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The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD

BACKGROUND: Although current treatments for Post-Traumatic Stress Disorder (PTSD) in war veterans are effective, unfortunately 30–50% still do not benefit from these treatments. Trauma-focused therapies, eg exposure therapy, are primarily based on extinction processes in which the endocannabinoid sy...

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Autores principales: Leen, N.A., de Weijer, A.D., van Rooij, S.J.H., Kennis, M., Baas, J.M.P., Geuze, E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190205/
https://www.ncbi.nlm.nih.gov/pubmed/35707677
http://dx.doi.org/10.1177/24705470221107290
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author Leen, N.A.
de Weijer, A.D.
van Rooij, S.J.H.
Kennis, M.
Baas, J.M.P.
Geuze, E.
author_facet Leen, N.A.
de Weijer, A.D.
van Rooij, S.J.H.
Kennis, M.
Baas, J.M.P.
Geuze, E.
author_sort Leen, N.A.
collection PubMed
description BACKGROUND: Although current treatments for Post-Traumatic Stress Disorder (PTSD) in war veterans are effective, unfortunately 30–50% still do not benefit from these treatments. Trauma-focused therapies, eg exposure therapy, are primarily based on extinction processes in which the endocannabinoid system (ECS) plays a significant role. Therefore, it can be hypothesized that poor treatment response on trauma-focused therapy due to extinction deficits may be associated with a poorly functioning ECS. The present study examined whether the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) are associated with post-treatment symptom reduction. METHODS: Blood plasma levels of AEA and 2-AG were determined in war veterans with a PTSD diagnosis (n = 54) and combat controls (n = 26) before and after a 6–8 month interval. During this period veterans with PTSD received trauma-focused therapy (eg cognitive behavioral therapy with exposure or eye-movement desensitization and reprocessing). Clinical symptoms were assessed before and after therapy with the Clinician Administered PTSD Scale (CAPS), State-Trait Anxiety Inventory (STAI) and Mood and Anxiety Symptom Questionnaire (MASQ). RESULTS: Regression analysis demonstrated that pretreatment endocannabinoid levels were not predictive of PTSD symptom reduction. Additionally, baseline endocannabinoid levels did not differ between either PTSD and combat controls or between combat controls, treatment responders, and non-responders. Only cortisol levels significantly decreased over time from pre- to posttreatment (p = .041). Endocannabinoid levels were significantly lower in individuals who reported cannabis use during their lifetime, independent of PTSD diagnosis. Furthermore, correlation analysis revealed that pretreatment 2-AG levels in PTSD were positively correlated with anxious arousal (r = .354, p = .015) and negatively with avoidance symptoms (r = -.271, p = .048). Both posttreatment AEA and 2-AG were positively correlated with trait anxiety (AEA r = .459, p = .003; 2-AG r = .423, p = .006), anxious arousal (AEA r = .351, p = .024; 2-AG r = .311, p = .048) and general distress depression symptoms (AEA r = .414, p = .007; 2-AG r = .374, p = .016). CONCLUSION: Since endocannabinoids are mainly generated ‘on demand’, future work could benefit by investigating endocannabinoid circulation under both baseline and stressful conditions. In line with previous research cannabis use was associated with lower endocannabinoid levels. The correlation analysis between pre- and posttreatment endocannabinoid levels and pre- and posttreatment clinical symptomatology were exploratory analysis and should be replicated in future research.
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spelling pubmed-91902052022-06-14 The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD Leen, N.A. de Weijer, A.D. van Rooij, S.J.H. Kennis, M. Baas, J.M.P. Geuze, E. Chronic Stress (Thousand Oaks) Original Article BACKGROUND: Although current treatments for Post-Traumatic Stress Disorder (PTSD) in war veterans are effective, unfortunately 30–50% still do not benefit from these treatments. Trauma-focused therapies, eg exposure therapy, are primarily based on extinction processes in which the endocannabinoid system (ECS) plays a significant role. Therefore, it can be hypothesized that poor treatment response on trauma-focused therapy due to extinction deficits may be associated with a poorly functioning ECS. The present study examined whether the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) are associated with post-treatment symptom reduction. METHODS: Blood plasma levels of AEA and 2-AG were determined in war veterans with a PTSD diagnosis (n = 54) and combat controls (n = 26) before and after a 6–8 month interval. During this period veterans with PTSD received trauma-focused therapy (eg cognitive behavioral therapy with exposure or eye-movement desensitization and reprocessing). Clinical symptoms were assessed before and after therapy with the Clinician Administered PTSD Scale (CAPS), State-Trait Anxiety Inventory (STAI) and Mood and Anxiety Symptom Questionnaire (MASQ). RESULTS: Regression analysis demonstrated that pretreatment endocannabinoid levels were not predictive of PTSD symptom reduction. Additionally, baseline endocannabinoid levels did not differ between either PTSD and combat controls or between combat controls, treatment responders, and non-responders. Only cortisol levels significantly decreased over time from pre- to posttreatment (p = .041). Endocannabinoid levels were significantly lower in individuals who reported cannabis use during their lifetime, independent of PTSD diagnosis. Furthermore, correlation analysis revealed that pretreatment 2-AG levels in PTSD were positively correlated with anxious arousal (r = .354, p = .015) and negatively with avoidance symptoms (r = -.271, p = .048). Both posttreatment AEA and 2-AG were positively correlated with trait anxiety (AEA r = .459, p = .003; 2-AG r = .423, p = .006), anxious arousal (AEA r = .351, p = .024; 2-AG r = .311, p = .048) and general distress depression symptoms (AEA r = .414, p = .007; 2-AG r = .374, p = .016). CONCLUSION: Since endocannabinoids are mainly generated ‘on demand’, future work could benefit by investigating endocannabinoid circulation under both baseline and stressful conditions. In line with previous research cannabis use was associated with lower endocannabinoid levels. The correlation analysis between pre- and posttreatment endocannabinoid levels and pre- and posttreatment clinical symptomatology were exploratory analysis and should be replicated in future research. SAGE Publications 2022-06-09 /pmc/articles/PMC9190205/ /pubmed/35707677 http://dx.doi.org/10.1177/24705470221107290 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Leen, N.A.
de Weijer, A.D.
van Rooij, S.J.H.
Kennis, M.
Baas, J.M.P.
Geuze, E.
The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD
title The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD
title_full The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD
title_fullStr The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD
title_full_unstemmed The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD
title_short The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD
title_sort role of the endocannabinoids 2-ag and anandamide in clinical symptoms and treatment outcome in veterans with ptsd
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190205/
https://www.ncbi.nlm.nih.gov/pubmed/35707677
http://dx.doi.org/10.1177/24705470221107290
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