February 15, 2021

Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial

Elevated Anandamide, Enhanced Recall of Fear Extinction

Post-Traumatic Stress Disorder (PTSD) is characterized by intrusive memories of life-threatening events accompanied by severe anxiety and sleeplessness that often adversely affect quality of life. PTSD has been reported to have a life-time prevalence of 7-8%. With numerous individuals affected by PTSD, additional treatment options are warranted. In this double-blind, placebo-controlled study, the authors aim to examine the effects of elevated levels of anandamide through inhibition of Fatty Acid Amide Hydroxylase (FAAH) on fear extinction and affective stress response. Sixteen participants received 4mg of FAAH inhibitor and 29 participants received placebo daily for 10 days. Both groups underwent a battery of test to assess anandamide levels, response to stress, and fear extinction on days 9 and 10. There were no adverse events observed during the study period and participants who received the FAAH inhibitor had significantly higher levels of anandamide than those who received placebo. Interestingly, though FAAH inhibition had no effects on learning of conditioned fear, enhanced recall of fear extinction memory after 24 hours was observed in participants who received the inhibitor. However, this effect was not evident immediately within the learning session. Additionally, FAAH inhibition decreased stress-induced affective response without affecting baseline affect. Though the sample size is small, the results nevertheless provide evidence that increasing anandamide levels through FAAH inhibition is a plausible mechanism of action in the treatment of PTSD. Larger clinical trials are needed to further elucidate the role of anandamide in PTSD management.


View This Research