The New England journal of medicine
November 3, 2022
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
1,095 citations
A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
JAMA Psychiatry
July 1, 2023
Roman Palitsky, Deanna M Kaplan, Caroline Peacock et al.
86 citations
Spiritual, existential, religious, and theological components are important in psychedelic-assisted therapy, but they have not been systematically integrated into clinical practice. Research shows that spiritually integrated psychotherapies are effective and produce additional benefits on spiritually relevant outcomes, which are particularly relevant to psychedelic therapy. Established standards in spiritually integrated psychotherapy can be applied to psychedelic-assisted therapy. Integrating these topics is needed for culturally competent, evidence-based treatment aligned with high clinical standards, and neglecting them may undermine treatment success and increase risks for patients.
Journal of Psychopharmacology
February 15, 2022
Jessica L Maples-Keller, Seth D. Norrholm, Mark Burton et al.
53 citations
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.
Journal of Psychopharmacology
July 31, 2024
Roman Palitsky, Deanna M Kaplan, John Perna et al.
32 citations
A multidisciplinary working group identified 54 potential adverse events that warrant systematic assessment in psychedelic-assisted therapies, finding that existing measurement tools substantially fail to cover these constructs. The group developed recommendations for when and how to assess these adverse events across preparation, dosing, integration, and follow-up phases, and demonstrated a preliminary assessment protocol. The framework addresses the need to capture post-acute dosing adverse events, accounting for both the pharmacotherapy and psychotherapy components of psychedelic-assisted therapy, as well as documented impacts on worldviews and spirituality.
PLoS One
January 2, 2024
Caroline Peacock, Erin Brauer, Ali John Zarrabi et al.
27 citations
Spiritual health practitioners bring unique expertise to psychedelic-assisted therapy based on their training and professional experience. Interviews with 15 such practitioners revealed seven themes in two domains: unique contributions (competency with spiritual material, awareness of power dynamics, familiarity with non-ordinary states, holding space, counterbalancing biomedical perspectives) and general contributions (using general therapeutic skills and supporting interdisciplinary collaboration). Their skills complement other clinical team members, and psychedelic-assisted therapy teams may benefit from including them. Further work is needed to define roles, qualifications, and training for these clinicians.
Journal of Mood and Anxiety Disorders
December 1, 2023
Sierra Carter, Grace Packard, Callan Coghlan et al.
18 citations
Black Americans reported more positive views of psychedelic-assisted therapy than White Americans after receiving brief psychoeducation about MDMA and psilocybin-assisted therapy. Among 294 adults (44% Black/African American or Mixed Race with Black ancestry, 56% White American; average age 36.3 years), psychoeducation increased interest and positivity across both groups. Greater depression and PTSD symptom severity was linked to higher baseline interest in both groups, and Black participants with more severe depression showed even greater interest and more positive views. The findings suggest that research groups, not potential participants, are responsible for diversifying clinical trial samples and that rebuilding trust and providing culturally attuned interventions is needed.
Psychotherapy
January 13, 2025
Roman Palitsky, Jessica L Maples-Keller, Caroline Peacock et al.
13 citations
In an open-label trial of psilocybin-assisted therapy for cancer-related demoralization and chronic pain, patients, facilitators, and caregivers identified key components and improvements for the treatment protocol. Using the Enhanced Critical Incident Technique, interviews revealed critical incidents, wish list items, and contributing factors related to therapy aspects like intention-setting and overall protocol transitions. The findings emphasize tailoring treatment to individual medical history, supporting common therapeutic factors, and ensuring collaborative care. Nine topic areas for protocol improvement emerged from the data.
Biological Psychiatry
February 15, 2025
Jessica L Maples-Keller, Laura E Watkins, Natalie Hellman et al.
12 citations
Treatment approaches for posttraumatic stress disorder (PTSD) based on fear conditioning and extinction models are reviewed. Fear extinction provides a translational model linking basic research in nonhuman animals to human treatments such as prolonged exposure therapy. Cognitive aspects of extinction, including consolidation and reconsolidation, are discussed along with behavioral and pharmacological strategies for preventing and treating chronic PTSD. Augmentation strategies reviewed include disrupting noradrenergic processes, NMDA receptor medications, physical exercise, cannabinoids, estradiol, dexamethasone, yohimbine, losartan, dopamine, and MDMA, with evidence for their efficacy in human samples. Limitations and future directions are also addressed.
Military Medicine
December 24, 2022
Joshua C. Gray, Mikela A. Murphy, Sierra Carter et al.
10 citations
Service members and veterans with traumatic brain injury and co-occurring symptoms initially held neutral views of psychedelic drugs and psychedelic-assisted therapies (PAT). After a brief psychoeducation session, their views of psychedelic drugs and interest in PAT became significantly more positive. Most participants supported making PAT available in medical settings if proven beneficial and would support a loved one engaging in PAT. The most common health concerns were long-term effects (43%), fear of losing one's mind (33%), fear of personality changes (33%), and fear of traumatic brain injury complications (24%). Logistical barriers included time, transportation, finances, work, and childcare, though 48% reported no barriers.
International review of psychiatry (Abingdon, England)
December 1, 2024
Roman Palitsky, Nicholas K. Canby, Nicholas T. van Dam et al.
6 citations
Research on adverse effects (AEs) of psychedelics has been limited, leading to underspecified profiles and potential undercounting. This article argues that meditation-related AE research, which shares phenomenological and contextual features with psychedelic AEs, offers valuable insights. An integrative review of both fields is presented, recommending that meditation AEs serve as a comparator condition. The authors propose adopting detailed, comprehensive, user-informed, impact-based, standardized, unbiased, and representative measures of AEs, along with examining factors that influence their impacts and trajectories, to advance psychedelic AE research.
Contemporary clinical trials communications
February 1, 2025
Jessica L Maples-Keller, Boadie W Dunlop, Barbara O Rothbaum
5 citations
An open-label pilot trial will test whether 100 mg of MDMA combined with massed exposure therapy—daily sessions for two weeks—is feasible for treating PTSD. The authors argue that combining MDMA with a gold-standard exposure treatment has translational support and strong dissemination potential. The study aims to enroll at least 15 adults with PTSD over two years to develop a treatment manual, which will later be tested in a randomized, placebo-controlled trial. This approach could improve the ability to treat PTSD.
March 5, 2024
Roman Palitsky, Deanna M Kaplan, John Perna et al.
4 citations
preprint
A multidisciplinary working group identified 53 potential adverse events (AEs) specific to psychedelic-assisted therapies (PATs) that current assessment tools miss. Existing measures cover only a fraction of these constructs. The group recommends new assessment methods—including patient, clinician, and informant reports—and specifies when to measure AEs across preparation, dosing, integration, and follow-up phases. The framework addresses gaps in capturing post-acute dosing effects, including changes in worldview and spirituality, which distinguish PAT from other treatments.
Psychotherapy (Chicago, Ill.)
June 1, 2026
Roman Palitsky, Laura E Captari, Jessica L Maples-Keller et al.
3 citations
The relational spirituality model (RSM) provides a framework for developing spiritual and religious competence in psychedelic-assisted psychotherapies. Psychedelic-assisted therapies can provoke personally meaningful spiritual or existential experiences linked to improved outcomes. The RSM's inclusive spiritual, existential, religious, and theological approach offers a pluralistic way to engage diverse traditions in therapy. The article describes the RSM and introduces pragmatic training methods—deliberate practice, experiential components, SERT groups, and assessment training—that can be integrated into existing mental health or psychedelic therapy training programs. It also discusses how the RSM can inform interdisciplinary collaborations across disciplines and healing communities.
Psychedelics
April 29, 2025
Ishan Pasricha, Caroline Peacock, Roman Palitsky et al.
3 citations
Spiritual health practitioners (healthcare chaplains) increasingly facilitate psychedelic-assisted therapy. A qualitative study of 15 such practitioners (60% female, average age 46.57) found two main themes: initial motivations and ongoing sources of meaning. Personal psychedelic experiences were a key initial motivator. Ongoing fulfillment came from witnessing healing in others and positive personal impacts of facilitating care. Personal experiences provide valuable firsthand knowledge of psychedelic phenomenology but may introduce bias. Training guidelines from the Association for Clinical Pastoral Education, emphasizing self-literacy and reflection, may help address these risks. The authors introduce a reflective learning exercise based on these findings.
Journal of Traumatic Stress
March 12, 2026
Leslie A. Morland, B O Rothbaum, Lauren M. Sippel et al.
2 citations
MDMA-assisted psychotherapy for PTSD shows promising results in recent randomized controlled trials, with high response and remission rates, but the FDA declined to approve it in August 2024 due to insufficient evidence. This review examines the current scientific literature on MDMA-AT, covering proposed mechanisms, methodological strengths and limitations, evidence gaps, and clinical, ethical, and regulatory issues. Key limitations include challenges with blinding, lack of active comparator conditions, no head-to-head comparisons of different therapy models, inadequate safety monitoring, and limited sample generalizability. Emerging research integrates MDMA with established trauma-focused therapies like prolonged exposure and cognitive processing therapy to leverage MDMA's effects on cognitive behavioral mechanisms.
Journal of Psychoactive Drugs
October 23, 2024
Jessica L Maples-Keller, Courtland S Hyatt, Nathaniel L Phillips et al.
2 citations
A randomized, placebo-controlled trial with 34 healthy adults examined whether a single dose of MDMA alters five-factor model personality traits and affective states 48 hours later. No statistically significant changes were observed for the four pre-registered hypotheses, but medium effect sizes emerged: trait Openness increased (d = .79) and Positive Affect increased (d = .51) compared to placebo. These preliminary findings suggest MDMA may produce short-term shifts in openness and positive mood, warranting larger, longer-term studies to clarify how such changes might inform MDMA-assisted therapy.
Psychiatry and Clinical Psychopharmacology
August 14, 2025
Nadav Liam Modlin, Jessica L Maples-Keller, Maria Sarang et al.
Among 873 people who reported trauma symptoms or a PTSD/CPTSD diagnosis, 94.8% had experienced psychological trauma and 73.4% had a formal diagnosis. Many had tried multiple medications and psychotherapies but were highly dissatisfied. Significant numbers used marijuana, psychedelics, or MDMA on their own to manage symptoms, with few physical or psychological complications. After learning about MDMA and psilocybin therapies, willingness to try them was high (0.81 and 0.83, respectively). Women and heterosexual individuals showed lower willingness, while younger and more educated respondents were more willing. The findings point to a need for further clinical research and public education about risks and harm reduction.
Psychedelic medicine (New Rochelle, N.Y.)
June 1, 2025
Sierra Carter, Grace Packard, Jessica L Maples-Keller
Black Americans are underrepresented in psychedelic trials despite high mental health needs. In four focus groups with low-income, urban Black participants, three themes emerged: informed hesitation mixed with openness; trust, autonomy, and choice; and practical solutions to improve access. Participants voiced concerns about racism in healthcare, research, drug policy, and criminalization. They emphasized building trust through community investment, autonomy, and addressing barriers like childcare and transportation. The findings support centering Black Americans' needs in psychedelic-assisted therapy to improve access and care quality.
Psychedelics.
December 17, 2024
Zachary Bosshardt, Jessica L Maples-Keller, Deanna M Kaplan et al.
Attendees at a conference on psychedelics and spiritual care generally agreed that microdosing may have benefits and expressed modest concern about potential harm from therapeutic psychedelic use. Among 178 survey respondents, 40.2% agreed or strongly agreed that psychedelics could be harmful therapeutically, while 30.7% were unsure. A subset of 32 psychedelic care facilitators reported using psychedelics to treat a wide range of diagnoses with diverse psychotherapy approaches and endorsed a need for cultural adaptations in psychedelic treatments.