The fatty acid amide hydrolase C385A (P129T) missense variant in cannabis users: studies of drug use and dependence in Caucasians.
Rachel F. Tyndale, Jennifer I Payne, Alexandra L Gerber, Jack C Sipe
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics July 5, 2007 DOI: 10.1002/ajmg.b.30491 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 749 |
| Population | Adult Caucasians |
| Measures | DSM IV dependence |
| Topics | Addiction Cannabis |
| Key findings | The FAAH A/A genotype was associated with lower likelihood of THC dependence (11% vs. 26%) and reduced odds of THC dependence after adjustment (OR 0.25), but not with alcohol or tobacco regular use or dependence. The authors also report an unexpected increased risk for regular sedative use among A/A carriers and suggest the effect is drug-class specific. |
Abstract
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-signaling lipids including the endogenous cannabinoid 1 receptor agonist anandamide. We investigated in adult Caucasians (N = 749) whether this FAAH variant altered the risk for trying, regular use of or dependence on cannabis, alcohol or nicotine, traditional "gateway" 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%, P < 0.05). 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: 0.07-0.88) 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.
Comparable studies
Other observational and cohort studies on cannabis for addiction, most cited first.
Citations in the library
Cited by 3
- Challenges and considerations for treating PTSD with medicinal cannabis: the Australian clinician's perspective. Expert Review of Clinical Pharmacology 2023
- PET imaging of FAAH in chronic Cannabis users: longitudinal assessment during short-term abstinence. Neuropsychopharmacology May 9, 2026
- The endocannabinoid system as a target for the treatment of cannabis dependence Neuropharmacology July 19, 2008
Cites 2
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