{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:53:21Z","timestamp":1788274401972,"version":"build-2803163510"},"reference-count":102,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The stress response is a well-defined physiological function activated frequently by life events. However, sometimes the stress response can be inappropriate, excessive, or prolonged; in which case, it can hinder rather than help in coping with the stressor, impair normal functioning, and increase the risk of somatic and mental health disorders. There is a need for a more effective and safe pharmacological treatment that can dampen maladaptive stress responses. The endocannabinoid system is one of the main regulators of the stress response. A basal endocannabinoid tone inhibits the stress response, modulation of this tone permits\/curtails an active stress response, and chronic deficiency in the endocannabinoid tone is associated with the pathological complications of chronic stress. Cannabidiol is a safe exogenous cannabinoid enhancer of the endocannabinoid system that could be a useful treatment for stress. There have been seven double-blind placebo controlled clinical trials of CBD for stress on a combined total of 232 participants and one partially controlled study on 120 participants. All showed that CBD was effective in significantly reducing the stress response and was non-inferior to pharmaceutical comparators, when included. The clinical trial results are supported by the established mechanisms of action of CBD (including increased N-arachidonylethanolamine levels) and extensive real-world and preclinical evidence of the effectiveness of CBD for treating stress.<\/jats:p>","DOI":"10.3390\/jcm10245852","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T01:20:41Z","timestamp":1639444841000},"page":"5852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Enhancing Endocannabinoid Control of Stress with Cannabidiol"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-9310","authenticated-orcid":false,"given":"Jeremy","family":"Henson","sequence":"first","affiliation":[{"name":"Prince of Wales Clinical School, University of NSW, Sydney, NSW 2052, Australia"},{"name":"Medlab Clinical Ltd., Sydney, NSW 2015, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7490-9298","authenticated-orcid":false,"given":"Luis","family":"Vitetta","sequence":"additional","affiliation":[{"name":"Prince of Wales Clinical School, University of NSW, Sydney, NSW 2052, Australia"},{"name":"Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Quezada","sequence":"additional","affiliation":[{"name":"Medlab Clinical Ltd., Sydney, NSW 2015, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Hall","sequence":"additional","affiliation":[{"name":"Medlab Clinical Ltd., Sydney, NSW 2015, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Andrews, J., and Pruessner, J.C. 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