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
February 6, 2013
Jonathan Posner, David J Hellerstein, Inbal Gat et al.
275 citations
People with dysthymic disorder (DD) show greater coherence of neural activity within the brain's default mode network (DMN) compared with healthy controls, similar to abnormalities seen in major depressive disorder. In a 10-week double-blind, placebo-controlled trial of duloxetine, treatment with duloxetine normalized DMN connectivity, while placebo did not. The findings suggest increased DMN connectivity may be important in the pathophysiology of depressive illness, and its normalization may be a causal pathway through which antidepressants reduce depression.
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.
Psychopharmacology
January 13, 2022
David A Bender, David J Hellerstein
82 citations
A review of studies since 1991 identified 14 clinical trials of classical psychedelics—11 of psilocybin (257 participants), 1 of LSD (12 participants), and 2 of ayahuasca (46 participants). Published studies largely support the hypothesis that small numbers of treatments with psychedelic-assisted psychotherapy can offer significant and sustained alleviation of symptoms for multiple psychiatric conditions. No serious adverse events attributed to psychedelic therapy have been reported. Existing studies have limitations including small sample sizes, difficulty in blinding, limited follow-up, and highly screened treatment populations. The ideal means of employing these substances to minimize adverse events and maximize therapeutic effects remains controversial.
Journal of Psychiatric Research
May 1, 2023
Franklin R. Schneier, Jamie D. Feusner, Michael G. Wheaton et al.
79 citations
A single 25 mg oral dose of psilocybin, given with psychological support, significantly reduced body dysmorphic disorder (BDD) symptoms in 12 adults whose condition had not responded to at least one prior serotonin reuptake inhibitor. Over 12 weeks of follow-up, scores on a standard BDD severity scale decreased substantially, with a large effect size and improvements evident from week 1 and sustained through week 12. Seven of 12 participants (58%) showed a 30% or greater reduction in symptoms at week 12. No serious adverse events occurred. These preliminary findings suggest psilocybin may be a promising treatment for BDD, warranting further controlled trials.
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.
Psychopharmacology
August 22, 2023
Robert F. Dougherty, Patrick Clarke, Merve Atli et al.
21 citations
A machine learning model that analyzes language from therapy sessions can predict which patients with treatment-resistant depression will respond to psilocybin therapy. Researchers used a zero-shot classifier based on the BART large language model to measure sentiment (valence and arousal) in transcripts of therapist-patient conversations one day after COMP360 psilocybin administration. These sentiment scores, combined with the Emotional Breakthrough Index and treatment arm, were fed into multinomial logistic regression models. The models predicted responder status at week 3 and through week 12 with 85% and 88% accuracy, respectively, and AUC values of 88% and 85%. This approach could enable early identification of patients needing alternative treatments.
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.
American Journal of Psychotherapy
May 6, 2025
David A Bender, Sandeep M. Nayak, Joshua S. Siegel et al.
7 citations
Practitioners of psychedelic therapy largely view physical touch as an important component of treatment, but they also emphasize strict professional boundaries and the necessity of patient consent. In a survey of 40 practitioners who had overseen an average of 41.4 psychedelic sessions, 70% agreed that therapeutic touch is crucial. However, most deemed specific forms of touch inappropriate: 63% considered bodywork inappropriate, and 98% considered full-body contact inappropriate. Free-response analysis showed 96% supported touching the patient's hand and 58% supported touching the shoulder. Unprompted, 63% of respondents stressed the importance of consent. These views may inform future practice.
Psychedelics.
September 24, 2024
Xi Zhu, Chen Zhang, David J Hellerstein et al.
6 citations
A single 25 mg dose of psilocybin, given with psychological support, led to significant reductions in body dysmorphic disorder symptoms at one week and twelve weeks after dosing in eight adults with moderate-to-severe nondelusional BDD. Resting state functional connectivity measured one day after dosing showed increased connectivity within the Executive Control Network and between the Executive Control Network, Default Mode Network, and Salience Network. These connectivity increases predicted symptom improvement at one week. The authors note the small sample size and uncontrolled design require larger controlled studies to validate the findings.
The Journal of Clinical Psychiatry
February 5, 2025
David A Bender, Sandeep M. Nayak, Joshua S. Siegel et al.
3 citations
Practitioners who oversee psychedelic therapy sessions slightly prefer an 'emotive' approach—one that emphasizes human and spiritual elements—over a 'neuromodulatory' approach that focuses on biological drug effects. A survey of 40 qualified respondents from at least 4 countries, 11 U.S. states, and 16 institutions found no consensus on many psychological support strategies. Four key themes emerged: the importance of trust, the role of spirituality, creating an emotional setting, and conceptualizing negative experiences. Practitioners trained at the Multidisciplinary Association for Psychedelic Studies or the California Institute of Integral Studies showed a significantly stronger emotive preference than those trained elsewhere.
September 30, 2022
Robert F. Dougherty, Patrick Clarke, Merve Alti et al.
3 citations
preprint
A machine learning model that analyzes language from therapy sessions accurately predicted which patients with treatment-resistant depression would respond to psilocybin treatment. Transcripts of psychological support sessions held one day after COMP360 (a synthetic psilocybin formulation) administration were analyzed using a zero-shot classifier based on the BART large language model to measure sentiment (valence and arousal) for both participant and therapist. These scores, combined with the Emotional Breakthrough Index and treatment arm, were used to predict treatment outcome measured by MADRS scores. Two multinomial logistic regression models predicted responder status at week 3 and through week 12 with 85% and 88% accuracy, and AUC values of 88% and 85%, respectively. The approach enables rapid prognostication of personalized response to psilocybin treatment and insights into therapeutic model optimization.
Journal of Affective Disorders
August 1, 2026
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.
BJPsych Open
February 12, 2026
David A Bender, Holly Dunn, Amanda Pekau et al.
1 citation
From 2000 to 2025, media coverage of psychedelic drugs increasingly focused on their therapeutic potential, rising from 13.3% of articles in 2000–2009 to 85.3% in 2020–2025. Overall sentiment was positive, with an average score of 78.5 out of 100. However, negative and neutral coverage has grown since 2020: the proportion of articles with sentiment scores of 65 or below rose from 3.6% in 2020 to 20.9% in 2024, and average sentiment dropped significantly in 2024 compared to 2020–2023. Artificial intelligence sentiment ratings closely matched human ratings.
Psychopharmacology
October 27, 2025
David A Bender, Sandeep M. Nayak, Joshua S. Siegel et al.
Providers administering psychedelic drugs in clinical trials report a range of challenges, including intense dysphoria during sessions (42% of respondents), disappointment with the intervention (25%), and re-engaging with traumatic experiences (17%). An anonymous survey of 40 qualified respondents who oversaw 1656 psychedelic sessions identified 11 distinct themes of challenges. 70% of respondents felt that individuals with PTSD or prior trauma need additional psychological support, and they recommended an average of 9.8 hours of total psychological support for first-time recipients with serious mental illness. These findings highlight the need to incorporate potential adverse experiences into psychological support protocols for clinical trials and future guidelines.
J Affect Disord
October 10, 2025
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
correction
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