Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme. (23rd April 2019)

• Record Type: Journal Article
• Authors: Hindocha, Chandni; Freeman, Tom P.; Schafer, Grainne; Gardner, Chelsea; Bloomfield, Michael A.P.; Bramon, Elvira; Morgan, Celia J.A.; Curran, H. Valerie
• Is Part Of: Addiction biology. Volume 25:Number 3(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-04-23
• Subjects: addiction -- cannabis -- CBD -- craving -- endophenotype -- salience -- THC; Substance abuse -- Periodicals; Substance abuse -- Physiological aspects -- Periodicals; Substance-Related Disorders -- periodicals; 616.86
• DOI: 10.1111/adb.12762
• Languages: English
• ISSNs: 1355-6215

Abstract

Abstract: Understanding genetic factors that contribute to cannabis use disorder (CUD) is important, but to date, findings have been equivocal. Single‐nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 gene (CNR1; rs1049353 and rs806378) and fatty acid amide hydrolase (FAAH) gene (rs324420) have been implicated in CUD. Their relationship to addiction endophenotypes such as cannabis‐related state satiety, the salience of appetitive cues, and craving after acute cannabinoid administration has not been investigated. Forty‐eight cannabis users participated in a double‐blind, placebo‐controlled, four‐way crossover experiment where they were administered treatments in a randomized order via vaporization: placebo, Δ 9 ‐tetrahydrocannabinol (THC) (8 mg), THC + cannabidiol (THC + CBD) (8 + 16 mg), and CBD (16 mg). Cannabis‐related state satiety, appetitive cue salience (cannabis and food), and cannabis craving were assessed each day. Participants were genotyped for rs1049353, rs806378, and rs324420. Results indicated that CNR1 rs1049353 GG carriers showed increased state satiety after THC/THC + CBD administration in comparison with placebo and reduced the salience of appetitive cues after THC in comparison with CBD administration; A carriers did not vary on either of these measures indicative of a vulnerability to CUD. CNR1 rs806378 CC carriers showed greater salience to appetitive cues in comparison with T carriers, but there was no evidence for changes in state satiety. FAAH rs324420 A carriers showed greater bias to appetitive cues after THC, in comparison with CC carriers. FAAH CC carriers showed reduced bias after THC in comparison with CBD. No SNPs modulated craving. These findings identify candidate neurocognitive mechanisms through which endocannabinoid system genetics may influence vulnerability to CUD. Abstract : Our study identifies how variants in the endocannabinoid systems (eCBs) modulate the addiction‐related response to cannabis, after acute administration of cannabinoids via vaporization. Endophenotypes of addiction include appetitive cue salience (results pictured), state satiety, and craving. We found that variation in eCBs genetics predicted drug cue salience and feelings of cannabis‐induced satiety but not craving. As such, this study provides preliminary evidence of neurocognitive mechanisms through which eCBs genetics may influence vulnerability to cannabis use disorder.