MDMA enhances the extinction of fear memories in a translational behavioral model, an effect that depends on the serotonin transporter (5-HTT) and the 5-HT2A receptor. These findings support the potential use of MDMA as an adjunct to exposure therapy for fear-related disorders and highlight important pharmacological considerations for patients who are often treated with serotonin reuptake inhibitors.
A randomized placebo-controlled trial tested whether MDMA enhances fear extinction retention in healthy adults. Participants underwent fear conditioning, then received 100 mg MDMA or placebo before extinction training. Fear retention was tested 48 hours later. MDMA was well-tolerated with no serious adverse events. While the overall analysis showed no significant group difference in extinction retention between training and test sessions, a significantly larger proportion of the MDMA group retained extinction learning compared to the placebo group. The results provide a rationale for further research into MDMA's potential effects on fear extinction.