681. ENDOCANNABINOIDS AND INTRUSIVE MEMORIES: EVIDENCE FOR A ROLE OF ANANDAMIDE FROM TWO EXPERIMENTAL HUMAN STUDIES

Abstract Background Preclinical evidence strongly suggests that the endocannabinoid system (particularly the ligands anandamide and 2-AG) is involved in trauma responses and negative emotional memories, which are relevant to posttraumatic stress disorder (PTSD). However, few experimental studies have tested the relationship between the core PTSD symptom – intrusive memories – and endocannabinoids. Aims & Objectives The aim of these studies was to test the relationship between human biomarkers of anandamide and 2-AG signaling and intrusive memories to experimental stimuli. We hypothesized that both lower resting and stress-induced anandamide and 2-AG levels would be associated with higher reports of intrusive memories of negative stimuli, and that genotypes associated with lower anandamide and cannabinoid receptor expression would similarly be associated with higher reports of intrusive memories. Method Two experimental studies were conducted. In study one, cannabinoid genotyping data (rs324420 and rs2180619) was collected from N=269 participants after watching a series of violent images and reporting 2-day explicit and intrusive memories. A subset of participants (n=67) also had arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG) plasma measurements taken, and some (n=52) had PTSD. In study two, N=58 participants completed stress induction, a trauma film experiment, and had plasma AEA and 2-AG measured. Results There was a significant effect of rs324420 genotype on explicit memory recall (p=.002), with A allele carriers (indicative of higher anandamide) recalling fewer negative memories. Participants with PTSD and the G rs2180619 allele reported more intrusive memories (p=.022) compared to controls and to AA homozygote PTSD participants. Post-task AEA was negatively associated with explicit recall (p=.025) but not intrusive memories (p=.821). In study two, stress induced changes in anandamide (p=.020) but not 2-AG (p=.649) were negatively associated with intrusive memory frequency. Discussion & Conclusions Across two studies, we found evidence that anandamide is involved in explicit and intrusive memories of negative stimuli. Evidence from both studies suggests that lower anandamide is associated with higher explicit and intrusive memories. These findings support animal literature and have implications for targeted treatments for negative memory symptomology in PTSD.