CNR1 and FAAH variation and affective states induced by marijuana smoking

ABSTRACT

Background: Polymorphisms in cannabinoid receptor type 1 (encoded by CNR1) and fatty acid amide hydrolase (encoded by FAAH) have been associated with cannabis dependence, but it remains unknown whether variation within these genes influences cannabis’ acute effects on affect.

Objective: Conduct a secondary data analysis study to determine whether previously observed acute effects of tetrahydrocannabinol (THC) on mood was dependent upon variation in CNR1 and FAAH.

Methods: A balanced placebo design was used crossing marijuana administration (i.e., 0% THC vs. 2.8% THC) with stimulus expectancy. Participants (N = 118; 64% male) provided DNA and completed the Profile of Mood States questionnaire prior to and after smoking. Haplotypes were constructed from genotyped single nucleotide polymorphisms for CNR1 (rs1049353 and rs806368) and FAAH (rs4141964, rs324420, and rs11576941); rs2023239 (CNR1) and rs6703669 (FAAH) were not part of a phased haplotype block. Analyses tested both main and interaction effects for genotype across CNR1 and FAAH, and drug, and expectancy effects.

Results: THC increased levels of POMS Tension-Anxiety and Confusion-Bewilderment over and above the effects of variation in CNR1 and FAAH. Significant drug X genotype/haplotype and expectancy X genotype/haplotype interaction effects were observed for some but not all mood states [e.g., ‘C’ allele carriers of rs2023239 who received THC had higher levels of Anger-Hostility (β= 0.29 (0.12), p= .02) compared to those who received placebo].

Conclusion: These preliminary findings suggest individual differences in mood states after using marijuana depend on genetic variation. Such information might be useful in understanding either motivation for use of marijuana and/or risk for associated behaviors.

KEYWORDS:

• Cannabis
• THC
• CNR1
• FAAH
• Affect
• Balanced Placebo Design
• marijuana
• tetrahydrocannabinol

Disclosures

The authors declare they have no conflicts of interest. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Additional information

Funding

This work was supported by research grants from the National Institute on Alcohol Abuse and Alcoholism (R01AA025593) and the National Institute on Drug Abuse (DP1DA042103, R03DA027484, and R01DA044131).