Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme

Journal article


Hindocha, Chandni, Freeman, Tom P., Schafer, Grainne, Gardner, Chelsea, Bloomfield, Michael A. P., Bramon, Elvira, Morgan, Celia J.A. and Curran, Helen Valerie. (2020) Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the CB1 receptor and FAAH enzyme. Addiction Biology. 25(3), pp. 1 - 11. https://doi.org/10.1111/adb.12762
AuthorsHindocha, Chandni, Freeman, Tom P., Schafer, Grainne, Gardner, Chelsea, Bloomfield, Michael A. P., Bramon, Elvira, Morgan, Celia J.A. and Curran, Helen Valerie
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, Δ9‐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.

Keywordsaddiction; cannabis; CBD; craving; endophenotype; salience; THC
Year2020
JournalAddiction Biology
Journal citation25 (3), pp. 1 - 11
PublisherBlackwell Publishing Ltd
ISSN1355-6215
Digital Object Identifier (DOI)https://doi.org/10.1111/adb.12762
Scopus EID2-s2.0-85064645400
Page range1 - 11
Research GroupSchool of Philosophy
Place of publicationUnited Kingdom
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