The role of endocannabinoid function in posttraumatic stress disorder: Modulating the risk phenotype and rendering effects of trauma

Posttraumatic stress disorder (PTSD) is a debilitating consequence of trauma in military and civilian settings. Substantial evidence implicates endocannabinoid function in three dimensions associated with risk for the disorder and in the etiology of essential symptoms. Negative (fear-avoidance) and positive (approach-reward) systems, and a dispositional dimension of control, modulate risk for PTSD and rely heavily on endocannabinoid function. Moreover, animal models associate an exaggerated fear response, characteristic of PTSD, with compromised endocannabinoid signaling, while plasticity in the same system renders effects of trauma in early life, fundamentally altering the stress response. Further implicating the endocannabinoid system, PTSD often co-occurs with cannabis use. Cannabis appears to alleviate negative affect states and symptoms of PTSD, possibly by normalizing endocannabinoid function. While this diverse evidence recommends the endocannabinoid system as a therapeutic target, it also reveals complexities that complicate efforts to develop such therapies. Scientific analysis of endocannabinoid function in PTSD will facilitate these efforts, while also informing a developing discussion on medical and recreational use of marijuana.