The fatty acid amide hydrolase C385A (P129T) missense variant in cannabis users: studies of drug use and dependence in Caucasians.
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.
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Among subjects who tried cannabis, those carrying a genetic variation in FAAH (C385A) were significantly less likely to develop CUD.
“Among subjects who tried cannabis, those carrying a genetic variation in FAAH (C385A) were significantly less likely to develop CUD 79.”
From Psychosocial and pharmacological interventions for the treatment of cannabis use disorder (2018) · cites this paper as [79]
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- Authors
- Tyndale, R. F., Payne, J. I., Gerber, A. L., & Sipe, J. C.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Dalhousie University (CA)
- Scripps Research Institute (US)
- Corresponding author
- Tyndale, Rachel F.
- Venue
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2007-02-08
- Volume
- 144B
- Issue
- 5
- Pages
- 660-666
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2141724621
- Cited by
- 117
- References
- 35
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 11 · 2023: 8 · 2022: 10 · 2021: 3 · 2020: 5 · 2019: 11 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 8 · 2013: 7 · 2012: 4
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre for Addiction and Mental Health
- Canada Research Chairs
- National Institutes of Health (5r01da015749-03)
- Canadian Institutes of Health Research
- National Institute on Drug Abuse (DA015749)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- fatty acid amide hydrolase, cannabis use disorder, endocannabinoid system, anandamide, sedative use, alcohol consumption, nicotine use, gateway drugs, genetic risk, Caucasians
- MeSH terms
- Fatty Acid Amide Hydrolases, Adult, Alcohol Drinking, Amidohydrolases, Canada, Cannabinoids, Female, Genotype, Humans, Male, Marijuana Smoking, Smoking, Logistic Models, Substance-Related Disorders, Genetic Predisposition to Disease, Mutation, Missense
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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