title: Changes in cerebral CB1 receptor availability after acute and chronic alcohol abuse and monitored abstinence.
abstract: Involvement of the type 1 cannabinoid receptor (CB1R) in the effects of alcohol on the brain is supported by animal experiments, but how in vivo CB1R levels are altered in alcoholic patients is still unclear. To assess the short-time effects of a binge drinking episode on CB1R availability, 20 healthy social drinkers underwent [(18)F]MK-9470-positron emission tomography (PET) at baseline and after intravenous ethanol administration (ALC ACU). Moreover, 26 alcoholic patients underwent sequential CB1R 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 CB1R availability (+15.8%). In contrast, a global decreased CB1R 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 CB1R availability, especially in the cerebellum and parieto-occipital cortex. After abstinence, reduced CB1R 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 CB1R availability, chronic heavy drinking leads to reduced CB1R 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 CB1R 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.
authors.affiliation: Division of Nuclear Medicine, University Hospitals Leuven and Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium, MoSAIC, Molecular Small Animal Imaging Center, KU Leuven, 3000 Leuven, Belgium, Division of Psychiatry, University Hospital and KU Leuven, 3000 Leuven, Belgium, University Psychiatric Center, KU Leuven, 3070 Kortenberg, Belgium, Kliniek Broeders Alexianen, 3300 Tienen, Belgium, Laboratory for Radiopharmacy and Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium, and LIND, Leuven Institute for Neurobiology and Disease, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ceccarini
authors.forename: Titia
authors.initials: T
authors.lastname: Hompes
authors.forename: Anne
authors.initials: A
authors.lastname: Verhaeghen
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.forename: Hendrik
authors.initials: H
authors.lastname: Peuskens
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Stephan
authors.initials: S
authors.lastname: Claes
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
mesh_terms: D000208:Acute Disease; D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism / Q000523:psychology; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D063425:Binge Drinking / Q000000981:diagnostic imaging / Q000378:metabolism / Q000523:psychology; D001931:Brain Mapping; D002908:Chronic Disease; D015331:Cohort Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D013695:Temperance / Q000523:psychology*; D055815:Young Adult
chemical_list: C528731:MK-9470; D011725:Pyridines; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1
keywords: PET; abstinence; acute alcohol effect; alcoholism; cannabinoid CB1 receptor; chronic alcohol effect