AIMS: To describe differences in the expression of genes encoding cannabinoid receptors (CNR1, CNR2), the associated receptor GRP55 and the enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGLL) between individuals with alcohol use disorder (AUD) and controls in key mesocorticolimbic brain regions.

DESIGN: Case-control, observational postmortem study comparing gene expression in brain tissue from individuals diagnosed with AUD and matched controls. The study was not pre-registered and should therefore be considered exploratory. The setting was the Brain collection from the New South Wales Tissue Resource Centre (NSWTRC) at the University of Sydney, Australia.

PARTICIPANTS/CASES: Brain samples were obtained from 18 patients with AUD (mean alcohol use = 35.5 ± 8.7 drinking years) and 18 controls (C). Groups were matched for age (AUD: 55.8 ± 9; C: 56.3 ± 9.4) and postmortem interval (AUD: 39.7 ± 16.9 h; C: 31.8 ± 13.2 h).

MEASUREMENTS: Relative gene expression of CNR1, CNR2, GPR55, FAAH and MGLL was quantified using real-time polymerase chain reaction (qPCR) in the prefrontal cortex (PFC) and nucleus accumbens (NAc).

FINDINGS: Compared with controls, individuals with AUD showed higher CNR1 in the PFC (+125%) and NAc (+78%) and lower CNR2 expression in both regions (PFC: -50%; NAc: -49%). GPR55 was higher in the PFC (+19%) and lower in the NAc (-51%). FAAH expression was lower in the PFC (-15%) and higher in the NAc (+24%), whereas MGLL expression did not differ in the PFC and was lower in the NAc (-15%).

CONCLUSIONS: This descriptive postmortem study identifying region-specific differences in endocannabinoid system gene expression between individuals with alcohol use disorder (AUD) and controls supports an involvement of the endocannabinoid system in the neuropathological features associated with AUD, although causal relationships cannot be inferred.