Endocannabinoid system reactivity during stress processing in healthy humans

Stress underlies the development of various psychiatric disorders. Rodent studies suggest an involvement of the endocannabinoid system in the modulation of the stress response, which needs to be translated to humans. In this study, 22 healthy males (mean age: M = 22.7 years) were exposed to a thermal heat stressor in a fear conditioning paradigm and blood samples of the circulating endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were assessed. Additionally, electrodermal activity (EDA), task-related anxiety ratings and data on critical life experiences (CLE) were recorded. Interestingly, increases in 2-AG from pre-to-post stress correlated with: smaller stress responses (EDA), by trend more CLE, and greater conditioned anxiety. Smaller stress responses correlated with more CLE. We demonstrate a relation between endocannabinoid level changes from pre-to-post acute stress and the stress response. Our results suggest that investigating the role of 2-AG in the response to stress could be promising in finding treatments in the immediate aftermath of traumatic events.