Influence of Cannabinoid Receptor 1 Genetic Variants on the Subjective Effects of Smoked Cannabis

• Main Authors: Thomas Murphy, Justin Matheson, Robert E. Mann, Bruna Brands, Christine M. Wickens, Arun K. Tiwari, Clement C. Zai, James Kennedy, Bernard Le Foll
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: International Journal of Molecular Sciences
• Subjects: cannabis; Δ⁹-tetrahydrocannabinol; subjective effects; <i>CNR1</i> gene
• Online Access: https://www.mdpi.com/1422-0067/22/14/7388

As many jurisdictions consider relaxing cannabis legislation and usage is increasing in North America and other parts of the world, there is a need to explore the possible genetic differences underlying the subjective effects of cannabis. This pilot study investigated specific genetic variations within the cannabinoid receptor 1 (<i>CNR1</i>) gene for association with the subjective effects of smoked cannabis. Data were obtained from a double-blinded, placebo-controlled clinical trial studying the impact of cannabis intoxication on driving performance. Participants randomized to the active cannabis group who consented to secondary genetic analysis (<i>n</i> = 52) were genotyped at the <i>CNR1</i> rs1049353 and rs2023239 polymorphic areas. Maximum value and area under the curve (AUC) analyses were performed on subjective measures data. Analysis of subjective effects by genotype uncovered a global trend towards greater subjective effects for rs1049353 T-allele- and rs2023239 C-allele-carrying subjects. However, significant differences attributed to allelic identity were only documented for a subset of subjective effects. Our findings suggest that rs1049353 and rs2023239 minor allele carriers experience augmented subjective effects during acute cannabis intoxication.