CB1 and CB2 receptors are influenced via exogenous and endogenous cannabinoids. To date, little is known regarding changes in receptor expression and methylation in THC (tetrahydrocannabinol) dependence. Therefore, the CB1 and CB2 receptor mRNA expression levels and promoter methylation status in the peripheral blood cells of 77 subjects (36 with THC dependence, 21 cigarette smokers and 20 nonsmokers) were assessed by quantitative real-time PCR and methylation-specific PCR. There was a significant difference in CB1 receptor expression levels between the three groups (ANOVA, p < 0.001, d.f. = 2, F = 71.3). The mean promoter methylation (%) was significantly negatively correlated with CB1 receptor mRNA expression levels (Spearman’s rho: r = –0.37; p = 0.002). Using a mixed general linear model, it was demonstrated that the CB1 mRNA expression (as the dependent variable) was associated with the satisfaction with life scale (SWLS) (r = 0.101; T = 2.8; p = 0.007), craving (as measured with the VAS; r = –0.023; T = –2.3; p = 0.023) and the WHO-Assist Subscale for Cannabis consumption (r = –0.068; T = –2.4; p = 0.02). CB1 receptor expression levels and methylation status appear to be altered in subjects with THC dependence.

1.
Cooper ZD, Haney M: Cannabis reinforcement and dependence: role of the cannabinoid cb1 receptor. Addict Biol 2008;13:188–195.
2.
Noack R, Hofler M, Lueken U: Cannabis use patterns and their association with dsm-iv cannabis dependence and gender. Eur Addict Res 2011;17:321–328.
3.
Compton WM, Grant BF, Colliver JD, Glantz MD, Stinson FS: Prevalence of marijuana use disorders in the United States: 1991–1992 and 2001–2002. JAMA 2004;291:2114–2121.
4.
Shapiro GK, Buckley-Hunter L: What every adolescent needs to know: cannabis can cause psychosis. J Psychosom Res 2010;69:533–539.
5.
Agosti V, Nunes E, Levin F: Rates of psychiatric comorbidity among US residents with lifetime cannabis dependence. Am J Drug Alcohol Abuse 2002;28:643–652.
6.
Iversen L: Cannabis and the brain. Brain 2003;126:1252–1270.
7.
Bab I, Zimmer A, Melamed E: Cannabinoids and the skeleton: from marijuana to reversal of bone loss. Ann Med 2009;41:560–567.
8.
Howlett AC: The cannabinoid receptors. Prostaglandins Other Lipid Mediat 2002;68–69:619–631.
9.
Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, Porrino LJ: Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 2004;47(suppl 1):345–358.
10.
Green B, Kavanagh D, Young R: Being stoned: a review of self-reported cannabis effects. Drug Alcohol Rev 2003;22:453–460.
11.
Hall W, Degenhardt L: Adverse health effects of non-medical cannabis use. Lancet 2009;374:1383–1391.
12.
Agrawal A, Lynskey MT: The genetic epidemiology of cannabis use, abuse and dependence. Addiction 2006;101:801–812.
13.
Agrawal A, Lynskey MT: Candidate genes for cannabis use disorders: findings, challenges and directions. Addiction 2009;104:518–532.
14.
McClung CA, Nestler EJ: Neuroplasticity mediated by altered gene expression. Neuropsychopharmacology 2008;33:3–17.
15.
Rodenhiser D, Mann M: Epigenetics and human disease: translating basic biology into clinical applications. CMAJ 2006;174:341–348.
16.
Parmentier-Batteur S, Jin K, Xie L, Mao XO, Greenberg DA: DNA microarray analysis of cannabinoid signaling in mouse brain in vivo. Mol Pharmacol 2002;62:828–835.
17.
Henquet C, Di Forti M, Morrison P, Kuepper R, Murray RM: Gene-environment interplay between cannabis and psychosis. Schizophr Bull 2008;34:1111–1121.
18.
Ehrlich S, Walton E, Roffman JL, Weiss D, Puls I, Doehler N, Burghardt R, Lehmkuhl U, Hillemacher T, Muschler M, Frieling H: Smoking, but not malnutrition, influences promoter-specific DNA methylation of the proopiomelanocortin gene in patients with and without anorexia nervosa. Can J Psychiatry 2012;57:168–176.
19.
Derogatis LR, Rickels K, Rock AF: The Scl-90 and the MMPI: a step in the validation of a new self-report scale. Br J Psychiatry 1976;128:280–289.
20.
Diener E, Emmons RA, Larsen RJ, Griffin S: The satisfaction with life scale. J Pers Assess 1985;49:71–75.
21.
Group WAW: The alcohol, smoking and substance involvement screening test (Assist): Development, reliability and feasibility. Addiction 2002;97:1183–1194.
22.
Fagerstrom KO: Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addict Behav 1978;3:235–241.
23.
Bleich S, Carl M, Bayerlein K, Reulbach U, Biermann T, Hillemacher T, Bonsch D, Kornhuber J: Evidence of increased homocysteine levels in alcoholism: the Franconian alcoholism research studies (FARS). Alcohol Clin Exp Res 2005;29:334–336.
24.
Bleich S, Lenz B, Ziegenbein M, Beutler S, Frieling H, Kornhuber J, Bonsch D: Epigenetic DNA hypermethylation of the HERP gene promoter induces down-regulation of its mRNA expression in patients with alcohol dependence. Alcohol Clin Exp Res 2006;30:587–591.
25.
Frieling H, Albrecht H, Jedtberg S, Gozner A, Lenz B, Wilhelm J, Hillemacher T, de Zwaan M, Kornhuber J, Bleich S: Elevated cannabinoid 1 receptor mRNA is linked to eating disorder related behavior and attitudes in females with eating disorders. Psychoneuroendocrinology 2009;34:620–624.
26.
Romero J, Garcia-Palomero E, Castro JG, Garcia-Gil L, Ramos JA, Fernandez-Ruiz JJ: Effects of chronic exposure to delta9-tetrahydrocannabinol on cannabinoid receptor binding and mRNA levels in several rat brain regions. Brain Res Mol Brain Res 1997;46:100–108.
27.
Cross SH, Bird AP: CPG islands and genes. Curr Opin Genet Dev 1995;5:309–314.
28.
Razin A, Riggs AD: DNA methylation and gene function. Science 1980;210:604–610.
29.
Callinan PA, Feinberg AP: The emerging science of epigenomics. Hum Mol Genet 2006;15:R95–R101.
30.
Zhang FF, Cardarelli R, Carroll J, Fulda KG, Kaur M, Gonzalez K, Vishwanatha JK, Santella RM, Morabia A: Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood. Epigenetics 2011;6:623–629.
31.
Haney M, Comer SD, Ward AS, Foltin RW, Fischman MW: Factors influencing marijuana self-administration by humans. Behav Pharmacol 1997;8:101–112.
32.
Cleland JG, Ghosh J, Freemantle N, Kaye GC, Nasir M, Clark AL, Coletta AP: Clinical trials update and cumulative meta-analyses from the American College of Cardiology: watch, scd-heft, dinamit, casino, inspire, stratus-us, rio-lipids and cardiac resynchronisation therapy in heart failure. Eur J Heart Fail 2004;6:501–508.
33.
Monshouwer K, Huizink AC, Harakeh Z, Raaijmakers QA, Reijneveld SA, Oldehinkel AJ, Verhulst FC, Vollebergh WA: Prenatal smoking exposure and the risk of behavioral problems and substance use in adolescence: the trails study. Eur Addict Res 2011;17:342–350.
34.
Mechoulam R, Parker L: Cannabis and alcohol – a close friendship. Trends Pharmacol Sci 2003;24:266–268.
35.
Mackie K: Cannabinoid receptors as therapeutic targets. Annu Rev Pharmacol Toxicol 2006;46:101–122.
36.
Lupica CR, Riegel AC: Endocannabinoid release from midbrain dopamine neurons: a potential substrate for cannabinoid receptor antagonist treatment of addiction. Neuropharmacology 2005;48:1105–1116.
37.
Sim-Selley LJ: Regulation of cannabinoid cb1 receptors in the central nervous system by chronic cannabinoids. Crit Rev Neurobiol 2003;15:91–119.
38.
Bayerlein K, Kraus T, Leinonen I, Pilniok D, Rotter A, Hofner B, Schwitulla J, Sperling W, Kornhuber J, Biermann T: Orexin A expression and promoter methylation in patients with alcohol dependence comparing acute and protracted withdrawal. Alcohol 2011;45:541–547.
39.
Lawrence AJ: Regulation of alcohol-seeking by orexin (hypocretin) neurons. Brain Res 2010;1314:124–129.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.