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
August 31, 2023
Charles L Raison, Gerard Sanacora, Joshua Woolley et al.
493 citations
A single 25-mg dose of synthetic psilocybin, administered with psychological support, produced a clinically significant and sustained reduction in depressive symptoms and functional disability over 43 days in adults with major depressive disorder. In a phase 2 trial of 104 participants, those receiving psilocybin showed a mean 12.3-point greater improvement on the Montgomery-Asberg Depression Rating Scale at day 43 compared with those receiving a niacin placebo. Psilocybin also improved daily functioning and led to more sustained response, though not remission. No serious adverse events occurred, but psilocybin was associated with more overall and severe adverse events.
Journal of Affective Disorders
February 3, 2023
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
168 citations
Three weeks after a single dose, 25 mg of psilocybin, and to a lesser extent 10 mg, improved patient-reported measures of depression severity, anxiety, affect, and functioning in people with treatment-resistant depression. These findings extend the primary results from the largest randomized clinical trial of psilocybin for TRD, highlighting outcomes that matter to patients.
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 affective disorders
March 1, 2025
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
35 citations
In treatment-resistant depression, a single dose of 25 mg of psilocybin produced stronger correlations between certain psychedelic experiences and depression improvement three weeks later than lower doses. The intensity of psychedelic effects was dose-related, but scores for different doses overlapped considerably. At the 25 mg dose, dimensions of oceanic boundlessness and visual restructuralization, along with emotional breakthrough, showed the strongest correlations with reduced depression scores. The study does not establish causation and requires replication. The overlap in experience intensity across doses suggests unblinding to dose is less likely. Correlations between psychedelic experience and outcome indicate specificity in psilocybin's mechanism of action.
Brain Sciences
February 6, 2025
Michael J Lucido, Boadie W Dunlop
15 citations
Non-response to initial depression treatments is common and harmful. A systematic search of US and EU clinical trial registries identified 50 trials for treatment-resistant depression, 20 for anhedonia, and 25 for suicide. Glutamate system modulation is the mechanism with the most compounds in development, including NMDA and AMPA receptor modulators. Psychedelics, especially psilocybin, have seen the greatest surge in recent years. Other mechanisms include GABA, monoamine, anti-inflammatory, and orexin modulators. Challenges for detecting efficacy include population heterogeneity, comorbid disorders, psychosocial stressors, and prior medication effects.
The Journal of clinical psychiatry
March 3, 2025
Guy M Goodwin, Ania Nowakowska, Merve Atli et al.
14 citations
A single 25 mg dose of the synthetic psilocybin formulation COMP360 showed a longer time before depressive events recurred over 52 weeks compared with 1 mg and 10 mg doses in people with treatment-resistant depression. In the full group of 233 participants, the median time to a depressive event was 92 days for the 25 mg group, 83 days for the 10 mg group, and 62 days for the 1 mg group. Most participants had a depressive event by 12 weeks. Adverse events were rare; one case of mild suicidal ideation in the 1 mg group was considered possibly related to the drug. Larger long-term studies are needed to confirm these results.
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.
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.
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.