{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:08:49Z","timestamp":1791288529255,"version":"4.3.0"},"reference-count":227,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"NIDA","doi-asserted-by":"publisher","award":["DA042178"],"award-info":[{"award-number":["DA042178"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"NIDA","doi-asserted-by":"publisher","award":["PJT-148633"],"award-info":[{"award-number":["PJT-148633"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"publisher","award":["DA042178"],"award-info":[{"award-number":["DA042178"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"publisher","award":["PJT-148633"],"award-info":[{"award-number":["PJT-148633"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: There is a growing liberalization of cannabis-based preparations for medical and recreational use. In multiple instances, anxiety and depression are cited as either a primary or a secondary reason for the use of cannabinoids. Aim: The purpose of this review is to explore the association between depression or anxiety and the dysregulation of the endogenous endocannabinoid system (ECS), as well as the use of phytocannabinoids and synthetic cannabinoids in the remediation of depression\/anxiety symptoms. After a brief description of the constituents of cannabis, cannabinoid receptors and the endocannabinoid system, the most important evidence is presented for the involvement of cannabinoids in depression and anxiety both in human and from animal models of depression and anxiety. Finally, evidence is presented for the clinical use of cannabinoids to treat depression and anxiety. Conclusions: Although the common belief that cannabinoids, including cannabis, its main studied components\u2014tetrahydrocannabinol (THC) and cannabidiol (CBD)\u2014or other synthetic derivatives have been suggested to have a therapeutic role for certain mental health conditions, all recent systematic reviews that we report have concluded that the evidence that cannabinoids improve depressive and anxiety disorders is weak, of very-low-quality, and offers no guidance on the use of cannabinoids for mental health conditions within a regulatory framework. There is an urgent need for high-quality studies examining the effects of cannabinoids on mental disorders in general and depression\/anxiety in particular, as well as the consequences of long-term use of these preparations due to possible risks such as addiction and even reversal of improvement.<\/jats:p>","DOI":"10.3390\/brainsci13020325","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T02:01:10Z","timestamp":1676426470000},"page":"325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Endocannabinoid System and Exogenous Cannabinoids in Depression and Anxiety: A Review"],"prefix":"10.3390","volume":"13","author":[{"given":"Ahmed","family":"Hasbi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertha K.","family":"Madras","sequence":"additional","affiliation":[{"name":"McLean Hospital, Belmont, MA 02478, USA"},{"name":"Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.lfs.2005.09.011","article-title":"Chemical constituents of marijuana: The complex mixture of natural cannabinoids","volume":"78","author":"ElSohly","year":"2005","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1021\/ja01062a046","article-title":"Isolation, structure and partialsynthesis of anactive constituent of hashish","volume":"86","author":"Gaoni","year":"1964","journal-title":"J. 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