The examination of mechanisms by which genetic variability influences cannabis dependence and propensity to use marijuana is a high priority. However, there is a dearth of human studies on the identification of candidate phenotypes that serve as markers of cannabis dependence. The cannabinoid receptor type 1 (CB1), a G-coupled receptor encoded by the CNR1 gene, mediates the psychoactive effects and rewarding actions of marijuana (Ledent et al., 1999;Zhang et al., 2004). In addition, there is evidence that the fatty acid amidohydrolase (FAAH) gene may be an important candidate (Cravatt and Lichtman, 2003). Several polymorphisms in the CNR1 and one in the FAAH genes have been associated with cannabis dependence (Comings et al., 1997;Hopfer et al., 2006;Tyndale et al., 2007), cannabis-related intermediate phenotypes, including withdrawal and craving (Haughey et al, 2008), as well as positive subjective effects and physiological stimulation (Schacht et al., 2008). Despite previous suggestive findings, no studies have been conducted to date that test the association between CNR1 variability and key cannabis-related intermediate phenotypes related to sensitivity to the acute effects of cannabis, such as increased positive affect and reward sensitivity, decreased negative affect, and subjective stimulation and intoxication. Furthermore, it is largely unknown whether CNR1 or FAAH variation is associated with marijuana craving in non-abstinent users. The primary goal of this pilot research is to investigate variability in marijuana's acute and cue-elicited effects associated with empirically-chosen polymorphisms in the CNR1 and FAAH genes. In a 2 (genotype) X 2 (drug administration: marijuana with 2.8% delta-9-tetrahydrocannabinol (THC) vs. marijuana placebo;cue reactivity: neutral vs. marijuana cues) laboratory study, we will examine these effects in 80 Caucasian nontreatment- seeking heavy cannabis users. Genotyping of CNR1 and the FAAH genes will include empirically chosen candidate single nucleotide polymorphisms (SNPs) as well as tagSNPs. The long-term objective of this research is to identify genetic variation underlying individual differences in marijuana effects that may account for individual differences in susceptibility to marijuana dependence. Greater understanding of these mechanisms can inform genetically targeted pharmacotherapeutic approaches for treating cannabis dependence.
This research will help determine the reasons why some people who use marijuana may be at greater risk for abusing or becoming dependent on this drug. Examining individual differences in their genetic makeup will help uncover why some of these individuals may be more sensitive to marijuana's effects. This information could be of significant value to help identify people who would benefit from a particular treatment for marijuana.
| Aston, Elizabeth R; Farris, Samantha G; MacKillop, James et al. (2017) Latent factor structure of a behavioral economic marijuana demand curve. Psychopharmacology (Berl) 234:2421-2429 |
| Metrik, Jane; Farris, Samantha G; Aston, Elizabeth R et al. (2017) Development and initial validation of a marijuana cessation expectancies questionnaire. Drug Alcohol Depend 177:163-170 |
| Metrik, Jane; Aston, Elizabeth R; Kahler, Christopher W et al. (2016) Cue-elicited increases in incentive salience for marijuana: Craving, demand, and attentional bias. Drug Alcohol Depend 167:82-8 |
| Aston, Elizabeth R; Metrik, Jane; Amlung, Michael et al. (2016) Interrelationships between marijuana demand and discounting of delayed rewards: Convergence in behavioral economic methods. Drug Alcohol Depend 169:141-147 |
| Farris, Samantha G; Metrik, Jane (2016) Acute effects of cannabis on breath-holding duration. Exp Clin Psychopharmacol 24:305-12 |
| Farris, Samantha G; Metrik, Jane; Bonn-Miller, Marcel O et al. (2016) Anxiety Sensitivity and Distress Intolerance as Predictors of Cannabis Dependence Symptoms, Problems, and Craving: The Mediating Role of Coping Motives. J Stud Alcohol Drugs 77:889-897 |
| Aston, Elizabeth R; Metrik, Jane; MacKillop, James (2015) Further validation of a marijuana purchase task. Drug Alcohol Depend 152:32-8 |
| Metrik, Jane; Aston, Elizabeth R; Kahler, Christopher W et al. (2015) Marijuana's acute effects on cognitive bias for affective and marijuana cues. Exp Clin Psychopharmacol 23:339-50 |
| Day, Anne M; Metrik, Jane; Spillane, Nichea S et al. (2013) Working memory and impulsivity predict marijuana-related problems among frequent users. Drug Alcohol Depend 131:171-4 |
