Nature medicine
June 1, 2021
Jennifer M Mitchell, Michael Bogenschutz, Alia Lilienstein et al.
965 citations
A phase 3 clinical trial tested MDMA-assisted therapy against placebo for severe PTSD. Participants received manualized therapy with either MDMA or placebo alongside preparatory and integrative sessions. At two months after the last session, the MDMA group showed a significantly greater reduction in PTSD symptoms (average 24.4-point drop on the CAPS-5 scale) compared to the placebo group (13.9-point drop), with a large effect size. Functional impairment also improved more with MDMA. No serious safety issues such as abuse potential, suicidality, or heart rhythm problems were observed. The findings suggest MDMA-assisted therapy is highly effective and safe for severe PTSD, including in people with common co-occurring conditions.
Focus (American Psychiatric Publishing)
July 1, 2023
Jennifer M Mitchell, Michael Bogenschutz, Alia Lilienstein et al.
97 citations
A phase 3 clinical trial tested MDMA-assisted therapy for severe PTSD. In 90 participants randomized to receive either MDMA or placebo alongside therapy, those receiving MDMA showed a significantly larger reduction in PTSD symptoms, with an average decrease of 24.4 points on the CAPS-5 scale compared to 13.9 points in the placebo group. Functional impairment also improved more with MDMA. No serious safety issues like abuse potential or suicidality were observed. The treatment was effective even for patients with common co-occurring conditions such as depression or substance use history. The authors conclude MDMA-assisted therapy is a safe and highly effective treatment for severe PTSD.
Journal of psychiatric research
May 1, 2022
Timothy D Brewerton, Julie B Wang, Adele Lafrance et al.
81 citations
Among 89 individuals with severe PTSD enrolled in a placebo-controlled trial of MDMA-assisted therapy, 15% had eating disorder symptoms in the clinical range and 31.5% in the high-risk range at baseline, despite no active purging or low weight. After treatment, participants who received MDMA-assisted therapy showed significantly greater reductions in eating disorder symptoms compared to those who received placebo, especially among women with elevated baseline scores. The findings suggest that eating disorder psychopathology is common in severe PTSD and that MDMA-assisted therapy may reduce these co-occurring symptoms.
JAMA network open
June 3, 2024
Amy L McGuire, I Glenn Cohen, Dominic Sisti et al.
41 citations
A consensus statement from a 2023 meeting of 27 experts identifies 20 points of consensus across five ethical issues for integrating psychedelic medicines into mainstream medical practice: reparations and reciprocity, equity, and respect; informed consent; professional boundaries and physical touch; personal experience; and gatekeeping. The meeting included clinicians, researchers, Indigenous groups, industry, philanthropy, veterans, retreat facilitators, training programs, and bioethicists. The statement focuses on government-approved medical use in the US and abroad, emphasizing that policymakers must address challenges ahead while acknowledging the hopeful moment.
Frontiers in psychiatry
January 1, 2022
S Parker Singleton, Julie B Wang, Michael Mithoefer et al.
36 citations
In nine veterans and first-responders with chronic PTSD, MDMA-assisted therapy (MDMA-AT) did not significantly increase amygdala-hippocampus resting-state functional connectivity as hypothesized, showing only a trend. After treatment, brain activation during trauma memory recall decreased in the cuneus. Recovery from PTSD correlated with changes in four functional connections during autobiographical memory recall: left amygdala with left and right posterior cingulate cortex and left insula, and left isthmus cingulate with left posterior hippocampus. These findings suggest that amygdala, hippocampus, and insula functional connectivity may be a target of MDMA-AT, highlighting regions involved in memory processes.
Journal of Humanistic Psychology
June 23, 2021
Julie B. Wang, Jessica Lin, Leah Bedrosian et al.
22 citations
MDMA-assisted therapy (MDMA-AT) can be scaled across multiple clinic sites while maintaining high treatment fidelity. In an open-label study across 14 North American sites, cotherapist dyads were trained in a manualized protocol and administered three experimental sessions to participants with severe PTSD. Adherence to the therapy protocol was high across both dyads and sites. PTSD symptom severity, measured by the CAPS-5, decreased substantially after three sessions at 18 weeks. MDMA was well tolerated. These results indicate that the benefits of MDMA-AT for PTSD can be achieved in a multi-site, real-world clinical setting.
medRxiv Preprint Server
May 25, 2022
S. Parker Singleton, Julie B. Wang, Michael Mithoefer et al.
9 citations
preprint
In nine veterans and first-responders with chronic PTSD, MDMA-assisted therapy did not significantly increase amygdala-hippocampus resting-state functional connectivity as hypothesized, only showing a trend. After treatment, activation in the cuneus decreased when recalling traumatic versus neutral memories. The amount of PTSD recovery correlated with changes in four functional connections during autobiographical memory recall: left amygdala with left and right posterior cingulate cortex and left insula, and left isthmus cingulate with left posterior hippocampus. These findings suggest that MDMA-AT may alter functional connectivity in brain regions involved in memory and fear processing, but more research is needed to determine if these effects are specific to MDMA-AT compared to other PTSD treatments.
medRxiv Preprint Server
January 3, 2023
Bessel A. van der Kolk, Julie B. Wang, Rachel Yehuda et al.
2 citations
preprint
A Phase 3 clinical trial tested MDMA-assisted therapy (MDMA-AT) against placebo with therapy for severe PTSD. 85% of participants reported early childhood trauma, linked to deficits in emotional coping. MDMA-AT significantly improved alexithymia, self-compassion, and altered self-capacities compared to therapy alone. These changes address transdiagnostic mental processes that often hinder treatment response.
Frontiers in psychology
January 1, 2024
Kelley C O'Donnell, Lauren Okano, Michael Alpert et al.
A conceptual framework for MDMA-Assisted Therapy for PTSD centers on the participant's inner healing intelligence as the primary agent of change, with the therapeutic relationship as the core facilitative condition. This inner-directed, holistic, self-directed, relational, and trauma-informed approach includes a non-pathologizing stance toward embodied experiences, such as intense emotional expression, multiplicity, suicidal ideation, and transpersonal experiences. Therapists bring psychodynamic, somatic, and transpersonal awareness, empathic attunement, relational skillfulness, and cultural humility. MDMA with this psychotherapy outperformed placebo with psychotherapy in Phase 2 and 3 trials, though significant symptom reduction also occurred in the placebo group, supporting the psychotherapy model itself.
Kelley O'Donnell, Michael Alpert, Lauren Okano et al.
preprint
MDMA-Assisted Therapy for PTSD uses a short-term, intensive psychotherapy model that includes three sessions facilitated by MDMA along with non-drug therapy sessions. The MDMA helps recall and process traumatic memories and enhances learning in social contexts, integrating top-down and bottom-up trauma care. This paper describes the psychotherapeutic concepts and theories behind this approach, centering on the participant's inner healing intelligence as the main agent of change, with the therapeutic relationship as a core facilitative condition. Phase 2 and 3 trials showed MDMA with therapy outperformed placebo with therapy in reducing PTSD symptoms, though significant symptom reduction also occurred in participants who received only therapy.