Endocannabinergic modulation of central serotonergic activity in healthy human volunteers

  • \(\bf Background\) The serotonergic and the endocannabinoid system are involved in the etiology of depression. Depressive patients exhibit low serotonergic activity and decreased level of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2AG). Since the cannabinoid (CB) 1 receptor is activated by endogenous ligands such as AEA and 2AG, whose concentration are controlled by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively, we investigated the effects on serotonergic utilization. In this study, we investigated the impact of the rs1049353 single-nucleotide polymorphism (SNP) of the cannabinoid receptor 1 \(\it (CNR1)\) gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the \(\it FAAH\) gene on the serotonergic and endocannabinoid system in 59 healthy volunteers. \(\bf Methods\) Serotonergic activity was measured by loudness dependence of auditory-evoked potentials (LDAEP). Plasma concentrations of AEA, 2AG and its inactive isomer 1AG were determined by mass spectrometry. Genotyping of two SNPs \(\textit {(rs1049353, rs344420)}\) was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method. \(\bf Results\) Genotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the \(\it CNR1\)-A-allele-carriers, a reduced AEA (A-allele-carrier \(\textit {M = 0.66}\), SD = \(\it 0.24\); GG genotype \(\textit {M = 0.72}\), SD = \(\it 0.24\)) and 2AG (A-allele-carriers \(\textit {M = 0.70}\), SD = \(\it 0.33\); GG genotype M = 1.03, SD = \(\it 0.83\)) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed. \(\bf Conclusions\) Our results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression.

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Author:Barbara EmonsORCiDGND, Larissa ArningORCiDGND, Vera-Estelle MakullaGND, Maria-Theresia SuchyGND, Dimitrios TsikasORCiDGND, Thomas LückeGND, Jörg T. EpplenORCiDGND, Georg JuckelORCiDGND, Patrik RoserGND
Parent Title (English):Annals of general psychiatry
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Date of Publication (online):2024/01/09
Date of first Publication:2023/03/17
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
CNR1 gene; Depression; Endocannabinoids (2AG, AEA); FAAH gene; LDAEP; Serotonergic system
Issue:Article 11
First Page:11-1
Last Page:11-9
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:LWL-Universitätsklinikum Bochum, Klinik für Psychiatrie, Psychotherapie und Präventivmedizin
Dewey Decimal Classification:Philosophie und Psychologie / Psychologie
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International