Complex relationship between endocannabinoids, fatty acid amide hydrolase, and stress reactivity in human intrusive memories of analogue trauma

The endocannabinoid system has been shown to be involved in posttraumatic stress disorder-like behaviours in animal and human subjects. However, to date no studies have tested the relationship between blood markers of endocannabinoid signalling and intrusive memory development in humans. Across two studies, we tested the relationship between endocannabinoid genotypes, blood markers of endocannabinoids AEA and 2-AG, and intrusive memories of violent imagery and film clips. In study 1, we found a significant effect of rs324420 genotype on explicit memory recall, with A allele carriers (indicative of higher AEA) recalling fewer negative memories. Post-task AEA was negatively associated with explicit recall but not intrusive memories, though post-task AEA and 2-AG did interact with rs324420 to predict intrusive memory frequency. In study 2, stress induced changes in AEA but not 2-AG were negatively associated with intrusive memory frequency. In summary, we found evidence that AEA is involved in explicit and intrusive memories of negative stimuli. Evidence from both studies suggests that lower AEA is associated with higher explicit and intrusive memories. These findings support animal literature and have implications for targeted treatments for negative memory symptomology in posttraumatic stress disorder. • Endocannabinoids and FAAH C385A genotype show complex links with stress and memory. • C385A impaired explicit memory and interacted with AEA and 2-AG to predict intrusions. • Stress-induced AEA was associated with higher intrusive memories of trauma footage. • Higher cortisol stress responses were linked to fewer short-term intrusive memories. • Findings support endocannabinoid reactivity, not static levels, as key to memory outcomes.