Marijuana withdrawal and craving: influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes.

AIM

To examine whether withdrawal after abstinence and cue-elicited craving were associated with polymorphisms within two genes involved in regulating the endocannabinoid system, cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH). Two single nucleotide polymorphisms (SNPs) in the CNR1 (rs2023239) and FAAH (rs324420) genes, associated previously with substance abuse and functional changes in cannabinoid regulation, were examined in a sample of daily marijuana smokers.

PARTICIPANTS

Participants were 105 students at the University of Colorado, Boulder between the ages of 18 and 25 years who reported smoking marijuana daily.

MEASUREMENTS

Participants were assessed once at baseline and again after 5 days of abstinence, during which they were exposed to a cue-elicited craving paradigm. Outcome measures were withdrawal and craving collected using self-reported questionnaires. In addition, urine samples were collected at baseline and on day 5 for the purposes of 11-nor-9-carboxy-Delta9-tetrahydrocannabinol (THC-COOH) metabolite analysis.

FINDINGS

Between the two sessions, THC-COOH metabolite levels decreased significantly, while measures of withdrawal and craving increased significantly. The CNR1 SNP displayed a significant abstinence x genotype interaction on withdrawal, as well as a main effect on overall levels of craving, while the FAAH SNP displayed a significant abstinence x genotype interaction on craving.

CONCLUSIONS

These genetic findings may have both etiological and treatment implications. However, longitudinal studies will be needed to clarify whether these genetic variations influence the trajectory of marijuana use/dependence. The identification of underlying genetic differences in phenotypes such as craving and withdrawal may aid genetically targeted approaches to the treatment of cannabis dependence.