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Endocannabinergic modulation of central serotonergic activity in healthy human volunteers
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 activat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024405/ https://www.ncbi.nlm.nih.gov/pubmed/36932421 http://dx.doi.org/10.1186/s12991-023-00437-2 |
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author | Emons, Barbara Arning, Larissa Makulla, Vera-Estelle Suchy, Maria-Theresia Tsikas, Dimitrios Lücke, Thomas Epplen, Jörg T. Juckel, Georg Roser, Patrik |
author_facet | Emons, Barbara Arning, Larissa Makulla, Vera-Estelle Suchy, Maria-Theresia Tsikas, Dimitrios Lücke, Thomas Epplen, Jörg T. Juckel, Georg Roser, Patrik |
author_sort | Emons, Barbara |
collection | PubMed |
description | 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 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the FAAH gene on the serotonergic and endocannabinoid system in 59 healthy volunteers. 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 (rs1049353, rs344420) was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method. RESULTS: Genotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the CNR1-A-allele-carriers, a reduced AEA (A-allele-carrier M = 0.66, SD = 0.24; GG genotype M = 0.72, SD = 0.24) and 2AG (A-allele-carriers M = 0.70, SD = 0.33; GG genotype M = 1.03, SD = 0.83) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed. CONCLUSIONS: Our results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression. |
format | Online Article Text |
id | pubmed-10024405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100244052023-03-19 Endocannabinergic modulation of central serotonergic activity in healthy human volunteers Emons, Barbara Arning, Larissa Makulla, Vera-Estelle Suchy, Maria-Theresia Tsikas, Dimitrios Lücke, Thomas Epplen, Jörg T. Juckel, Georg Roser, Patrik Ann Gen Psychiatry Primary Research 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 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the FAAH gene on the serotonergic and endocannabinoid system in 59 healthy volunteers. 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 (rs1049353, rs344420) was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method. RESULTS: Genotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the CNR1-A-allele-carriers, a reduced AEA (A-allele-carrier M = 0.66, SD = 0.24; GG genotype M = 0.72, SD = 0.24) and 2AG (A-allele-carriers M = 0.70, SD = 0.33; GG genotype M = 1.03, SD = 0.83) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed. CONCLUSIONS: Our results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression. BioMed Central 2023-03-17 /pmc/articles/PMC10024405/ /pubmed/36932421 http://dx.doi.org/10.1186/s12991-023-00437-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Emons, Barbara Arning, Larissa Makulla, Vera-Estelle Suchy, Maria-Theresia Tsikas, Dimitrios Lücke, Thomas Epplen, Jörg T. Juckel, Georg Roser, Patrik Endocannabinergic modulation of central serotonergic activity in healthy human volunteers |
title | Endocannabinergic modulation of central serotonergic activity in healthy human volunteers |
title_full | Endocannabinergic modulation of central serotonergic activity in healthy human volunteers |
title_fullStr | Endocannabinergic modulation of central serotonergic activity in healthy human volunteers |
title_full_unstemmed | Endocannabinergic modulation of central serotonergic activity in healthy human volunteers |
title_short | Endocannabinergic modulation of central serotonergic activity in healthy human volunteers |
title_sort | endocannabinergic modulation of central serotonergic activity in healthy human volunteers |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024405/ https://www.ncbi.nlm.nih.gov/pubmed/36932421 http://dx.doi.org/10.1186/s12991-023-00437-2 |
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