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...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
19 October 2023
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| In: |
Translational Psychiatry
Year: 2023, Volume: 13, 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 
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| 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 |
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| 245 | 1 | 0 | |a Plasma endocannabinoids in cocaine dependence and their relation to cerebral metabotropic glutamate receptor 5 density |c 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 |
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| 520 | |a 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. | ||
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