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.
Neuropsychopharmacology
April 26, 2017
Robin Carhart-Harris, Guy M. Goodwin
680 citations
Plant-based psychedelics like psilocybin have ancient medicinal roots. After LSD's first English-language report in 1950, psychedelics briefly aided psychotherapy for mood disorders and alcohol dependence before prohibitive legislation in the mid-1960s halted major research. Since the early 1990s, human psychedelic research has revived, with recent reports including the first modern brain imaging study with LSD and three clinical trials of psilocybin for depressive symptoms. The authors offer opinions on the promises and pitfalls of renewed research, focusing on developing psilocybin as a depression treatment.
American Journal of Psychiatry
July 12, 2023
Guy M. Goodwin, Ekaterina Malievskaia, Gregory A. Fonzo et al.
187 citations
Psilocybin, a hallucinogen derived from mushrooms, significantly improved psychological well-being in 70% of participants in a recent drug study. Involving 100 adults undergoing therapy, those receiving psilocybin experienced enhanced emotional processing and reduced anxiety. This effect is attributed to psilocybin's influence on neurotransmitter receptors, which alters behavior and mood. Psychotherapists reported that patients showed increased openness and decreased fear of death after treatment, highlighting the potential of psychedelics like psilocybin for therapeutic use in mental health care.
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.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
September 1, 2023
Guy M. Goodwin, Megan Croal, David Feifel et al.
166 citations
A single 25 mg dose of synthetic psilocybin (COMP360) given alongside psychological support to adults with treatment-resistant depression who continued taking a selective serotonin reuptake inhibitor led to a mean reduction of 14.9 points on the Montgomery-Åsberg Depression Rating Scale at three weeks. Twelve of nineteen participants (63.2%) experienced mild treatment-emergent adverse events that resolved the same day, with no serious events or increased suicidal ideation. Response and remission occurred in 8 participants (42.1%). The authors suggest larger controlled trials are needed to determine whether this approach can benefit patients who cannot safely withdraw from antidepressants.
Translational Psychiatry
February 23, 2022
Trevor Sharp, Christopher W. Thomas, Cristina Blanco-Duque et al.
40 citations
Psilocin, a serotonergic psychedelic, alters sleep architecture and cortical activity in mice. Acute administration delays REM sleep onset, reduces NREM sleep maintenance for about three hours, and enhances a 4 Hz EEG oscillation. No long-term changes in sleep-wake quantity occur. Psilocin does not affect the overall homeostatic sleep rebound after sleep deprivation, but it slows the recovery of slow-wave activity in the medial prefrontal and surrounding cortex. These findings suggest psilocin influences both global vigilance state control and local sleep homeostasis, which may relate to its antidepressant effects.
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.
American Journal of Psychiatry
January 1, 2025
Namik Kirlic, Molly Lennard-Jones, Merve Atli et al.
27 citations
A structured framework called the Compass Psychological Support Model (CPSM) provides psychological support for individuals with treatment-resistant depression receiving investigational psilocybin treatment in clinical trials. The model aims to ensure a safe and meaningful psychedelic experience and enables future research into which aspects of psychological support or psychotherapy best complement psilocybin treatment. The authors describe therapist training, mentoring, and fidelity assessment programs developed to maintain quality and consistency in delivering the CPSM.
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.
Journal of Affective Disorders
May 1, 2023
Guy M. Goodwin, Megan Croal, Lindsey Marwood et al.
13 citations
Blinding in psychiatric clinical trials is considered ideal, but unblinding due to subjective drug effects raises concerns about demand characteristics undermining research findings. For conventional antidepressants, the strong link between dose and subjective effects does not correspond to a strong relationship with efficacy in randomized controlled trials, disproving the idea that unblinding primarily drives trial outcomes. Instead, early changes in brain function predict treatment outcomes and align with neuroscience. For psychedelic treatment of depression, unblinding is inevitable, but the therapeutic effect stems directly from serotonin receptor activation and altered brain connectivity, not just expectancy. A dose-response relationship is expected with novel mechanisms. Unblinding does not invalidate genuine recovery.
American Journal of Psychiatry
January 1, 2024
Guy M. Goodwin, Ekaterina Malievskaia, Gregory A. Fonzo et al.
12 citations
No Summary
Journal of Psychopharmacology
November 30, 2016
Guy M. Goodwin
12 citations
No Summary
Journal of Psychopharmacology
August 29, 2025
Niall M. Mcgowan, James Rucker, Rachel Yehuda et al.
10 citations
A single 25 mg dose of psilocybin, given with psychological support, was safe and well-tolerated in 22 adults with PTSD. No serious adverse events occurred, and most side effects (headache, nausea, crying, fatigue) resolved within a day. PTSD symptoms, measured by the CAPS-5 scale, showed a clinically meaningful average decrease of nearly 30 points at 4 and 12 weeks after the dose, and this improvement was linked to the intensity of the psychedelic experience. Functional impairment and quality of life also improved. The open-label design and small sample size mean further controlled trials are needed to confirm efficacy.
Neurosci Appl
January 11, 2024
Drummond E-Wen Mcculloch, Matthias E. Liechti, Kim Pc Kuypers et al.
10 citations
Psychedelic drugs like psilocybin and LSD are being tested in clinical trials for psychiatric and neurological conditions, with phase 2 studies showing particular promise for depression. At a 2023 European College of Neuropsychopharmacology meeting, experts identified key knowledge gaps that need addressing for successful medical implementation. These include understanding how these drugs work in the body (pharmacokinetics and pharmacodynamics), comparing different psychedelics, exploring the link between the duration of subjective effects and therapeutic outcomes, studying polypharmacology, and assessing the role of psychological support. The article also presents perspectives from the European Medicines Agency and Health Technology Assessors on what is most needed for medical adoption in Europe.
Journal of Psychiatric Research
December 1, 2024
Lindsey Marwood, Megan Croal, Sunil Mistry et al.
9 citations
In a phase II randomized controlled trial of 233 participants with treatment-resistant depression, those who discontinued antidepressant drugs before receiving psilocybin showed no worsening of depression severity during the discontinuation period, comparable baseline suicidality, and no compromise in psilocybin's treatment efficacy or subjective psychedelic effects relative to those who entered the trial antidepressant-free. The findings suggest that antidepressant discontinuation does not limit the feasibility of psilocybin treatment for treatment-resistant depression and support the homogeneity of psilocybin's effects as a monotherapy.
Front Hum Neurosci
June 19, 2024
Giuseppe Pasculli, Pierpaolo Busan, Eric S. Jackson et al.
5 citations
Developmental stuttering involves speech-motor disruptions linked to metabolic and network anomalies in the brain, particularly in the default mode and social-cognitive networks. These networks also influence social anxiety and avoidance, which often accompany persistent stuttering. Psychedelic compounds can modify brain metabolism and connectivity in these networks and have shown clinical benefits for conditions like depression and PTSD that share features such as rumination and social anxiety. Although no controlled trials have been conducted, anecdotal reports suggest psychedelics might alleviate stuttering and its associated symptoms. The authors argue that psychedelics warrant investigation in randomized clinical trials for developmental stuttering.
bioRxiv Preprint Server
February 16, 2021
Christopher W. Thomas, Cristina Blanco-Duque, Benjamin J. B. Bréant et al.
4 citations
preprint
A single dose of psilocin, the active compound in psychedelic mushrooms, alters sleep architecture in mice. Psilocin delayed the onset of REM sleep and reduced NREM sleep maintenance for about three hours after injection, without causing long-term changes in sleep quantity. The acute brain response featured enhanced oscillations around 4 Hz. When mice were sleep-deprived, psilocin did not change the overall amount of sleep rebound, but it slowed the recovery of slow wave activity in the medial prefrontal cortex. These findings suggest that psilocin affects both global vigilance and local sleep homeostasis, which may relate to its potential antidepressant effects.
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.
EClinicalMedicine
December 1, 2025
Nadav Liam Modlin, Victoria Williamson, Guy M. Goodwin et al.
2 citations
Psilocybin treatment for post-traumatic stress disorder, when delivered with standardized preparation and support, may allow patients to engage with trauma-related material indirectly through affective, somatic, and self-transcendent experiences, such as feelings of unity or dissolution of self, rather than requiring direct confrontation with traumatic memories as in standard therapies. This qualitative study, nested within a phase 2 trial involving 21 adults with PTSD, identified four core themes: non-pharmacological factors for psychological safety and trust, the experiential nature of psilocybin treatment, engagement with trauma-related material, and comparative reflections on prior therapies. The findings suggest psilocybin offers a meaningful therapeutic opportunity, but larger controlled studies are needed.
European Psychiatry
March 1, 2023
Guy M. Goodwin, Lindsey Marwood, S. Mistry et al.
1 citation
A single dose of COMP360 psilocybin 25mg, a synthetic form of psilocybin, rapidly improved symptoms of depressed mood and anhedonia in adults with treatment-resistant depression, compared with a 1mg dose. Improvements were apparent by the day after administration and lasted up to 12 weeks for some symptoms. At Week 3, the largest differences on the clinician-rated MADRS scale were for Inability to Feel, Apparent Sadness, Lassitude, and Reported Sadness; on the self-rated QIDS-SR16, the largest difference was for Feeling Sad. The 10mg dose showed intermediate effects, suggesting a dose-related response.
Journal of Psychopharmacology
July 16, 2026
Robert F. Dougherty, Nadav Liam Modlin, Niall M. Mcgowan et al.
In a 12-week clinical trial of 25 mg COMP360 psilocybin for 22 participants with post-traumatic stress disorder, audio recordings showed that during drug-administration sessions speech by either party was rare: silence filled 78% of the time on average, compared to 25% to 30% in non-administration sessions. Thematic analysis of post-dosing interviews revealed that support was minimally enacted but experientially salient, autonomy was promoted through the introspective state and non-directive support, and primary modes of support during altered states included reassurance and validation. The minimal verbal interaction distinguishes this monitoring and support from conventional psychotherapies and MDMA-assisted therapy.
Journal of Clinical Psychopharmacology
December 9, 2025
Namik Kirlic, Merve Atli, Sunil Mistry et al.
In people with treatment-resistant depression who received a single dose of 25, 10, or 1 mg of COMP360 psilocybin, the drug dose was the strongest and most consistent predictor of the subjective psychedelic experience. Some pretreatment characteristics—such as positive affect, lower generalized anxiety symptoms, higher executive functioning, and greater personality disorder symptoms—had weak effects on different aspects of the experience. These findings suggest that pretreatment clinical characteristics are not major determinants of the acute psychedelic experience; dose remains the largest driver.
J Affect Disord
October 10, 2025
Guy M. Goodwin, Scott T Aaronson, Oscar Alvarez et al.
correction
No Summary