Association between ABCB1 rs2235048 Polymorphism and THC Pharmacokinetics and Subjective Effects following Smoked Cannabis in Young Adults
Justin Matheson, Yollanda J. Zhang, Bruna Brands, Christine M. Wickens, Arun K. Tiwari, Clement C. Zai, James L. Kennedy, Bernard Le Foll
Brain Sciences September 3, 2022 DOI: 10.3390/brainsci12091189 via OpenAlex
Summary
A genetic variant of ABCB1, which encodes a protein that pumps substances out of cells, may influence how the body processes THC from smoked cannabis. In 48 young adults who used cannabis 1–4 days per week, those carrying a C allele at the rs2235048 polymorphism had higher blood levels of THC metabolites after smoking a single cannabis cigarette than those with the TT genotype. C-allele carriers also reported using cannabis more frequently each week and greater drug liking. No other subjective drug effects differed between groups. The findings are preliminary and suggest that ABCB1 could affect cannabis-related traits and risk for cannabis use disorder, but larger studies are needed.
Study at a glance
| Characteristics | Placebo-controlled human laboratory experiment Peer reviewed |
|---|---|
| Sample size | 48 |
| Population | Young adults aged 19–25 years reporting 1–4 days of cannabis use per week |
| Intervention | smoked cannabis |
| Topics | Cannabis |
| Keywords | Delta-9-tetrahydrocannabinol Pharmacokinetics Genotype Placebo |
| Citations | 5 |
| Key finding | C-allele carriers of the ABCB1 rs2235048 polymorphism had higher blood levels of THC metabolites and reported greater cannabis use frequency and drug liking after smoking cannabis compared to TT genotype carriers. |
Abstract
Genetic influences on acute responses to psychoactive drugs may contribute to individual variability in addiction risk. ABCB1 is a human gene that encodes P-glycoprotein, an ATP-dependent efflux pump that may influence the pharmacokinetics of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. Using data from 48 young adults (aged 19–25 years) reporting 1–4 days of cannabis use per week who completed a placebo-controlled human laboratory experiment, we tested the hypothesis that the rs2235048 polymorphism of ABCB1 would influence acute responses to smoked cannabis. C-allele carriers reported on average greater frequency of weekly cannabis use compared to the TT genotype carriers (TC/CC mean ± SEM = 2.74 ± 0.14, TT = 1.85 ± 0.24, p = 0.004). After smoking a single cannabis cigarette to their desired high, C-allele carriers had higher area-under-the-curve (AUC) of both THC metabolites (11-OH-THC TC/CC = 7.18 ± 9.64, TT = 3.28 ± 3.40, p = 0.05; THC-COOH TC/CC = 95.21 ± 116.12, TT = 45.92 ± 42.38, p = 0.043), and these results were impact by self-reported ethnicity. There were no significant differences in self-reported subjective drug effects except for a greater AUC of visual analogue scale rating of drug liking (TC/CC = 35,398.33 ± 37,233.72, TT = 15,895.56 ± 13,200.68, p = 0.017). Our preliminary findings suggest that further work in a larger sample should investigate whether human ABCB1 influences cannabis-related phenotypes and plays a role in the risk of developing a cannabis use disorder.