Changes in Cerebral CB sub(1) Receptor Availability after Acute and Chronic Alcohol Abuse and Monitored Abstinence

Involvement of the type 1 cannabinoid receptor (CB sub(1) R) in the effects of alcohol on the brain is supported by animal experiments, but how in vivo CB sub(1) R levels are altered in alcoholic patients is still unclear. To assess the short-time effects of a binge drinking episode on CB sub(1) R availability, 20 healthy social drinkers underwent [ super(18) F]MK-9470-positron emission tomography (PET) at baseline and after intravenous ethanol administration (ALC ACU). Moreover, 26 alcoholic patients underwent sequential CB sub(1) R PET after chronic heavy drinking (ALC CHR) and after 1 month of abstinence (ALC ABST). Seventeen healthy subjects served as controls. Compared with baseline, ALC ACU resulted in a global increase of CB sub(1) R availability (+15.8%). In contrast, a global decreased CB sub(1) R availability was found in ALC CHR patients (-16.1%) compared with controls, which remained unaltered after abstinence (-17.0%). Voxel-based analysis showed that ALC CHR patients had reduced CB sub(1) R availability, especially in the cerebellum and parieto-occipital cortex. After abstinence, reduced CB sub(1) R availability extended also to other areas such as the ventral striatum and mesotemporal lobe. In conclusion, whereas the acute alcohol effect is an increase in CB sub(1) R availability, chronic heavy drinking leads to reduced CB sub(1) R availability that is not reversible after 1 month of abstinence. Longer follow-up is required to differentiate whether this is a compensatory effect of repeated endocannabinoid overstimulation or an enduring trait-like feature. An enhanced CB sub(1) R signaling may offer a new therapeutic direction for treatment of the negative affective state produced by alcohol withdrawal and abstinence, which is critical for the maintenance of alcohol addiction.