Evidence for the involvement of cannabinoid receptors' polymorphisms in the pathophysiology of human diseases

Expert Opinion on Therapeutic Targets

Volumn 17, Issue 4, 2013, Pages 363-377

  Vasileiou, Ioanna ^a   Fotopoulou, Georgia ^a   Matzourani, Marina ^a   Patsouris, Efstratios ^a   Theocharis, Stamatios ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

Author keywords

Behavioral disorders; Cannabinoid receptors; Endocannabinoid system; Obesity; Polymorphisms

Indexed keywords

ALCOHOL; CANNABINOID; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; CANNABIS; COCAINE; DEXTRAN SULFATE; MESSENGER RNA; NICOTINE;

3' UNTRANSLATED REGION; ALCOHOLISM; ALLELE; ANOREXIA NERVOSA; ANTIINFLAMMATORY ACTIVITY; ANXIETY DISORDER; ATHEROSCLEROSIS; ATTENTION DEFICIT DISORDER; BEHAVIOR DISORDER; BIPOLAR DISORDER; BODY MASS; BODY WEIGHT; BONE DENSITY; BULIMIA; CARDIOVASCULAR RISK; CHILDHOOD OBESITY; COCAINE DEPENDENCE; COLITIS; CROHN DISEASE; DELIRIUM TREMENS; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; DNA FLANKING REGION; DRUG DEPENDENCE; EATING DISORDER; ENTERITIS; GENE FREQUENCY; GENETIC POLYMORPHISM; HAPLOTYPE; HEBEPHRENIA; HOMOZYGOTE; HUMAN; IRRITABLE COLON; LOW DRUG DOSE; MAJOR DEPRESSION; METABOLIC SYNDROME X; MIGRAINE; MULTIPLE SCLEROSIS; NIDATION; NONHUMAN; OBESITY; PARKINSON DISEASE; PATHOPHYSIOLOGY; POSTTRAUMATIC STRESS DISORDER; PROMOTER REGION; RECEPTOR GENE; REVIEW; SCHIZOPHRENIA; SYSTEMIC DISEASE; TOBACCO DEPENDENCE; TRINUCLEOTIDE REPEAT; ULCERATIVE COLITIS; WITHDRAWAL SYNDROME;

ANIMALS; AUTOIMMUNE DISEASES; GENETIC ASSOCIATION STUDIES; HUMANS; MENTAL DISORDERS; MIGRAINE DISORDERS; OBESITY; OSTEOPOROSIS; POLYMORPHISM, GENETIC; RECEPTORS, CANNABINOID; SUBSTANCE-RELATED DISORDERS;

EID: 84875131825     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2013.754426     Document Type: Review

References (122)

1. Mechoulam R, Gaoni Y. A total synthesis of DL-Delta-1- Tetrahydrocannabinol, the active constituent of hashish. J Am Chem Soc 1965;20:32735
2. Johnson KM, Dewey WL, Harris LS. Some structural requirement for inhibition of high-affinity synaptosomal serotonin uptake by cannabinoids. Mol Pharmacol 1976;12:345-52
3. Norrod AG, Puffenbarger RA. Genetic polymorphisms of the endocannabinoid system. Chem Biodivers 2007;4:1926-32
4. Rodriguez de Fonseca F, Del Arco I, Bermudez-Silva FJ, et al. The endocannabinoid system: Physiology and pharmacology. Alcohol 2005;40:2-14
5. Matsuda LA, Lolait TI, Brownstein M, et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990;346:561-4
6. Howlett AC, Mukhopadhyay S. Cellular signal transduction by anandamide and 2-arachidonoylglycerol. Chem Phys Lipids 2000;108:53-70
7. Guzman M, Galve-Roperh I, Sanchez C. Ceramide; a new second messenger of cannabinoid action. Trends Pharmacol Sci 2001;22:19-22
8. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258:1946-9
9. Pertwee RG, Ross RA. Cannabinoid receptors and their ligands. Prostaglandins Leukot Essent Fatty Acids 2002;66:101-21
10. Bisogno T. Endogenous cannabinoids: Structure and metabolism. J Neuroendocrinol 2008;20(Suppl 1):1-9
11. Bari M, Battista N, Fezza F, et al. New insights into endocannabinoid degradation and its therapeutic potential. Mini Rev Med Chem 2006;6:257-68
12. Gerard CM, Mollereau C, Vassart G, et al. Molecular cloning of a human cannabinoid receptor which is also expressed in the testis. Biochem J 1991;279:129-34
13. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993;365:61-5
14. Shire D, Calandra B, Bouaboula M, et al. Cannabinoid receptor interactions with the antagonists SR 141716A and SR 144528. Life Sci 1999;65:627-35
15. Onaivi ES, Leonard CM, Ishiquro H, et al. Endocannabinoids and cannabinoid receptor genetics. Prog Neurobiol 2002;66:307-44
16. Onaivi ES. Neuropsychobiological evidence for the functional presence and expression of cannabinoid CB2 receptors in the brain. Neuropsychobiology 2006;54:231-46
17. Berdyshev EV. Cannabinoid receptors and the regulation of immune response. Chem Phys Lipids 2000;108:169-90
18. Gong JP, Onaivi ES, Ishiquro H, et al. Cannabinoid CB2 receptors: Immunohistochemical localization in rat brain. Brain Res 2006;1071:10-23
19. McPartland JM, Norris RW, Kilpatrick CW. Tempo and mode in the endocannabinoid system. J Mol Evol 2007;65:267-76
20. Liu J, Wang L, Harvey-White J, et al. A biosynthetic pathway for anandamide. Proc Natl Acad Sci 2006;103:13345-50
21. Wilson RI, Nicoll RA. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 2001;410:588-92
22. Hampson RE, Evans JG, Mu J, et al. Role of cyclic AMP dependent protein kinase in cannabinoid receptor modulation of potassium "A-current" in cultured rat hippocampal neurons. Life Sci 1995;56:2081-8
23. Mackie K, Hillie B. Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci USA 1992;89:3825-9
24. Ueda N, Kurahashi Y, Yamamoto S, et al. Partial purification and characterization of the porcine brain enzyme hydrolyzing and synthesizing anandamide. J Biol Chem 1995;270:23823-7
25. Tsuboi K, Sun YX, Okamoto Y, et al. Molecular characterization of N-acylethanolamine -hydrolazing acid amidase, a novel member of the choloylglycine hydrolase family with structural and functional similarity to acid ceramidase. J Biol Chem 2005;280:11082-92
26. Dinh TP, Carpenter D, Lesile FM, et al. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 2002;99:10819-24
27. McFarland MJ, Barker EL. Anandamide transport. Pharmacol Ther 2004;104:117-35
28. Hillard CJ, Jarrahian A. Cellular accumulation of anandamide: Consensus and controversy. Br J Pharmacol 2003;140:802-8
29. Bab I, Zimmer A. Cannabinoid receptors and the regulation of bone mass. Br J Pharmacol 2008;153:182-8
30. Klump KL, Kaye WH, Strober M. The evolving genetic foundations of eating disorders. Psychiatr Clin North Am 2001;24:215-25
31. Berry EM, Mechoulam R. Tetrahydrocannabinol endocannabinoids in feeding and appetite. Pharmacol Ther 2002;95:185-90
32. Cota D, Tschop MH, Horvath TL, et al. Cannabinoids, opioids and eating behaviour: The molecular face of hedonism. Brain Res Rev 2006;51:85-107
33. Siegfield Z, Kanyas K, Latzer Y, et al. Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: Differences between restricting and bingeing/purging subtypes. Am J Med Genet B Neuropsychiatr Genet 2004;125B:126-30
34. Arias F, Ampuero I, Saqredo O, et al. Lack of association between polymorphisms in cannabinoid receptor gene (CNR1) and fatty acid amide hydroxylase gene (FAAH) and eating disorders in a preliminary study. Phychiatric Genet 2009;19:336
35. Schroth GP, Chou PJ, Ho PS. Mapping Z-DNA in the human genome. Computer-aided mapping reveals a nonrandom distribution of potential Z-DNA-forming sequences in human genes. J Biol Chem 1992;267:11846-55
36. Monteleone P, Bifulco M, Di Filippo C, et al. Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: Evidence for synergistic effects. Genes Brain Behav 2009;8:728-32
37. Estourgie-van Burk GF, Bartels M, van Beijsterveldt TC, et al. Body size in five-year-old twins: Heritability and comparison to singleton standards. Twin Res Hum Genet 2006;9:646-55
38. Fox CS, Heard-Costa NL, Vasan RS, et al. Framingham Heart Study. Genomewide linkage analysis of weight change in the Framingham Heart Study. J Clin Endocrinol Metab 2005;90:3197-201
39. Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral and subcutaneous adipose tissue compartments: Association with metabolic risk factors in the Framingham Heart Study. Circulation 2007;116:39-48
40. Di Marzo V, Petrosino S. Endocannabinoids and the regulation of their levels in health and disease. Curr Opin Lipidol 2007;18:129-40
41. Cota D Role of the endocannabinoid system in energy balance regulation and obesity. Front Horm Res 2008;36:135-45
42. Eggan SM, Lewis DA. Immunocytochemical distribution of the cannabinoid receptor CB1 in the primate neocortex: A regional and laminar analysis. Cereb Cortex 2007;17:175-91
43. Jbilo O, Ravinet-Trilou C, Arnone M, et al. The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. FASEB J 2005;19:1567-9
44. Pagano C, Pilon C, Calcaqno A, et al. The endogenous cannabinoid system stimulates glucose uptake in human fat cells via phosphatidylinositol 3-kinase and calcium-dependent mechanisms. J Clin Endocrinol Metab 2007;92:4810-19
45. Baye TM, Zhang Y, Smith E, et al. Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index. Pharmacogenomics 2008;9:1647-56
46. Bordicchia M, Battistoni I, Mancinelli L, et al. CB1 receptor expression in relation to visceral adipose depots, endocannabinoid levels, microvascular damage, and the presence of the Cnr1 A3813G variant in humans. Metabolism 2010;59:734-41
47. Russo P, Strazzullo P, Cappuccio FP, et al. Genetic variations at the endocannabinoid type 1 receptor gene (CNR1) are associated with obesity phenotypes in men. J Clin Endocrinol Metab 2007;92:2382-6
48. Jaeger JP, Mattevi VS, Callegari-Jacques SM, et al. Cannabinoid type-1 receptor gene polymorphisms are associated with central obesity in a Southern Brazilian population. Dis Markers 2008;25:67-74
49. Hu WC, Feng P. G1359A polymorphism in the cannabinoid receptor-1 gene is associated with metabolic syndrome in the Chinese Han population. Arch Med Res 2010;41:378-82
50. Muller TD, Reichwald K, Wermter AK, et al. No evidence for an involvement of variants in the cannabinoid receptor gene (CNR1) in obesity in German children and adolescents. Mol Genet Metab 2007;90:429-34
51. Aberle J, Fedderwitz I, Klages N, et al. Genetic variation in two proteins of the endocannabinoid system and their influence on body mass index and metabolism under low fat diet. Horm Metab Res 2007;39:395-3977
52. de Luis DA, Gonzalez Sagrado M, Aller R, et al. Influence of G1359A polymorphism of the cannabinoid receptor gene on anthropometric parameters and insulin resistance in women with obesity. Metabolism 2011;60:272-6
53. Benzinou M, Chevre JC, Ward KJ, et al. Endocannabinoid receptor 1 gene variations increase risk for obesity and modulate body mass index in European populations. Hum Mol Genet 2008;17:1916-21
54. Monteleone P, Milano W, Petrella C, et al. Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. J Clin Psychopharmacol 2010;30:441-5
55. Martin M, Ledent C, Parmentier M, et al. Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology (Berl) 2002;159:379-87
56. Dinh TP, Carpenter D, Lesile FM, et al. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 2002;99:10819-24
57. McFarland MJ, Barker EL. Anandamide transport. Pharmacol Ther 2004;104:117-35
58. Hillard CJ, Jarrahian A. Cellular accumulation of anandamide: Consensus and controversy. Br J Pharmacol 2003;140:802-8
59. Bab I, Zimmer A. Cannabinoid receptors and the regulation of bone mass. Br J Pharmacol 2008;153:182-8
60. Klump KL, Kaye WH, Strober M. The evolving genetic foundations of eating disorders. Psychiatr Clin North Am 2001;24:215-25
61. Berry EM, Mechoulam R. Tetrahydrocannabinol endocannabinoids in feeding and appetite. Pharmacol Ther 2002;95:185-90
62. Cota D, Tschop MH, Horvath TL, et al. Cannabinoids, opioids and eating behaviour: The molecular face of hedonism. Brain Res Rev 2006;51:85-107
63. Siegfield Z, Kanyas K, Latzer Y, et al. Association study of cannabinoid receptor gene (CNR1) alleles and anorexia nervosa: Differences between restricting and bingeing/purging subtypes. Am J Med Genet B Neuropsychiatr Genet 2004;125B:126-30
64. Arias F, Ampuero I, Saqredo O, et al. Lack of association between polymorphisms in cannabinoid receptor gene (CNR1) and fatty acid amide hydroxylase gene (FAAH) and eating disorders in a preliminary study. Phychiatric Genet 2009;19:336
65. Schroth GP, Chou PJ, Ho PS. Mapping Z-DNA in the human genome. Computer-aided mapping reveals a nonrandom distribution of potential Z-DNA-forming sequences in human genes. J Biol Chem 1992;267:11846-55
66. Monteleone P, Bifulco M, Di Filippo C, et al. Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: Evidence for synergistic effects. Genes Brain Behav 2009;8:728-32
67. Estourgie-van Burk GF, Bartels M, van Beijsterveldt TC, et al. Body size in five-year-old twins: Heritability and comparison to singleton standards. Twin Res Hum Genet 2006;9:646-55
68. Fox CS, Heard-Costa NL, Vasan RS, et al. Framingham Heart Study. Genomewide linkage analysis of weight change in the Framingham Heart Study. J Clin Endocrinol Metab 2005;90:3197-201
69. Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral and subcutaneous adipose tissue compartments: Association with metabolic risk factors in the Framingham Heart Study. Circulation 2007;116:39-48
70. Di Marzo V, Petrosino S. Endocannabinoids and the regulation of their levels in health and disease. Curr Opin Lipidol 2007;18:129-40
71. Cota D Role of the endocannabinoid system in energy balance regulation and obesity. Front Horm Res 2008;36:135-45
72. Eggan SM, Lewis DA. Immunocytochemical distribution of the cannabinoid receptor CB1 in the primate neocortex: A regional and laminar analysis. Cereb Cortex 2007;17:175-91
73. Jbilo O, Ravinet-Trilou C, Arnone M, et al. The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. FASEB J 2005;19:1567-9
74. Pagano C, Pilon C, Calcaqno A, et al. The endogenous cannabinoid system stimulates glucose uptake in human fat cells via phosphatidylinositol 3-kinase and calcium-dependent mechanisms. J Clin Endocrinol Metab 2007;92:4810-19
75. Baye TM, Zhang Y, Smith E, et al. Genetic variation in cannabinoid receptor 1 (CNR1) is associated with derangements in lipid homeostasis, independent of body mass index. Pharmacogenomics 2008;9:1647-56
76. Bordicchia M, Battistoni I, Mancinelli L, et al. CB1 receptor expression in relation to visceral adipose depots, endocannabinoid levels, microvascular damage, and the presence of the Cnr1 A3813G variant in humans. Metabolism 2010;59:734-41
77. Russo P, Strazzullo P, Cappuccio FP, et al. Genetic variations at the endocannabinoid type 1 receptor gene (CNR1) are associated with obesity phenotypes in men. J Clin Endocrinol Metab 2007;92:2382-6
78. Jaeger JP, Mattevi VS, Callegari-Jacques SM, et al. Cannabinoid type-1 receptor gene polymorphisms are associated with central obesity in a Southern Brazilian population. Dis Markers 2008;25:67-74
79. Hu WC, Feng P. G1359A polymorphism in the cannabinoid receptor-1 gene is associated with metabolic syndrome in the Chinese Han population. Arch Med Res 2010;41:378-82
80. Muller TD, Reichwald K, Wermter AK, et al. No evidence for an involvement of variants in the cannabinoid receptor gene (CNR1) in obesity in German children and adolescents. Mol Genet Metab 2007;90:429-34
81. Aberle J, Fedderwitz I, Klages N, et al. Genetic variation in two proteins of the endocannabinoid system and their influence on body mass index and metabolism under low fat diet. Horm Metab Res 2007;39:395-3977
82. de Luis DA, Gonzalez Sagrado M, Aller R, et al. Influence of G1359A polymorphism of the cannabinoid receptor gene on anthropometric parameters and insulin resistance in women with obesity. Metabolism 2011;60:272-6
83. Benzinou M, Chevre JC, Ward KJ, et al. Endocannabinoid receptor 1 gene variations increase risk for obesity and modulate body mass index in European populations. Hum Mol Genet 2008;17:1916-21
84. Monteleone P, Milano W, Petrella C, et al. Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. J Clin Psychopharmacol 2010;30:441-5
85. Martin M, Ledent C, Parmentier M, et al. Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology (Berl) 2002;159:379-87
86. Herman AI, Kranzler HR, Cubells JF, et al. Association study of the CNR1 gene exon 3 alternative promoter region polymorphisms and substance dependence. Am J Med Genet B Neuropsychiatr Genet 2006;141B:499-503
87. Agrawal A, Wetherill L, Dick DM, et al. Evidence for association between polymorphisms in the cannabinoid receptor 1 (CNR1) gene and cannabis dependence. Am J Med Genet B Neuropsychiatr Genet 2009;150B:736-40
88. Hopfer CJ, Young SE, Purcell S, et al. Cannabis receptor haplotype associated with fewer cannabis dependence symptoms in adolescents. Am J Med Genet B Neuropsychiatr Genet 2006;141B:895-901
89. Hartman CA, Hopfer CJ, Haberstick B, et al. The association between cannabinoid receptor 1 gene (CNR1) and cannabis dependence symptoms in adolescents and young adults. Drug Alcohol Depend 2009;104:11-16
90. Johnson JP, Muhleman D, McMurray J, et al. Association between the cannabinoid receptor gene (CNR1) and the P300 event-related potential. Mol Psychiatry 1997;2:169-71
91. Ballon N, Leroy S, Roy C, et al. (AAT) repeat in the cannabinoid receptor gene (CNR1): Association with cocaine addiction in an African-Caribbean population. Pharmacogenomics 2006;6:126-30
92. Benyamina A, Kebir O, Blecha L, et al. CNR1 gene polymorphisms in addictive disorders: A systematic review and a meta-analysis. Addict Biol 2011;16:1-6
93. Haughey HM, Marshall E, Schacht JP, et al. Marijuana withdrawal and craving: Influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes. Addiction 2008;103:1678-86
94. Filbey FM, Schacht JP, Myers US, et al. Individual and additive effects of the CNR1 and FAAH genes on brain response to marijuana cues. Neuropsychopharmacology 2010;35:967-75
95. Chen X, Williamson WS, An SS, et al. Cannabinoid receptor 1 gene association with nicotine dependence. Arch Gen Psychiatry 2008;65:816-24
96. Esfandyari T, Cammileri M, Busciqlio I, et al. 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 2007;293:137-45
97. Massa F, Storr M, Lutz B. The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J Mol Med 2005;83:944-54
98. Kimball ES, Schneider CR, Wallace NH, et al. 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 2006;291:G364-71
99. Massa F, Marsicano G, Hermann H, et al. Endogenous cannabinoid system protects against colonic inflammation. J Clin Invest 2004;113:1202-9
100. Storr M, Emmerdinger D, Diegelmann J, et al. The cannabinoid 1 receptor (CNR1) 1359 G/A polymorphism modulates susceptibility to ulcerative colitis and the phenotype in Crohn's disease. PLoS One 2010;5:e9453
101. Storr MA, Keenan CM, Emmerdinger D, et al. Targeting endocannabinoid degradation protects against experimental colitis in mice: Involvement of CB1 and CB2 receptors. J Mol Med 2008;86:925-36
102. Park JM, Choi M, Cho YK, et al. Cannabinoid receptor 1 gene polymorphism and irritable bowel syndrome in the Korean population: A hypothesis-generating study. J Clin Gastroenterol 2011;45:45-9
103. Siegmund SV, Schwabe RF. Endocannabinoids and liver disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2008;294:357-62
104. Akerman S, Holland PR, Goadsby PJ. Cannabinoid (CB1) receptor activation inhibits trigeminovascular neurons. J Pharmacol Exp Ther 2007;320:64-71
105. Akerman S, Kaube H, Goadsby PJ. Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception. J Pharmacol Exp Ther 2004;309:56-63
106. Juhasz G, Lazary J, Chase D, et al. Variations in the cannabinoid receptor 1 gene predispose to migraine. Neurosci Lett 2009;461:116-20
107. Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: Results from the National Comorbidity Survey Replication. Am J Psychiatry 2006;163(4):716-23
108. McGough JJ, Smalley SL, McCracken JT, et al. Psychiatric comorbidity in adult attention deficit hyperactivity disorder: Findings from multiplex families. Am J Psychiatry 2005;162:1621-7
109. Woolmore J, Stone M, Holey S, et al. Polymorphisms of the cannabinoid 1 receptor gene and cognitive impairment in multiple sclerosis. Mult Scler 2008;14:177-82
110. Rossi S, Buttari F, Studer V, et al. The (AAT)n repeat of the cannabinoid CB1 receptor gene influences disease progression in relapsing multiple sclerosis. Mult Scler 2011;17:281-8.
111. Tam J, Trembovler V, Di Marzo V, et al. The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling. FASEB J 2008;22:285-94
112. Bab I, Zimmer A, Melamed E. Cannabinoids and the skeleton: From marijuana to reversal of bone loss. Ann Med 2009;41:560-7
113. Huang QY, Li GH, Kung AW. Multiple osteoporosis susceptibility genes on chromosome 1p36 in Chinese 2009. Bone 44:984-8
114. Karsak M, Cohen-Solal M, Freudenberg J, et al. Cannabinoid receptor type 2 gene is associated with human osteoporosis. Hum Mol Genet 2005;14:3389-96
115. Yamada Y, Ando F, Shimokata H. Association of candidate gene polymorphisms with bone mineral density in community-dwelling Japanese women and men. Int J Mol Med 2007;19:791-801
116. Karsak M, Malkin I, Toliat MR, et al. The cannabinoid receptor type 2 (CNR2) gene is associated with hand bone strength phenotypes in an ethnically homogeneous family sample. Hum Genet 2009;126:629-36
117. Steffens S, Veillard NL, Arnaud C, et al. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature 2005;434:782-6
118. Reinhard W, Stark K, Neurether K, et al. Common polymorphisms in the cannabinoid CB2 receptor gene (CNR2) are not associated with myocardial infarction and cardiovascular risk factors. Int J Mol Med 2008;22:165-74
119. Wang H, Guo Y, Wang D, et al. Aberrant cannabinoid signaling impairs oviductal transport of embryos. Nat Med 2004;10:1074-80
120. Paria BC, Dey SK. Ligand-receptor signaling with endocannabinoids in preimplantation embryo development and implantation. Chem Phys Lipids 2000;108:211-20
121. Paria BC, Song H, Wuang X, et al. Dysregulated cannabinoid signaling disrupts uterine receptivity for embryo implantation. J Biol Chem 2001;276:20523-8
122. Horne AW, Phillips AJ III, Kane N, et al. CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic pregnancy. PLoS One 2008;3:e3969