Nature Medicine
June 1, 2021
Jennifer Mitchell, Michael P. 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 Mitchell, Michael P. 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.
PLoS One
January 10, 2024
Rachel Yehuda, Leah Bedrosian, Charlotte Harrison et al.
52 citations
In a randomized, double-blind, placebo-controlled Phase 3 trial of 90 participants with severe PTSD, MDMA-assisted therapy produced significantly greater improvements than therapy with placebo on measures of emotional coping and self-experience. Participants receiving MDMA showed larger gains on the Toronto Alexithymia Scale, the Self-Compassion Scale, and most factors of the Inventory of Altered Self-Capacities, including affect regulation and interpersonal functioning, with identity diffusion being the only exception. Most participants had histories of developmental trauma and multiple traumas. These findings suggest that MDMA-assisted therapy enhances psychological capacities that are often linked to poor treatment outcomes, offering insight into how psychedelic agents may reduce PTSD symptoms.
Frontiers in Psychiatry
January 1, 2022
S Parker Singleton, Julie B. Wang, Michael C 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.
Neuropharmacology
August 17, 2022
Jack E Henningfield, Marion A Coe, Roland R. Griffiths et al.
34 citations
New medicines containing classic hallucinogenic and entactogenic psychedelics like psilocybin, LSD, and MDMA are being developed for psychiatric and neurological disorders. These substances are currently Schedule I under the US Controlled Substances Act (CSA) and similarly controlled globally. The CSA framework governs research, drug approval, and rescheduling; upon FDA approval, a drug containing a Schedule I substance must be rescheduled. Abuse potential research informs the eight CSA factors used for rescheduling, as well as product labeling and required risk evaluation and mitigation strategies (REMS). Standard human abuse potential studies are problematic for strong hallucinogens like psilocybin, so alternative strategies are discussed. Abuse-related research may also illuminate mechanisms of action, therapeutic effects, and effects on brain, behavior, mood, spirituality, and consciousness.
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 C 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.
Journal of the American College of Emergency Physicians Open
August 30, 2025
Juan Carlos C. Montoy, Ralph C. Wang, Allison R. Coker et al.
3 citations
Between 2013 and 2022, calls to poison control centers involving psilocybin tripled, with nearly all of the increase occurring after 2019. This pattern was not seen for other substances. While the total number of such calls remains low, the trend may continue as psilocybin use rises.
Journal of Psychoactive Drugs
August 4, 2025
Meredith C Meacham, Maha N. Mian, Ralph C. Wang et al.
2 citations
Among U.S. adults who have ever used a hallucinogen, four distinct patterns of lifetime use emerge: a group primarily using psilocybin (16%), a larger group using both LSD and psilocybin (46%), a group mainly using ecstasy (23%), and a group using multiple hallucinogens (15%). Older age is associated with higher odds of being in the LSD/psilocybin class compared with the psilocybin-only class, and non-White participants have higher odds of being in the ecstasy class. These overlapping use patterns suggest that clinical trials and future policies should account for polysubstance hallucinogen experiences.
J Psychoactive Drugs
November 10, 2025
Nicky J. Mehtani, Maha N. Mian, Gabrielle Agin-Liebes et al.
1 citation
A novel approach combines psychedelic therapy with 12-step programs to improve engagement in community-based recovery from substance use disorders. The authors argue that psychedelics may enhance openness, spiritual experiences, and social bonding, which could increase participation in 12-step meetings and practices. This accessible strategy aims to leverage existing recovery communities, potentially broadening treatment options without requiring extensive clinical infrastructure. The paper presents a theoretical framework for integrating these modalities, suggesting that such augmentation could improve outcomes for individuals with substance use disorders, though empirical evidence is not provided.
Drug and Alcohol Dependence
May 1, 2026
Juan Carlos C. Montoy, Ralph C. Wang, Allison R. Coker et al.
From 2002 to 2019, first-time use of any hallucinogen among US civilians aged 12 and older averaged 0.71% per year, with a small but statistically significant increase (odds ratio 1.009 per year). New use decreased among 12- to 17-year-olds (OR 0.96) and increased among those 65 and older (OR 1.56). LSD showed a notable rise (OR 1.08 per year), while psilocybin and MDMA did not. From 2021 to 2023, 0.79% reported new hallucinogen use, with no overall change (OR 0.97). Patterns of first-time use vary by substance and age group, with adolescents using less and older adults using more.
Current Topics in Behavioral Neurosciences
November 22, 2025
Maha N. Mian, Allison R. Coker, Grace Kretzer et al.
Communities that use psychedelics as religious sacraments have developed their own frameworks for safety and hold distinct views on risk and harm. To better understand their lived realities, researchers can collaborate closely with these communities using community-based participatory research (CBPR) practices, which center communities in co-creating research, improve engagement, build trust, and highlight local priorities. This paper presents preliminary findings from a CBPR study with entheogenic communities, sharing lessons learned from forming a community advisory board and initial pilot data gathering. Lessons include consulting community engagement experts, considerations for compensation and confidentiality, using multimodal recruitment strategies, and recognizing the unique historical context of these communities. These lessons aim to develop best practices for psychedelic research, policy, and public education.