Cover Image

Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamat...

Full description

Saved in:
Bibliographic Details
Main Authors: Kroll, Sara Liane (Author) , Hulka, Lea M. (Author) , Kexel, Ann-Kathrin (Author) , Vonmoos, Matthias (Author) , Preller, Katrin H. (Author) , Treyer, Valerie (Author) , Ametamey, Simon M. (Author) , Baumgartner, Markus R. (Author) , Boost, Carola (Author) , Pahlisch, Franziska (Author) , Rohleder, Cathrin (Author) , Leweke, F. Markus (Author) , Quednow, Boris B. (Author)
Format: Article (Journal)
Language:English
Published: 19 October 2023
In: Translational Psychiatry
Year: 2023, Volume: 13, Issue: 1, Pages: 1-10
ISSN:2158-3188
DOI:10.1038/s41398-023-02628-7
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41398-023-02628-7
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41398-023-02628-7
Get full text
Author Notes:Sara L. Kroll, Lea M. Hulka, Ann-Kathrin Kexel, Matthias Vonmoos, Katrin H. Preller, Valerie Treyer, Simon M. Ametamey, Markus R. Baumgartner, Carola Boost, Franziska Pahlisch, Cathrin Rohleder, F. Markus Leweke and Boris B. Quednow
Description
Summary:Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N = 103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N = 92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N = 33; controls: N = 43). In an additional analysis using 11C-ABP688 positron emission tomography (PET) in a male subsample (CU: N = 18; controls: N = 16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence.
Item Description:Gesehen am 18.09.2024
Physical Description:Online Resource
ISSN:2158-3188
DOI:10.1038/s41398-023-02628-7

Similar Items