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.
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.
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.
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.
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 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.
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
The International Journal of Neuropsychopharmacology
August 1, 2025
Guy M. Goodwin
A single 25-mg dose of synthetic psilocybin (COMP360) produced larger and more durable reductions in depression severity than a 1-mg control in adults with treatment-resistant depression. Dose-dependent improvements on the Montgomery-Asberg Depression Rating Scale were evident from day 2, remained statistically significant through week 6, and were numerically still present at week 12. The intensity of the psychedelic experience, particularly feelings of boundlessness, was linked to better clinical outcomes. Over 90% of adverse events were mild or moderate. The findings suggest COMP360 may become a useful treatment for treatment-resistant depression, though suicidality remains a concern.
World Psychiatry
September 15, 2023
Guy M. Goodwin
Psilocybin, once metabolized to psilocin, activates 5-HT2A receptors, enhancing cortical GABA function and brain connectivity. The largest randomized controlled trial of psilocybin in treatment-resistant depression (COMP 001) showed a dose-effect relationship: 25 mg of COMP360 produced significantly greater reduction in depressive symptoms than 1 mg at 3 weeks, with 10 mg intermediate. The psychedelic experience is variable, making unblinding unlikely to explain results. Psychological support—preparation, minimal guidance during the session, and integration—differs from psychotherapy, and mood improvement was evident the day after drug administration, before integration. The author argues psilocybin's antidepressant effect is primarily drug-driven, not psychotherapeutic.
Neuroscience Applied
January 1, 2023
Guy M. Goodwin, Megan Croal, J. Chai-Rees et al.
No Summary