlewski, G. and others. (2008). Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J.Clin.Invest. 118: 3160-3169.
781. Liu, J., Zhou, L., Xiong, K., Godlewski, G. and others. (2012). Hepatic cannabinoid receptor-1 mediates diet-induced insulin resistance via inhibition of insulin signaling and clearance in mice. Gastroenterology. 142: 12181228.
782. Ravinet, Trillou C., Arnone, M., Delgorge, C., Gonalons, N. and others. (2003). Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am.J.Physiol Regul.Integr.Comp Physiol. 284: R345-R353.
783. Poirier, B., Bidouard, J. P., Cadrouvele, C., Marniquet, X. and others. (2005). The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. Diabetes Obes.Metab. 7: 65-72.
784. Jbilo, O., Ravinet-Trillou, C., Arnone, M., Buisson, I. and others. (2005). The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. FASEB J. 19: 1567-1569.
785. Watanabe, T., Kubota, N., Ohsugi, M., Kubota, T. and others. (2009). Rimonabant ameliorates insulin resistance via both adiponectin-dependent and adiponectin-independent pathways. J.Biol.Chem. 284: 1803-1812.
786. Jourdan, T., Djaouti, L., Demizieux, L., Gresti, J. and others. (2010). CB1 antagonism exerts specific molecular effects on visceral and subcutaneous fat and reverses liver steatosis in diet-induced obese mice. Diabetes. 59: 926-934.
787. Crespillo, A., Suarez, J., Bermudez-Silva, F. J., Rivera, P. and others. (2011). Expression of the cannabinoid system in muscle: effects of a high-fat diet and CB1 receptor blockade. Biochem.J. 433: 175-185.
788. Bell-Anderson, K. S., Aouad, L., Williams, H., Sanz, F. R. and others. (2011). Coordinated improvement in glucose tolerance, liver steatosis and obesity-associated inflammation by cannabinoid 1 receptor antagonism in fat Aussie mice. Int.J.Obes.(Lond). 35: 1539-1548.
789. Van Gaal, L. F., Rissanen, A. M., Scheen, A. J., Ziegler, O. and others. (2005). Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 365: 1389-1397.
790. Despres, J. P., Golay, A., and Sjostrom, L. (2005). Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N.Engl.J.Med. 353: 2121-2134.
791. Pi-Sunyer, F. X., Aronne, L. J., Heshmati, H. M., Devin, J. and others. (2006). Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA. 295: 761-775.
792. Scheen, A. J., Finer, N., Hollander, P., Jensen, M. D. and others. (2006). Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet. 368: 1660-1672.
793. Van Gaal, L. F., Scheen, A. J., Rissanen, A. M., Rossner, S. and others. (2008). Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors: two year results from the RIO-Europe Study. Eur.Heart J. 29: 1761-1771.
794. Van Gaal, L., Pi-Sunyer, X., Despres, J. P., McCarthy, C. and others. (2008). Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care. 31 Suppl 2: S229-S240.
795. Despres, J. P., Ross, R., Boka, G., Almeras, N. and others. (2009). Effect of rimonabant on the high-triglyceride/ low-HDL-cholesterol dyslipidemia, intraabdominal adiposity, and liver fat: the ADAGIO-Lipids trial. Arterioscler.Thromb.Vasc.Biol. 29: 416-423.
796. Hayatbakhsh, M. R., O’Callaghan, M. J., Mamun, A. A., Williams, G. M. and others. (2010). Cannabis use and obesity and young adults. Am.J.Drug Alcohol Abuse. 36: 350-356.
797. Le Strat, Y. and Le Foll, B. (2011). Obesity and cannabis use: results from 2 representative national surveys. Am.J.Epidemiol. 174: 929-933.
798. Deveaux, V., Cadoudal, T., Ichigotani, Y., Teixeira-Clerc, F. and others. (2009). Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis. PLoS.One. 4: e5844-
799. Agudo, J., Martin, M., Roca, C., Molas, M. and others. (2010). Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age. Diabetologia. 53: 2629-2640.
800. Levendal, R. A., Schumann, D., Donath, M., and Frost, C. L. (2012). Cannabis exposure associated with weight reduction and beta-cell protection in an obese rat model. Phytomedicine. 19: 575-582.
801. Li, C., Bowe, J. E., Huang, G. C., Amiel, S. A. and others. (2011). Cannabinoid receptor agonists and antagonists stimulate insulin secretion from isolated human islets of Langerhans. Diabetes Obes.Metab. 13: 903-910.
802. Li, C., Vilches-Flores, A., Zhao, M., Amiel, S. A. and others. (2012). Expression and function of monoacylglycerol lipase in mouse beta-cells and human islets of Langerhans. Cell Physiol Biochem. 30: 347-358.
803. Bermudez-Silva, F. J., Suarez, J., Baixeras, E., Cobo, N. and others. (2008). Presence of functional cannabinoid receptors in human endocrine pancreas. Diabetologia. 51: 476-487.
804. De Pasquale, A., Costa, G., and Trovato, A. (1978). The influence of cannabis on glucoregulation. Bull.Narc. 30: 3341.
805. Bermudez-Siva, F. J., Serrano, A., Diaz-Molina, F. J., Sanchez, Vera, I and others. (2006). Activation of cannabinoid CB1 receptors induces glucose intolerance in rats. Eur.J.Pharmacol. 531: 282-284.
806. Hollister, L. E. and Reaven, G. M. (1974). Delta-9-tetrahydrocannabinol and glucose tolerance. Clin.Pharmacol.Ther. 16: 297-302.
807. Rajavashisth, T. B., Shaheen, M., Norris, K. C., Pan, D. and others. (2012). Decreased prevalence of diabetes in marijuana users: cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) III. BMJ Open. 2: e000494-
808. Michalski, C. W., Laukert, T., Sauliunaite, D., Pacher, P. and others. (2007). Cannabinoids ameliorate pain and reduce disease pathology in cerulein-induced acute pancreatitis. Gastroenterology. 132: 1968-1978.
809. Michalski, C. W., Maier, M., Erkan, M., Sauliunaite, D. and others. (2008). Cannabinoids reduce markers of inflammation and fibrosis in pancreatic stellate cells. PLoS.One. 3: e1701-
810. Matsuda, K., Mikami, Y., Takeda, K., Fukuyama, S. and others. (2005). The cannabinoid 1 receptor antagonist, AM251, prolongs the survival of rats with severe acute pancreatitis. Tohoku J.Exp.Med. 207: 99-107.
811. Dembinski, A., Warzecha, Z., Ceranowicz, P., Dembinski, M. and others. (2006). Cannabinoids in acute gastric damage and pancreatitis. J.Physiol Pharmacol. 57 Suppl 5: 137-154.
812. Zyromski, N. J., Mathur, A., Pitt, H. A., Wade, T. E. and others. (2009). Cannabinoid receptor-1 blockade attenuates acute pancreatitis in obesity by an adiponectin mediated mechanism. J.Gastrointest.Surg. 13: 831-838.
813. Petrella, C., Agostini, S., Alema’, G. S., Casolini, P. and others. (2010). Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo induces dual effects on the course of acute pancreatitis. Neurogastroenterol.Motil. 22: 1248-56, e323.
814. Malfitano, A. M., Ciaglia, E., Gangemi, G., Gazzerro, P. and others. (2011). Update on the endocannabinoid system as an anticancer target. Expert.Opin.Ther.Targets. 15: 297-308.
815. Pagotto, U., Marsicano, G., Fezza, F., Theodoropoulou, M. and others. (2001). Normal human pituitary gland and pituitary adenomas express cannabinoid receptor type 1 and synthesize endogenous cannabinoids: first evidence for a direct role of cannabinoids on hormone modulation at the human pituitary level. J.Clin.Endocrinol.Metab. 86: 2687-2696.
816. Schmid, P. C., Wold, L. E., Krebsbach, R. J., Berdyshev, E. V. and others. (2002). Anandamide and other Nacylethanolamines in human tumors. Lipids. 37: 907-912.
817. Nithipatikom, K., Endsley, M. P., Isbell, M. A., Falck, J. R. and others. (2004). 2-arachidonoylglycerol: a novel inhibitor of androgen-independent prostate cancer cell invasion. Cancer Res. 64: 8826-8830.
818. Petersen, G., Moesgaard, B., Schmid, P. C., Schmid, H. H. and others. (2005). Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non-tumour brain tissue. J.Neurochem. 93: 299-309.
819. Cianchi, F., Papucci, L., Schiavone, N., Lulli, M. and others. (2008). Cannabinoid receptor activation induces apoptosis through tumor necrosis factor alpha-mediated ceramide de novo synthesis in colon cancer cells. Clin.Cancer Res. 14: 7691-7700.
820. Grimaldi, C. and Capasso, A. (2011). The endocannabinoid system in the cancer therapy: an overview. Curr.Med.Chem. 18: 1575-1583.
821. Pisanti, S. and Bifulco, M. (2009). Endocannabinoid system modulation in cancer biology and therapy. Pharmacol.Res. 60: 107-116.
822. Stella, N. (2010). Cannabinoid and cannabinoid-like receptors in microglia, astrocytes, and astrocytomas. Glia. 58: 1017-1030.
823. McAllister, S. D., Chan, C., Taft, R. J., Luu, T. and others. (2005). Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. J.Neurooncol. 74: 31-40.
824. Cudaback, E., Marrs, W., Moeller, T., and Stella, N. (2010). The expression level of CB1 and CB2 receptors determines their efficacy at inducing apoptosis in astrocytomas. PLoS.One. 5: e8702.-
825. Caffarel, M. M., Sarrio, D., Palacios, J., Guzman, M. and others. (2006). Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 66: 6615-6621.
826. McKallip, R. J., Nagarkatti, M., and Nagarkatti, P. S. (2005). Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J.Immunol. 174: 3281-3289.
827. Takeda, S., Yamaori, S., Motoya, E., Matsunaga, T. and others. (2008). Delta(9)-Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling. Toxicology. 245: 141-146.
828. Ligresti, A., Moriello, A. S., Starowicz, K., Matias, I. and others. (2006). Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J.Pharmacol.Exp.Ther. 318: 13751387.
829. Preet, A., Ganju, R. K., and Groopman, J. E. (2008). Delta9-Tetrahydrocannabinol inhibits epithelial growth factorinduced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene. 27: 339346.
830. Greenhough, A., Patsos, H. A., Williams, A. C., and Paraskeva, C. (2007). The cannabinoid delta(9)tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Int.J.Cancer. 121: 2172-2180.
831. Galve-Roperh, I., Sanchez, C., Cortes, M. L., Gomez, del Pulgar and others. (2000). Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat.Med. 6: 313-319.
832. Caffarel, M. M., Andradas, C., Mira, E., Perez-Gomez, E. and others. (2010). Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Mol.Cancer. 9: 196-206.
833. McAllister, S. D., Murase, R., Christian, R. T., Lau, D. and others. (2010). Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Res.Treat. 129: 37-47.
834. Carracedo, A., Lorente, M., Egia, A., Blazquez, C. and others. (2006). The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell. 9: 301-312.
835. Torres, S., Lorente, M., Rodriguez-Fornes, F., Hernandez-Tiedra, S. and others. (2011). A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol.Cancer Ther. 10: 90-103.
836. Guzman, M., Duarte, M. J., Blazquez, C., Ravina, J. and others. (2006). A pilot clinical study of Delta9tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br.J.Cancer. 95: 197-203.
837. Dinnes, J., Cave, C., Huang, S., and Milne, R. (2002). A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma. Br.J.Cancer. 86: 501-505.
838. Brem, H., Piantadosi, S., Burger, P. C., Walker, M. and others. (1995). Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet. 345: 1008-1012.
839. Marcu, J. P., Christian, R. T., Lau, D., Zielinski, A. J. and others. (2010). Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Mol.Cancer Ther. 9: 180-189.
840. Velasco, G., Carracedo, A., Blazquez, C., Lorente, M. and others. (2007). Cannabinoids and gliomas. Mol.Neurobiol. 36: 60-67.
841. Parolaro, D. and Massi, P. (2008). Cannabinoids as potential new therapy for the treatment of gliomas. Expert.Rev.Neurother. 8: 37-49.
842. Alexander, A., Smith, P. F., and Rosengren, R. J. (2009). Cannabinoids in the treatment of cancer. Cancer Lett. 285: 6-12.
843. Steffens, S., Veillard, N. R., Arnaud, C., Pelli, G. and others. (2005). Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature. 434: 782-786.
844. Sugamura, K., Sugiyama, S., Nozaki, T., Matsuzawa, Y. and others. (2009). Activated endocannabinoid system in coronary artery disease and antiinflammatory effects of cannabinoid 1 receptor blockade on macrophages. Circulation. 119: 28-36.
845. Zhao, Y., Yuan, Z., Liu, Y., Xue, J. and others. (2010). Activation of cannabinoid CB2 receptor ameliorates atherosclerosis associated with suppression of adhesion molecules. J.Cardiovasc.Pharmacol. 55: 292-298.
846. Hoyer, F. F., Steinmetz, M., Zimmer, S., Becker, A. and others. (2011). Atheroprotection via cannabinoid receptor-2 is mediated by circulating and vascular cells in vivo. J.Mol.Cell Cardiol. 51: 1007-1014.
847. Willecke, F., Zeschky, K., Ortiz, Rodriguez A., Colberg, C. and others. (2011). Cannabinoid receptor 2 signaling does not modulate atherogenesis in mice. PLoS.One. 6: e19405-
848. Netherland, C. D., Pickle, T. G., Bales, A., and Thewke, D. P. (2010). Cannabinoid receptor type 2 (CB2) deficiency alters atherosclerotic lesion formation in hyperlipidemic Ldlr-null mice. Atherosclerosis. 213: 102-108.
849. Rajesh, M., Mukhopadhyay, P., Hasko, G., Liaudet, L. and others. (2010). Cannabinoid-1 receptor activation induces reactive oxygen species-dependent and -independent mitogen-activated protein kinase activation and cell death in human coronary artery endothelial cells. Br.J.Pharmacol. 160: 688-700.
850. Singla, S., Sachdeva, R., and Mehta, J. L. (2012). Cannabinoids and atherosclerotic coronary heart disease. Clin.Cardiol. 35: 329-335.
851. Montecucco, F. and Di Marzo, V. (2012). At the heart of the matter: the endocannabinoid system in cardiovascular function and dysfunction. Trends Pharmacol.Sci. 33: 331-340.
852. Steffens, S. and Pacher, P. (2012). Targeting cannabinoid receptor CB(2) in cardiovascular disorders: promises and controversies. Br.J.Pharmacol. 167: 313-323.
853. Takeda, S., Usami, N., Yamamoto, I., and Watanabe, K. (2009). Cannabidiol-2′,6′-dimethyl ether, a cannabidiol derivative, is a highly potent and selective 15-lipoxygenase inhibitor. Drug Metab Dispos. 37: 1733-1737.
854. Hezode, C., Zafrani, E. S., Roudot-Thoraval, F., Costentin, C. and others. (2008). Daily cannabis use: a novel risk factor of steatosis severity in patients with chronic hepatitis C. Gastroenterology. 134: 432-439.
855. Barrett, S. P., Darredeau, C., and Pihl, R. O. (2006). Patterns of simultaneous polysubstance use in drug using university students. Hum.Psychopharmacol. 21: 255-263.
856. Agrawal, A. and Lynskey, M. T. (2007). Does gender contribute to heterogeneity in criteria for cannabis abuse and dependence? Results from the national epidemiological survey on alcohol and related conditions. Drug Alcohol Depend. 88: 300-307.
857. Kuepper, R., van, Os J., Lieb, R., Wittchen, H. U. and others. (2011). Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ. 342: d738.-
858. Budney, A. J. and Hughes, J. R. (2006). The cannabis withdrawal syndrome. Curr.Opin.Psychiatry. 19: 233-238.
859. National Institute on Drug Abuse. NIDA InfoFacts: Marijuana. 2009.
860. Mathew, R. J., Wilson, W. H., Coleman, R. E., Turkington, T. G. and others. (1997). Marijuana intoxication and brain activation in marijuana smokers. Life Sci. 60: 2075-2089.
861. Ramaekers, J. G., Kauert, G., van, Ruitenbeek P., Theunissen, E. L. and others. (2006). High-potency marijuana impairs executive function and inhibitory motor control. Neuropsychopharmacology. 31: 2296-2303.
862. Kurzthaler, I., Hummer, M., Miller, C., Sperner-Unterweger, B. and others. (1999). Effect of cannabis use on cognitive functions and driving ability. J.Clin.Psychiatry. 60: 395-399.
863. Reisfield, G. M., Wasan, A. D., and Jamison, R. N. (2009). The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature. Pain Med. 10: 1434-1441.
864. Ashton, C. H. (1999). Adverse effects of cannabis and cannabinoids. Br.J.Anaesth. 83: 637-649.
865. de Jong, F. A., Engels, F. K., Mathijssen, R. H., van, Zuylen L. and others. (2005). Medicinal cannabis in oncology practice: still a bridge too far? J.Clin.Oncol. 23: 2886-2891.
866. Ballard, M. E. and de, Wit H. (2011). Combined effects of acute, very-low-dose ethanol and delta(9)tetrahydrocannabinol in healthy human volunteers. Pharmacol.Biochem.Behav. 97: 627-631.
867. Battista, N., Pasquariello, N., Di, Tommaso M., and Maccarrone, M. (2008). Interplay between endocannabinoids, steroids and cytokines in the control of human reproduction. J.Neuroendocrinol. 20 Suppl 1: 82-89.
868. Habayeb, O. M., Taylor, A. H., Finney, M., Evans, M. D. and others. (2008). Plasma anandamide concentration and pregnancy outcome in women with threatened miscarriage. JAMA. 299: 1135-1136.
869. Fried, P. A. (2002). Conceptual issues in behavioral teratology and their application in determining long-term sequelae of prenatal marihuana exposure. J.Child Psychol.Psychiatry. 43: 81-102.
870. Richardson, G. A., Ryan, C., Willford, J., Day, N. L. and others. (2002). Prenatal alcohol and marijuana exposure: effects on neuropsychological outcomes at 10 years. Neurotoxicol.Teratol. 24: 309-320.
871. Perez-Reyes, M. and Wall, M. E. (1982). Presence of delta9-tetrahydrocannabinol in human milk. N.Engl.J.Med. 307: 819-820.
872. Garry, A., Rigourd, V., Amirouche, A., Fauroux, V. and others. (2009). Cannabis and breastfeeding. J.Toxicol. 2009: 596149.-
873. Chait, L. D. and Perry, J. L. (1994). Acute and residual effects of alcohol and marijuana, alone and in combination, on mood and performance. Psychopharmacology (Berl). 115: 340-349.
874. Lukas, S. E. and Orozco, S. (2001). Ethanol increases plasma Delta(9)-tetrahydrocannabinol (THC) levels and subjective effects after marihuana smoking in human volunteers. Drug Alcohol Depend. 64: 143-149.
875. Li, X. Q., Andersson, T. B., Ahlstrom, M., and Weidolf, L. (2004). Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 32: 821-827.
876. Spina, E., Santoro, V., and D’Arrigo, C. (2008). Clinically relevant pharmacokinetic drug interactions with secondgeneration antidepressants: an update. Clin.Ther. 30: 1206-1227.
877. Davison, S. N. and Davison, J. S. (2011). Is there a legitimate role for the therapeutic use of cannabinoids for symptom management in chronic kidney disease? J.Pain Symptom.Manage. 41: 768-778.
878. Ellis, G. M., Jr., Mann, M. A., Judson, B. A., Schramm, N. T. and others. (1985). Excretion patterns of cannabinoid metabolites after last use in a group of chronic users. Clin.Pharmacol.Ther. 38: 572-578.
879. Lowe, R. H., Abraham, T. T., Darwin, W. D., Herning, R. and others. (2009). Extended urinary Delta9tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure. Drug Alcohol Depend. 105: 24-32.
880. Wang, T., Collet, J. P., Shapiro, S., and Ware, M. A. (2008). Adverse effects of medical cannabinoids: a systematic review. CMAJ. 178: 1669-1678.
881. Amos, A., Wiltshire, S., Bostock, Y., Haw, S. and others. (2004). ‘You can’t go without a fag…you need it for your hash’–a qualitative exploration of smoking, cannabis and young people. Addiction. 99: 77-81.
882. Hezode, C., Roudot-Thoraval, F., Nguyen, S., Grenard, P. and others. (2005). Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology. 42: 63-71.
883. Vandrey, R. G., Budney, A. J., Hughes, J. R., and Liguori, A. (2008). A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances. Drug Alcohol Depend. 92: 4854.
884. Agrawal, A., Scherrer, J. F., Lynskey, M. T., Sartor, C. E. and others. (2011). Patterns of use, sequence of onsets and correlates of tobacco and cannabis. Addict.Behav. 36: 1141-1147.
885. Wu, T. C., Tashkin, D. P., Djahed, B., and Rose, J. E. (1988). Pulmonary hazards of smoking marijuana as compared with tobacco. N.Engl.J.Med. 318: 347-351.
886. Taylor, D. R., Fergusson, D. M., Milne, B. J., Horwood, L. J. and others. (2002). A longitudinal study of the effects of tobacco and cannabis exposure on lung function in young adults. Addiction. 97: 1055-1061.
887. Tashkin, D. P. Marihuana and the lung. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
888. Taylor, D. R., Poulton, R., Moffitt, T. E., Ramankutty, P. and others. (2000). The respiratory effects of cannabis dependence in young adults. Addiction. 95: 1669-1677.
889. Denning, D. W., Follansbee, S. E., Scolaro, M., Norris, S. and others. (1991). Pulmonary aspergillosis in the acquired immunodeficiency syndrome. N.Engl.J.Med. 324: 654-662.
890. Moore, B. A., Augustson, E. M., Moser, R. P., and Budney, A. J. (2005). Respiratory effects of marijuana and tobacco use in a U.S. sample. J.Gen.Intern.Med. 20: 33-37.
891. Roth, M. D., Whittaker, K., Salehi, K., Tashkin, D. P. and others. (2004). Mechanisms for impaired effector function in alveolar macrophages from marijuana and cocaine smokers. J.Neuroimmunol. 147: 82-86.
892. LIU, D. Z., HU, C. M., HUANG, C. H., WEY, S. P. and others. (2010). Cannabidiol attenuates delayed-type hypersensitivity reactions via suppressing T-cell and macrophage reactivity. Acta Pharmacol.Sin. 31: 1611-1617.
893. Kozela, E., Pietr, M., Juknat, A., Rimmerman, N. and others. (2010). Cannabinoids Delta(9)-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-kappaB and interferonbeta/STAT proinflammatory pathways in BV-2 microglial cells. J.Biol.Chem. 285: 1616-1626.
894. Reiss, C. S. (2010). Cannabinoids and viral infections. Pharmaceuticals (Basel). 3: 1873-1886.
895. Mishkin, E. M. and Cabral, G. A. (1985). delta-9-Tetrahydrocannabinol decreases host resistance to herpes simplex virus type 2 vaginal infection in the B6C3F1 mouse. J.Gen.Virol. 66 ( Pt 12): 2539-2549.
896. Cabral, G. A., McNerney, P. J., and Mishkin, E. M. (1986). Delta-9-tetrahydrocannabinol enhances release of herpes simplex virus type 2. J.Gen.Virol. 67 ( Pt 9): 2017-2022.
897. Roth, M. D., Baldwin, G. C., and Tashkin, D. P. (2002). Effects of delta-9-tetrahydrocannabinol on human immune function and host defense. Chem.Phys.Lipids. 121: 229-239.
898. Buchweitz, J. P., Karmaus, P. W., Harkema, J. R., Williams, K. J. and others. (2007). Modulation of airway responses to influenza A/PR/8/34 by Delta9-tetrahydrocannabinol in C57BL/6 mice. J.Pharmacol.Exp.Ther. 323: 675-683.
899. Zhang, X., Wang, J. F., Kunos, G., and Groopman, J. E. (2007). Cannabinoid modulation of Kaposi’s sarcomaassociated herpesvirus infection and transformation. Cancer Res. 67: 7230-7237.
900. Herrera, R. A., Oved, J. H., and Reiss, C. S. (2008). Disruption of IFN-gamma- mediated antiviral activity in neurons: the role of cannabinoids. Viral Immunol. 21: 141-152.
901. Bredt, B. M., Higuera-Alhino, D., Shade, S. B., Hebert, S. J. and others. (2002). Short-term effects of cannabinoids on immune phenotype and function in HIV-1-infected patients. J.Clin.Pharmacol. 42: 82S-89S.
902. Chao, C., Jacobson, L. P., Tashkin, D., Martinez-Maza, O. and others. (2008). Recreational drug use and T lymphocyte subpopulations in HIV-uninfected and HIV-infected men. Drug Alcohol Depend. 94: 165-171.
903. Di Franco, M. J., Sheppard, H. W., Hunter, D. J., Tosteson, T. D. and others. (1996). The lack of association of marijuana and other recreational drugs with progression to AIDS in the San Francisco Men’s Health Study. Ann.Epidemiol. 6: 283-289.
904. Ishida, J. H., Peters, M. G., Jin, C., Louie, K. and others. (2008). Influence of cannabis use on severity of hepatitis C disease. Clin.Gastroenterol.Hepatol. 6: 69-75.
905. Bonn-Miller, M. O., Oser, M. L., Bucossi, M. M., and Trafton, J. A. (2012). Cannabis use and HIV antiretroviral therapy adherence and HIV-related symptoms (in press). J.Behav.Med.
906. Rossato, M., Pagano, C., and Vettor, R. (2008). The cannabinoid system and male reproductive functions. J.Neuroendocrinol. 20 Suppl 1: 90-93.
907. Hembree, W. C., Nahas, G. G., Zeidenberg, P., and Huang, H. F. S. Changes in human spermatozoa associated with high-dose marihuana smoking. Marihuana and medicine. Nahas, G. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa: Humana Press, 1999.
908. Hong, C. Y., Chaput de Saintonge, D. M., Turner, P., and Fairbairn, J. W. (1982). Comparison of the inhibitory action of delta-9-tetrahydrocannabinol and petroleum spirit extract of herbal cannabis on human sperm motility. Hum.Toxicol. 1: 151-154.
909. Whan, L. B., West, M. C., McClure, N., and Lewis, S. E. (2006). Effects of delta-9-tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro. Fertil.Steril. 85: 653660.
910. Lacson, J. C., Carroll, J. D., Tuazon, E., Castelao, E. J. and others. (2012). Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer. 118: 5374-5383.
911. Zuckerman, B., Frank, D. A., Hingson, R., Amaro, H. and others. (1989). Effects of maternal marijuana and cocaine use on fetal growth. N.Engl.J.Med. 320: 762-768.
912. Hurd, Y. L., Wang, X., Anderson, V., Beck, O. and others. (2005). Marijuana impairs growth in mid-gestation fetuses. Neurotoxicol.Teratol. 27: 221-229.
913. El-Marroun, H, Tiemeier, H, Steegers, E. A, Jaddoe, V. W and others. (2009). Intrauterine Cannabis Exposure Affects Fetal Growth Trajectories: The Generation R Study. J.Am.Acad.Child Adolesc.Psychiatry. 48: 1173-1181.
914. Gray, T. R., Eiden, R. D., Leonard, K. E., Connors, G. J. and others. (2010). Identifying prenatal cannabis exposure and effects of concurrent tobacco exposure on neonatal growth. Clin.Chem. 56: 1442-1450.
915. Scragg, R. K., Mitchell, E. A., Ford, R. P., Thompson, J. M. and others. (2001). Maternal cannabis use in the sudden death syndrome. Acta Paediatr. 90: 57-60.
916. Shiono, P. H., Klebanoff, M. A., Nugent, R. P., Cotch, M. F. and others. (1995). The impact of cocaine and marijuana use on low birth weight and preterm birth: a multicenter study. Am.J.Obstet.Gynecol. 172: 1927.
917. Fried, P. A., Watkinson, B., and Gray, R. (1999). Growth from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana. Neurotoxicol.Teratol. 21: 513-525.
918. van Gelder, M. M., Reefhuis, J., Caton, A. R., Werler, M. M. and others. (2010). Characteristics of pregnant illicit drug users and associations between cannabis use and perinatal outcome in a population-based study. Drug Alcohol Depend. 109: 243-247.
919. Ahmad, G. R. and Ahmad, N. (1990). Passive consumption of marijuana through milk: a low level chronic exposure to delta-9-tetrahydrocannabinol(THC). J.Toxicol.Clin.Toxicol. 28: 255-260.
920. Astley, S. J. and Little, R. E. (1990). Maternal marijuana use during lactation and infant development at one year. Neurotoxicol.Teratol. 12: 161-168.
921. Mittleman, M. A. and Mostofsky, E. (2011). Physical, psychological and chemical triggers of acute cardiovascular events: preventive strategies. Circulation. 124: 346-354.
922. Aronow, W. S. and Cassidy, J. (1974). Effect of marihuana and placebo-marihuana smoking on angina pectoris. N.Engl.J.Med. 291: 65-67.
923. Sidney, S. (2002). Cardiovascular consequences of marijuana use. J.Clin.Pharmacol. 42: 64S-70S.
924. Fisher, B. A., Ghuran, A., Vadamalai, V., and Antonios, T. F. (2005). Cardiovascular complications induced by cannabis smoking: a case report and review of the literature. Emerg.Med.J. 22: 679-680.
925. Chesher, G. and Hall, W. Effects of cannabis on the cardiovascular and gastrointestinal systems. The health effects of cannabis. Kalant, H., Corrigall, W., Hall, W., and Smart, R. Toronto: Centre of Addiction and Mental Health, 1999.
926. Merritt, J. C., Cook, C. E., and Davis, K. H. (1982). Orthostatic hypotension after delta 9-tetrahydrocannabinol marihuana inhalation. Ophthalmic Res. 14: 124-128.
927. Purnell, J. Q., Zambon, A., Knopp, R. H., Pizzuti, D. J. and others. (2000). Effect of ritonavir on lipids and postheparin lipase activities in normal subjects. AIDS. 14: 51-57.
928. Cottencin, O., Karila, L., Lambert, M., Arveiller, C. and others. (2010). Cannabis arteritis: review of the literature. J.Addict.Med. 4: 191-196.
929. Noel, B., Ruf, I., and Panizzon, R. G. (2008). Cannabis arteritis. J.Am.Acad.Dermatol. 58: S65-S67.
930. Combemale, P., Consort, T., Denis-Thelis, L., Estival, J. L. and others. (2005). Cannabis arteritis. Br.J.Dermatol. 152: 166-169.
931. Disdier, P., Granel, B., Serratrice, J., Constans, J. and others. (2001). Cannabis arteritis revisited–ten new case reports. Angiology. 52: 1-5.
932. Wolff, V., Lauer, V., Rouyer, O., Sellal, F. and others. (2011). Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction: a prospective study in 48 consecutive young patients. Stroke. 42: 1778-1780.
933. Cox, B., Chhabra, A., Adler, M., Simmons, J. and others. (2012). Cannabinoid hyperemesis syndrome: case report of a paradoxical reaction with heavy marijuana use. Case.Report.Med. 2012: 757696-
934. Batkai, S., Jarai, Z., Wagner, J. A., Goparaju, S. K. and others. (2001). Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat.Med. 7: 827-832.
935. Fernandez-Rodriguez, C. M., Romero, J., Petros, T. J., Bradshaw, H. and others. (2004). Circulating endogenous cannabinoid anandamide and portal, systemic and renal hemodynamics in cirrhosis. Liver Int. 24: 477-483.
936. Julien, B., Grenard, P., Teixeira-Clerc, F., Van Nhieu, J. T. and others. (2005). Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology. 128: 742-755.
937. Teixeira-Clerc, F., Julien, B., Grenard, P., Tran Van, Nhieu J. and others. (2006). CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat.Med. 12: 671-676.
938. Siegmund, S. V. and Schwabe, R. F. (2008). Endocannabinoids and liver disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis. Am.J.Physiol Gastrointest.Liver Physiol. 294: G357-G362.
939. Mallat, A., Hezode, C., and Lotersztajn, S. (2008). Environmental factors as disease accelerators during chronic hepatitis C. J.Hepatol. 48: 657-665.
940. Guy, G. W. and Stott, C. G. The development of Sativex®– a natural cannabis-based medicine. Cannabinoids as Therapeutics. Mechoulam, R. Basel: Birkhäuser Verlag, 2005.
941. Bolla, K. I., Brown, K., Eldreth, D., Tate, K. and others. (2002). Dose-related neurocognitive effects of marijuana use. Neurology. 59: 1337-1343.
942. Rubino, T. and Parolaro, D. (2008). Long lasting consequences of cannabis exposure in adolescence. Mol.Cell Endocrinol. 286: S108-S113.
943. Heishman, S. J., Stitzer, M. L., and Yingling, J. E. (1989). Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance. Pharmacol.Biochem.Behav. 34: 173-179.
944. Wetzel, C. D., Janowsky, D. S., and Clopton, P. L. (1982). Remote memory during marijuana intoxication. Psychopharmacology (Berl). 76: 278-281.
945. Fletcher, J. M., Page, J. B., Francis, D. J., Copeland, K. and others. (1996). Cognitive correlates of long-term cannabis use in Costa Rican men. Arch.Gen Psychiatry. 53: 1051-1057.
946. Pope, H. G., Jr., Gruber, A. J., Hudson, J. I., Cohane, G. and others. (2003). Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend. 69: 303-310.
947. Messinis, L., Kyprianidou, A., Malefaki, S., and Papathanasopoulos, P. (2006). Neuropsychological deficits in longterm frequent cannabis users. Neurology. 66: 737-739.
948. Lyketsos, C. G., Garrett, E., Liang, K. Y., and Anthony, J. C. (1999). Cannabis use and cognitive decline in persons under 65 years of age. Am.J.Epidemiol. 149: 794-800.
949. Pope, H. G., Jr., Gruber, A. J., Hudson, J. I., Huestis, M. A. and others. (2001). Neuropsychological performance in long-term cannabis users. Arch.Gen Psychiatry. 58: 909-915.
950. Pope, H. G., Jr., Gruber, A. J., and Yurgelun-Todd, D. (1995). The residual neuropsychological effects of cannabis: the current status of research. Drug Alcohol Depend. 38: 25-34.
951. Gonzalez, R., Carey, C., and Grant, I. (2002). Nonacute (residual) neuropsychological effects of cannabis use: a qualitative analysis and systematic review. J.Clin.Pharmacol. 42: 48S-57S.
952. Meier, M. H., Caspi, A., Ambler, A., Harrington, H. and others. (2012). Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc.Natl.Acad.Sci.U.S.A. 109: E2657-E2664.
953. Menetrey, A., Augsburger, M., Favrat, B., Pin, M. A. and others. (2005). Assessment of driving capability through the use of clinical and psychomotor tests in relation to blood cannabinoids levels following oral administration of 20 mg dronabinol or of a cannabis decoction made with 20 or 60 mg Delta9-THC. J.Anal.Toxicol. 29: 327-338.
954. Asbridge, M., Poulin, C., and Donato, A. (2005). Motor vehicle collision risk and driving under the influence of cannabis: evidence from adolescents in Atlantic Canada. Accid.Anal.Prev. 37: 1025-1034.
955. Gieringer, D. H. (1988). Marijuana, driving, and accident safety. J.Psychoactive Drugs. 20: 93-101.
956. Sexton, B. F., Tunbridge, R. J., Brook-Carter, N., Jackson, P. G. and others. The influence of cannabis on driving. (2007). 477. Berkshire, UK: TRL Limited.
957. Moskowitz, H. (1985). Marihuana and driving. Accid.Anal.Prev. 17: 323-345.
958. Bosker, W. M., Kuypers, K. P., Theunissen, E. L., Surinx, A. and others. (2012). Medicinal Delta(9) tetrahydrocannabinol (dronabinol) impairs on-the-road driving performance of occasional and heavy cannabis users but is not detected in Standard Field Sobriety Tests. Addiction. 107: 1837-1844.
959. Kuypers, K. P., Legrand, S. A., Ramaekers, J. G., and Verstraete, A. G. (2012). A case-control study estimating accident risk for alcohol, medicines and illegal drugs. PLoS.One. 7: e43496-
960. Laumon, B., Gadegbeku, B., Martin, J. L., and Biecheler, M. B. (2005). Cannabis intoxication and fatal road crashes in France: population based case-control study. BMJ. 331: 1371-
961. Khiabani, H. Z., Bramness, J. G., Bjorneboe, A., and Morland, J. (2006). Relationship between THC concentration in blood and impairment in apprehended drivers. Traffic.Inj.Prev. 7: 111-116.
962. Thornicroft, G. (1990). Cannabis and psychosis. Is there epidemiological evidence for an association? Br.J.Psychiatry. 157: 25-33.
963. Morrison, P. D., Zois, V., McKeown, D. A., Lee, T. D. and others. (2009). The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol.Med. 39: 1607-1616.
964. Kotin, J., Post, R. M., and Goodwin, F. K. (1973). 9 -Tetrahydrocannabinol in depressed patients. Arch.Gen.Psychiatry. 28: 345-348.
965. Ablon, S. L. and Goodwin, F. K. (1974). High frequency of dysphoric reactions to tetrahydrocannabinol among depressed patients. Am.J.Psychiatry. 131: 448-453.
966. Glass, R. M., Uhlenhuth, E. H., Hartel, F. W., Schuster, C. R. and others. (1980). A single dose study of nabilone, a synthetic cannabinoid. Psychopharmacology (Berl). 71: 137-142.
967. Glass, R. M., Uhlenhuth, E. H., Hartel, F. W., Schuster, C. R. and others. (1981). Single-dose study of nabilone in anxious volunteers. J.Clin.Pharmacol. 21: 383S-396S.
968. Degenhardt, L., Hall, W., and Lynskey, M. (2003). Exploring the association between cannabis use and depression. Addiction. 98: 1493-1504.
969. Harder, V. S., Morral, A. R., and Arkes, J. (2006). Marijuana use and depression among adults: Testing for causal associations. Addiction. 101: 1463-1472.
970. Harder, V. S., Stuart, E. A., and Anthony, J. C. (2008). Adolescent cannabis problems and young adult depression: male-female stratified propensity score analyses. Am.J.Epidemiol. 168: 592-601.
971. Stinson, F. S., Ruan, W. J., Pickering, R., and Grant, B. F. (2006). Cannabis use disorders in the USA: prevalence, correlates and co-morbidity. Psychol.Med. 36: 1447-1460.
972. van Laar, M., van Dorsselaer, S., Monshouwer, K., and de Graaf, R. (2007). Does cannabis use predict the first incidence of mood and anxiety disorders in the adult population? Addiction. 102: 1251-1260.
973. Chabrol, H., Chauchard, E., and Girabet, J. (2008). Cannabis use and suicidal behaviours in high-school students. Addict.Behav. 33: 152-155.
974. Pedersen, W. (2008). Does cannabis use lead to depression and suicidal behaviours? A population-based longitudinal study. Acta Psychiatr.Scand. 118: 395-403.
975. Henquet, C., Krabbendam, L., de, Graaf R., ten, Have M. and others. (2006). Cannabis use and expression of mania in the general population. J.Affect.Disord. 95: 103-110.
976. Strakowski, S. M., DelBello, M. P., Fleck, D. E., Adler, C. M. and others. (2007). Effects of co-occurring cannabis use disorders on the course of bipolar disorder after a first hospitalization for mania. Arch.Gen.Psychiatry. 64: 57-64.
977. Agrawal, A., Nurnberger, J. I., Jr., and Lynskey, M. T. (2011). Cannabis involvement in individuals with bipolar disorder. Psychiatry Res. 185: 459-461.
978. De Pradier, M., Gorwood, P., Beaufils, B., Ades, J. and others. (2010). Influence of the serotonin transporter gene polymorphism, cannabis and childhood sexual abuse on phenotype of bipolar disorder: a preliminary study. Eur.Psychiatry. 25: 323-327.
979. Baethge, C., Hennen, J., Khalsa, H. M., Salvatore, P. and others. (2008). Sequencing of substance use and affective morbidity in 166 first-episode bipolar I disorder patients. Bipolar.Disord. 10: 738-741.
980. Martinez-Gras, I., Hoenicka, J., Ponce, G., Rodriguez-Jimenez, R. and others. (2006). (AAT)n repeat in the cannabinoid receptor gene, CNR1: association with schizophrenia in a Spanish population. Eur.Arch.Psychiatry Clin.Neurosci. 256: 437-441.
981. Monteleone, P., Bifulco, M., Maina, G., Tortorella, A. and others. (2010). Investigation of CNR1 and FAAH endocannabinoid gene polymorphisms in bipolar disorder and major depression. Pharmacol.Res. 61: 400404.
982. Lagerberg, T. V., Sundet, K., Aminoff, S. R., Berg, A. O. and others. (2011). Excessive cannabis use is associated with earlier age at onset in bipolar disorder. Eur.Arch.Psychiatry Clin.Neurosci. 261: 397-405.
983. Braga, R. J., Burdick, K. E., Derosse, P., and Malhotra, A. K. (2012). Cognitive and clinical outcomes associated with cannabis use in patients with bipolar I disorder. Psychiatry Res. 200: 242-245.
984. Allebeck, P. Cannabis and psychiatric syndrome. Marihuana and medicine. Nahas, C. G., Sutin, K. M., Harvey, D. J., and Agurell, S. Totowa, New Jersey: Humana Press, 1999.
985. Caspari, D. (1999). Cannabis and schizophrenia: results of a follow-up study. Eur.Arch.Psychiatry Clin.Neurosci. 249: 45-49.
986. Zammit, S., Allebeck, P., Andreasson, S., Lundberg, I. and others. (2002). Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ. 325: 1199-1203.
987. Arseneault, L., Cannon, M., Poulton, R., Murray, R. and others. (2002). Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ. 325: 1212-1213.
988. Arseneault, L., Cannon, M., Witton, J., and Murray, R. M. (2004). Causal association between cannabis and psychosis: examination of the evidence. Br.J.Psychiatry. 184: 110-117.
989. Decoster, J., van, Os J., Kenis, G., Henquet, C. and others. (2011). Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction. Am.J.Med.Genet.B Neuropsychiatr.Genet. 156B: 363-369.
990. Tunbridge, E. M., Harrison, P. J., and Weinberger, D. R. (2006). Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biol.Psychiatry. 60: 141-151.
991. McIntosh, A. M., Baig, B. J., Hall, J., Job, D. and others. (2007). Relationship of catechol-O-methyltransferase variants to brain structure and function in a population at high risk of psychosis. Biol.Psychiatry. 61: 11271134.
992. Miyake, N., Thompson, J., Skinbjerg, M., and Abi-Dargham, A. (2011). Presynaptic dopamine in schizophrenia. CNS.Neurosci.Ther. 17: 104-109.
993. Fan, J. B., Zhang, C. S., Gu, N. F., Li, X. W. and others. (2005). Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biol.Psychiatry. 57: 139-144.
994. Ayalew, M., Le-Niculescu, H., Levey, D. F., Jain, N. and others. (2012). Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction. Mol.Psychiatry. 17: 887-905.
995. D’Souza, D. C., Sewell, R. A., and Ranganathan, M. (2009). Cannabis and psychosis/schizophrenia: human studies. Eur.Arch.Psychiatry Clin.Neurosci. 259: 413-431.
996. Castle, D. J. and Solowij, N. Acute and subacute psychomimetic effects of cannabis in humans. Marijuana and madness. Castle, D. and Murray, R. Cambridge: Cambridge University Press, 2004.
997. Fridberg, D. J., Vollmer, J. M., O’Donnell, B. F., and Skosnik, P. D. (2011). Cannabis users differ from non-users on measures of personality and schizotypy. Psychiatry Res. 186: 46-52.
998. Thompson, G. R., Rosenkrantz, H., Schaeppi, U. H., and Braude, M. C. (1973). Comparison of acute oral toxicity of cannabinoids in rats, dogs and monkeys. Toxicol.Appl.Pharmacol. 25: 363-372.
999. Robson, P. (2001). Therapeutic aspects of cannabis and cannabinoids. Br.J.Psychiatry. 178: 107-115.
1000. Weinstein, A. M. and Gorelick, D. A. (2011). Pharmacological treatment of cannabis dependence. Curr.Pharm.Des. 17: 1351-1358.