{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:14:31Z","timestamp":1787004871093,"version":"build-2736575974"},"reference-count":67,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fear and anxiety perform essential protective roles, yet when they become\n                    dysregulated, they can trap trauma survivors in persistent hypervigilance and\n                    distress. Post-traumatic stress disorder (PTSD) manifests as intrusive memories,\n                    avoidance, and heightened arousal long after the precipitating event. Although\n                    current pharmacotherapies \u2013 including selective serotonin reuptake inhibitors,\n                    adrenergic blockers, benzodiazepines, and atypical antipsychotics \u2013 provide\n                    relief for some, many patients contend with residual symptoms or intolerable\n                    adverse effects. Recent discoveries position the endocannabinoid system as a\n                    pivotal regulator of fear acquisition, consolidation, and extinction. Clinical\n                    observations of altered anandamide levels and cannabinoid receptor CB\u2081\n                    upregulation in individuals with severe PTSD underscore the therapeutic\n                    potential of restoring endocannabinoid tone. Preclinical studies demonstrate\n                    that direct CB\u2081 agonists, fatty acid amide hydrolase (FAAH) inhibitors, and\n                    phytocannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD) can\n                    facilitate extinction learning and attenuate anxiety-like behaviours.\n                    Preliminary human trials report that nabilone alleviates trauma-related\n                    nightmares and that acute cannabinoid administration modulates amygdala\n                    reactivity to a threat. Yet optimal dosing strategies, sex-specific responses,\n                    and ideal THC:CBD ratios remain to be defined. Self-medication with cannabis can\n                    offer transient relief but carries a risk of cannabis use disorder and potential\n                    worsening of PTSD symptoms. By elucidating molecular targets \u2013 including CB\u2081,\n                    CB\u2082, FAAH, and monoacylglycerol lipase \u2013 this review outlines a strategic\n                    framework for next-generation cannabinoid-based interventions. Harnessing the\n                    endocannabinoid system promises to expand the therapeutic arsenal for PTSD,\n                    offering hope for more effective and better-tolerated treatments.<\/jats:p>","DOI":"10.1055\/a-2647-8030","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T22:49:12Z","timestamp":1754952552000},"page":"57-65","source":"Crossref","is-referenced-by-count":1,"title":["The Endocannabinoid System in PTSD: Molecular Targets for Modulating\n                    Fear and Anxiety"],"prefix":"10.1055","volume":"59","author":[{"given":"Stanley","family":"Lyndon","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, United States"},{"name":"Division of Neuropsychiatry, Brigham and Women\u2019s Hospital, Boston MA,\n                    United States"},{"name":"Center for Brain\/Mind Medicine, Mass General Brigham, Boston, MA,\n                    United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2470547017713297","DOI":"10.1177\/2470547017713297","article-title":"Post-Traumatic Stress Disorder: The Relationship Between the Fear Response and\n                    Chronic Stress","volume":"1","author":"L Y Maeng","year":"2017","journal-title":"Chronic Stress (Thousand Oaks)"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrn3339","article-title":"Biological studies of post-traumatic stress disorder","volume":"13","author":"R K Pitman","year":"2012","journal-title":"Nat Rev Neurosci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nature00839","article-title":"The endogenous cannabinoid system controls extinction of aversive memories","volume":"418","author":"G 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