MDMA Enhances Fear Extinction Learning: From Models to Mechanisms

Current research suggests that MDMA, or 3,4-methylenedioxymethamphetamine, may be particularly useful in the treatment of post-traumatic stress disorder (PTSD). Belonging to a class of substances known as entactogens, MDMA and its derivatives bear structural motifs common to both psychedelics and amphetamines, giving them a unique pharmacology with distinct subjective effects. As research continues to develop, MDMA has become regarded as a potential remedy for PTSD, with its first phase III clinical trial recently concluded. These results reaffirm that MDMA may indeed be effective when used as an adjunct to psychotherapy. This excitement begs the question: just how are MDMA’s positive effects mediated? What is the neurobiology underlying the positive outcomes observed? These aspects of MDMA-assisted therapy are poorly understood and warrant further investigation. Recent work offers important insights, with preclinical animal models exhibiting an enhanced resilience to experimentally learned fears upon MDMA administration, and with subsequent human trials reiterating this effect. Taken together, a biological explanation for MDMA’s ability to remedy PTSD may lie in its propensity to enhance fear extinction learning and memory reconsolidation.