Impact of Stress on the Endocannabinoid System: A [11C]-CURB Positron Emission Tomography Study in Early Psychosis

Background: Stress and traumatic experiences are well-established risk factors for psychiatric disorders. Stressful events can induce symptoms of anxiety and depression and may lead to overt psychosis, especially when there is an innate biological vulnerability. This study explores the role of the stress-regulating endocannabinoid system, specifically the activity of the enzyme fatty acid amid hydrolase (FAAH), a key regulatory enzyme for endocannabinoids, in association with stress by analysing data from healthy individuals and patients with psychosis. Methods: We performed a post-hoc exploratory analysis on 65 positron emission tomography scans using the selective FAAH radioligand [C-11]CURB, encompassing 30 patients with psychosis (6 female) and 35 healthy controls (19 female). The study aimed to examine the association between FAAH activity and stressful life events, assessed through the Recent Life Events, Survey of Life Experiences, and Hassles and Uplifts Scale. Results: There was a significant difference regarding the number of recent stressors with higher levels in patients compared to healthy subjects (Survey of Life Experiences: t = 4.88, p < 0.001, hassles: t = 3.14, p = 0.003), however there was no significant relationship of brain FAAH activity and stressful life events in any of the applied scales across groups (Recent Life Events: F-1,F-57 = 0.07, p = 0.80; Survey of Life Experiences: F-1,F-57= 1.75, p = 0.19; hassles: F-1,F-56 = 1.06, p = 0.31). Linear mixed models performed separately for each group revealed that there was a positive association between FAAH activity and Recent Life Events in patients with psychosis only (F-1,F-25 = 8.07, p = 0.009). Conclusions: Our data reveal a significant disparity in recent stressors between the two groups, and a correlation between brain FAAH activity and stressful life events in patients with psychosis only. This suggests a complex interplay between stress and the endocannabinoid system.