Changes in cerebral type 1 cannabinoid receptor (CB1R) availability in ethanol-dependent patients after binge drinking and abstinence

Objectives The cerebral type 1 cannabinoid receptor (CB1R) plays an important role in human addiction. This study investigates the in vivo CB1R availability in alcoholic patients after an acute binge drinking episode and monitored abstinence, using PET and [¹⁸F]MK-9470.

Methods We investigated 16 male alcoholic patients (age: 34-61y). [¹⁸F]MK-9470 PET were performed after an acute binge drinking episode and after an ethanol abstinence period of 4 weeks. The control group consisted of 15 male healthy volunteers (age: 21-49y). Parametric modified standardized uptake value (mSUV) images, reflecting CB1R availability, were calculated. A predefined volume-of-interest (VOI; unpaired t-tests) statistical analysis was performed.

Results Global CB1R availability was decreased in grey matter regions (average: -8.7±2.2%) after binge drinking. Regional analysis in the reward circuit showed that relative CB1R availability was higher in insula (+2.4%; p=0.02) and nucleus accumbens (+4.5%; p=0.01). Abstinence conditions showed a further decrease of global CB1R availability (average: -14.8±1.6%). Regionally, relative significant increases in the nucleus accumbens (+5.4%; p=0.008) were observed.

Conclusions In ethanol-dependent patients, a globally decreased CB1R availability is observed in comparison to healthy volunteers, which is more pronounced after a period of abstinence. However, relative increased uptake in the insula and nucleus accumbens was found. These results indicate that central CB1R are altered in ethanol abuse giving a potential rationale for pharmacotherapy.

Research Support Merck & Co, Inc. is acknowledged for providing of the [¹⁸F]MK-9470 precursor. KVL and SC are Senior Clinical Investigator of the Flemish Fund of Scientific Research.