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

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.

Consciousness-Pathology Relationship: Formation of Health and Disease via Psychological Suggestion

“…A study examining the effects of stress and positive emotions on vaccine response revealed that individuals with a positive emotional style had significantly higher levels of antibodies post-vaccination, with a p-value of 0.02 and an effect size of 0.47. This finding suggests that psychological factors can modulate the immune system's response to vaccines [16][17] .This laboratory-based evidence underscores the impactful role of psychological suggestion in modulating the immune system's response to vaccines. The observed correlation between positive emotional states and enhanced antibody production provides a tangible link between psychological factors and physiological outcomes.…”

Structural Neuroimaging of Hippocampus and Amygdala Subregions in Posttraumatic Stress Disorder: A Scoping Review

“…This review suggests conceptual and methodological ways in which future studies can overcome current barriers and shed light on the specific roles of these limbic subregions in posttraumatic psychopathology. Consequently, these efforts may pave the way for novel therapeutic strategies for PTSD prevention and treatment ( 132 , 133 , 134 ).…”

Psychedelic Therapy: A Primer for Primary Care Clinicians—3,4-Methylenedioxy-methamphetamine (MDMA)

“…By upregulating BDNF, MDMA may stimulate neuroplasticity and restore impaired synaptic connections within the amygdala, and enhanced connectivity with the hippocampus may then "unlock" the memory of the trauma. 38 Furthermore, reduced blood flow in the amygdala may correspond to a decrease in anxiety, 35,39 enabling recipients of MDMA-assisted therapy to face the traumatic memory with less fear.…”