A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy

Post-traumatic stress disorder (PTSD) affects millions worldwide, with 40–70% of patients experiencing refractory disease despite available treatments. MDMA, like classic psychedelics such as psilocybin, has been used to enhance psychotherapy since its discovery, but research into its mechanisms has been limited due to its Schedule 1 classification. The pro-social effects of MDMA are thought to improve therapeutic alliance and facilitate trauma processing, but this may not fully explain its efficacy. A more nuanced explanation combines MDMA's pro-social effects with molecular mechanisms, such as increased brain-derived neurotrophic factor (BDNF) availability in fear memory learning pathways, potentially accounting for its therapeutic actions in PTSD.

Study at a glance

Abstract

Post-traumatic stress disorder (PTSD) is a devastating psychiatric disorder afflicting millions of people around the world. Characterized by severe anxiety, intrusive thoughts, pervasive nightmares, an assortment of somatic symptoms, associations with severe long-term health problems, and an elevated risk of suicide, as much as 40–70% of patients suffer from refractory disease. 3,4-Methylenedioxy-methamphetamine (MDMA), like classic psychedelics such as psilocybin, have been used to enhance the efficacy of psychotherapy almost since their discovery, but due to their perceived potential for abuse and inclusion on USFDA (United States Food and Drug Administration) schedule 1, research into the mechanism by which they produce improvements in PTSD symptomology has been limited. Nevertheless, several compelling rationales have been explored, with the pro-social effects of MDMA thought to enhance therapeutic alliance and thus facilitate therapist-assisted trauma processing. This may be insufficient to fully explain the efficacy of MDMA in the treatment of psychiatric illness. Molecular mechanisms such as the MDMA mediated increase of brain-derived neurotrophic factor (BDNF) availability in the fear memory learning pathways combined with MDMA's pro-social effects may provide a more nuanced explanation for the therapeutic actions of MDMA.