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Lower brain fatty acid amide hydrolase in treatment-seeking patients with alcohol use disorder: a positron emission tomography study with [C-11]CURB
Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada.
Ctr Addict & Mental Hlth, Canada.
Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada; Univ Toronto, Canada; Univ Toronto, Canada.
Ctr Addict & Mental Hlth, Canada; Ctr Addict & Mental Hlth, Canada; Univ Toronto, Canada.
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2020 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 45, no 8, p. 1289-1296Article in journal (Refereed) Published
Abstract [en]

The endocannabinoid enzyme, fatty acid amide hydrolase (FAAH), has been proposed as a therapeutic target for alcohol use disorder (AUD) and co-morbid psychiatric illnesses. Investigating this target in the living human brain and its relationship to clinical outcome is a critical step of informed drug development. Our objective was to establish whether brain FAAH levels are low in individuals with AUD and related to drinking behavior. In this pilot study, treatment-seeking patients with AUD completed two PET scans with the FAAH radiotracer [C-11]CURB after 3-7 days (n = 14) and 2-4 weeks (n = 9) of monitored abstinence. Healthy controls (n = 25) completed one scan. FAAH genetic polymorphism (rs324420) and blood concentrations of anandamide and other N-acylethanolamines metabolized by FAAH were determined and AUD symptoms assessed. In AUD, brain FAAH levels were globally lower than controls during early abstinence (F(1,36) = 5.447; p = 0.025)) and FAAH substrates (anandamide, oleoylethanolamide, and N-docosahexaenoylethanolamide) were significantly elevated (30-67%). No significant differences in FAAH or FAAH substrates were noted after 2-4 weeks abstinence. FAAH levels negatively correlated with drinks per week (r = -0.57, p = 0.032) and plasma concentrations of the three FAAH substrates (r > 0.57; p < 0.04)). Our findings suggest that early abstinence from alcohol in AUD is associated with transiently low brain FAAH levels, which are inversely related to heavier alcohol use and elevated plasma levels of FAAH substrates. Whether low FAAH is an adaptive beneficial response to chronic alcohol is unknown. Therapeutic strategies focusing on FAAH inhibition should consider the possibility that low FAAH during early abstinence may be related to drinking.

Place, publisher, year, edition, pages
SPRINGERNATURE , 2020. Vol. 45, no 8, p. 1289-1296
National Category
Pharmacology and Toxicology Substance Abuse
Identifiers
URN: urn:nbn:se:liu:diva-203497DOI: 10.1038/s41386-020-0606-2ISI: 000508150700002PubMedID: 31910433OAI: oai:DiVA.org:liu-203497DiVA, id: diva2:1858051
Note

Funding Agencies|National Institute of Health [R21AA026680, 1R21DA04529, NIH/NIAAAR21 1R21AA022246-01A1]; National Institute of Drug Abuse [NIH/NIAAAR21 1R21AA022246-01A1]; Ontario Mental Health Foundation; Canadian Institutes of Health Research Project Grant [PG389342]; Canada Research Chairs program (Canada Research Chair in Pharmacogenomics); Canadian Institutes of Health Research [FDN-154294]; CIHR [TMH109787]; Canada Research Chair in Brain Lipid Metabolism; Canada Foundation for Innovation; Ontario Ministry of Research and Innovation; Canadian Institutes of Health Research Doctoral Award-S Frederick Banting and Charles Best Canada Graduate Scholarships (CGS-D); Centre for Addiction and Mental Health; CAMH Foundation; Canopy (CAMH); Canopy (University of Toronto); Aphria (CAMH); Bioprojet; ACS; Alkermes; CIHR; NIH; Natural Sciences and Engineering Research Council of Canada; Canadian government; Canada Research Chairs program; Global Research Awards for Nicotine Dependence (GRAND); Pfizer; US NIH [R21AA026680, R21DA040066]; Jazz Pharmaceuticals; National Institute of Drug Abuse (Ontario Mental Health Foundation); Caskey Francis Award; Canadian Institute for Military and Veterans Health Research; Aphria (University of Toronto)

Available from: 2024-05-15 Created: 2024-05-15 Last updated: 2024-05-15

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Heilig, Markus

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Faculty of Medicine and Health SciencesCenter for Social and Affective NeurosciencePsykiatriska kliniken i Linköping
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