{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T21:12:46Z","timestamp":1783372366505,"version":"3.54.6"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,2,8]],"date-time":"2007-02-08T00:00:00Z","timestamp":1170892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt B"],"published-print":{"date-parts":[[2007,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A genetic variation in fatty acid amide hydrolase (FAAH), C385A (P129T), has been previously associated with risk for problem street drug use. FAAH is a mammalian enzyme that inactivates neuromodulatory\u2010signaling lipids including the endogenous cannabinoid 1 receptor agonist anandamide. We investigated in adult Caucasians (N\u2009=\u2009749) whether this FAAH variant altered the risk for trying, regular use of or dependence on cannabis, alcohol or nicotine, traditional \u201cgateway\u201d drugs. Consistent with our knowledge that the A\/A genotype results in reduced FAAH expression and activity in humans, subjects with the A\/A genotype were less likely to be THC dependent than subjects with either a C\/C or C\/A genotype (11% vs. 26%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). No association was observed between the A\/A genotype and risk for alcohol or tobacco regular use, or DSM IV dependence. Controlling for regular use of nicotine and sedatives, both identified as confounders, those with the A\/A genotype were at significantly reduced risk for being THC dependent (OR 0.25, 95% CI: 0.07\u20130.88) as compared with those with the C\/A or C\/C genotype, supporting a link between alterations in the endocannabinoid system and THC dependence. Unexpectedly, we found an increased risk for regular use of sedatives among the A\/A genotype group. The relationship between the FAAH A\/A genotype and risk for drug dependence in this study was drug class specific, suggesting it is not part of a more general drug abuse effect. These results, particularly the observation of altered risk for sedative drug use, should be investigated further in multiple ethnic populations. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.30491","type":"journal-article","created":{"date-parts":[[2007,2,9]],"date-time":"2007-02-09T00:42:55Z","timestamp":1170981775000},"page":"660-666","source":"Crossref","is-referenced-by-count":107,"title":["The fatty acid amide hydrolase C385A (P129T) missense variant in cannabis users: Studies of drug use and dependence in caucasians"],"prefix":"10.1002","volume":"144B","author":[{"given":"Rachel F.","family":"Tyndale","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer I.","family":"Payne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra 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