Abstract
Fear and anxiety perform essential protective roles, yet when they become
dysregulated, they can trap trauma survivors in persistent hypervigilance and
distress. Post-traumatic stress disorder (PTSD) manifests as intrusive memories,
avoidance, and heightened arousal long after the precipitating event. Although
current pharmacotherapies – including selective serotonin reuptake inhibitors,
adrenergic blockers, benzodiazepines, and atypical antipsychotics – provide
relief for some, many patients contend with residual symptoms or intolerable
adverse effects. Recent discoveries position the endocannabinoid system as a
pivotal regulator of fear acquisition, consolidation, and extinction. Clinical
observations of altered anandamide levels and cannabinoid receptor CB₁
upregulation in individuals with severe PTSD underscore the therapeutic
potential of restoring endocannabinoid tone. Preclinical studies demonstrate
that direct CB₁ agonists, fatty acid amide hydrolase (FAAH) inhibitors, and
phytocannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD) can
facilitate extinction learning and attenuate anxiety-like behaviours.
Preliminary human trials report that nabilone alleviates trauma-related
nightmares and that acute cannabinoid administration modulates amygdala
reactivity to a threat. Yet optimal dosing strategies, sex-specific responses,
and ideal THC:CBD ratios remain to be defined. Self-medication with cannabis can
offer transient relief but carries a risk of cannabis use disorder and potential
worsening of PTSD symptoms. By elucidating molecular targets – including CB₁,
CB₂, FAAH, and monoacylglycerol lipase – this review outlines a strategic
framework for next-generation cannabinoid-based interventions. Harnessing the
endocannabinoid system promises to expand the therapeutic arsenal for PTSD,
offering hope for more effective and better-tolerated treatments.
Keywords
posttraumatic stress disorder (PTSD) - stress - anxiety disorders
