Modulation of the endocannabinoid system by sex hormones: Implications for posttraumatic stress disorder.

Highlights • PTSD involves dysregulated memory consolidation, extinction learning and negative feedback of the HPA axis. • As the endocannabinoid system underlies these processes, it is a promising target for PTSD treatment. • Marked sex and sex-hormone differences are apparent in PTSD, and these extend to the endocannabinoid system. • Hormonal mechanisms may drive the PTSD gender disparity through the endocannabinoid system. Abstract The endocannabinoid system is an increasingly recognised pharmacological target for treating stress and anxiety disorders, including post-traumatic stress disorder (PTSD). Recent preclinical developments have implicated the endocannabinoid system in stress responses, emotional memories and fear extinction, all critical to PTSD aetiology. However, preclinical research in endocannabinoid biology has neglected the influential role of sex hormone differences on PTSD symptomology, which is particularly important given that PTSD is twice as common in women as in men. In this review, we compile and consider the evidence that the endocannabinoid system is influenced by ovarian hormones, with application to stress disorders such as PTSD. It is clear that therapeutic modulation of the endocannabinoid system needs to be approached with awareness of ovarian hormonal influences, and knowledge of these influences may enhance treatment outcomes for female PTSD populations. [ABSTRACT FROM AUTHOR]