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 Psychopharmacology
January 26, 2026
Jess Kerr-Gaffney, Samuel Myrtle, Famia Askari et al.
2 citations
A single dose of psilocybin, compared to an inert placebo, did not alter personality traits, psychiatric symptoms, or cognitive flexibility in healthy participants. However, both the 10 mg and 25 mg psilocybin groups reported greater changes in personal values at both short-term (day 8) and long-term follow-up (day 85). The acute psychedelic experience, particularly the feeling of oceanic boundlessness, partially explained these value changes, with auditory alterations also playing a role in one subscale. These exploratory findings are tentative and require replication in larger samples.
Journal of Psychopharmacology
December 26, 2025
Alice Caulfield, Allan H. Young, Mitul Mehta
2 citations
Psychedelics may produce lasting behavioral and clinical change by enhancing learning mechanisms. This narrative review synthesizes evidence across behavioral, neural, and computational levels, proposing that viewing psychedelic mechanisms through the lens of learning unifies context-dependent outcomes, increased environmental sensitivity, and neuroplastic change. Persistent changes in top-down and bottom-up information processing at a systems-level may account for both therapeutic and adverse effects, converging with the reopening of critical learning periods. This systems-level framework explains why outcomes vary widely and depend on context: the learning environment—including psychological support and therapeutic insights—shapes lasting effects. Understanding these mechanisms has translational relevance for psychedelic-assisted psychotherapy.
J Psychopharmacol
October 27, 2025
David J. Nutt, Celia Morgan, David Erritzøe et al.
2 citations
Ketamine, originally developed as an anesthetic, has emerged as a promising treatment for severe depression and other psychiatric conditions, particularly in patients who have not responded to traditional therapies. The compound can provide rapid relief from depressive symptoms, often within hours, which contrasts with conventional antidepressants that may take weeks to work. This surprising discovery has opened a new frontier in mental health treatment, offering hope for those with challenging mood disorders. However, the use of ketamine in psychiatry also raises concerns about its potential for abuse and long-term side effects, necessitating careful clinical oversight.
BJPsych Open
July 1, 2023
Allan H. Young, Wiesław Jerzy Cubała, René Ernst Nielsen et al.
2 citations
Among people with treatment-resistant depression, those who had failed three or more prior treatments were more likely to achieve remission after eight weeks of esketamine nasal spray (28.0%) than after quetiapine extended release (10.9%). For those with only two prior treatment failures, remission rates were similar between the two treatments (26.5% vs. 21.8%). Esketamine also led to faster remission in both subgroups. The results suggest esketamine may be especially effective for patients with more extensive treatment histories.
Psychotherapy and Psychosomatics
June 12, 2026
Thorsten Barnhofer, Maria Niemi, Johannes Michalak et al.
1 citation
For adults with difficult-to-treat depression—those who have not responded to prior treatments, have treatment-resistant depression, or have a chronic course—mindfulness-based cognitive therapy (MBCT) is likely superior to usual care, reducing depressive symptoms by a standardized mean difference of -0.40 at post-treatment and -0.41 at medium-term follow-up. There was a 92% and 85% probability, respectively, that these benefits exceeded a minimal important difference. However, MBCT did not show clear superiority over other active psychosocial interventions, and no robust moderators of outcome were identified across baseline severity, chronicity, or comorbidity.
Research Directions Depression
October 13, 2023
Ian B. Hickie, F. Markus Leweke, Allan H. Young
1 citation
Interest in evaluating the therapeutic value of psychedelic compounds for treatment-resistant depression has grown among research groups and the wider recreational drug-using community. This enthusiasm accompanies advocacy for decriminalization, legalization, and public licensing of these substances for medicinal use.
Biological Psychiatry
April 10, 2023
James Rucker, Mathieu Seynaeve, Allan H. Young et al.
1 citation
Nasal administration of tryptamine psychedelics significantly elevates mood in 70% of participants, based on a sample size of 150 individuals. This method enhances the effects on consciousness and psychological well-being, indicating strong potential in pharmacology and psychiatry. The study highlights how these substances influence neurotransmitter receptors, leading to altered states of awareness. With implications for forensic toxicology and drug analysis, findings suggest that psychedelics may offer new avenues for therapeutic applications in mental health.
Eur Neuropsychopharmacol
June 5, 2026
Andreas Reif, A. Elif Anıl Yağcıoğlu, Istvan Bitter et al.
No Summary
J Affect Disord
October 10, 2025
Guy M. Goodwin, Scott T. Aaronson, Oscar Alvarez et al.
correction
No Summary
BJPsych Open
June 1, 2025
Anna Borissova, Allan H. Young, Mitul A. Mehta et al.
In interviews with seven people who had previously received ketamine for treatment-resistant depression, participants were motivated by hope for symptom improvement and a desire to support depression research. They described feeling more open and involved after ketamine and thought it could enhance therapy sessions. They suggested clearer communication that mood changes may not last, providing audiovisual materials to prepare for the infusion experience, and offering check-ins between sessions plus a final session for referrals and support. These insights informed a planned feasibility randomized controlled trial comparing intravenous ketamine plus behavioral activation (n=20) against midazolam plus behavioral activation (n=20) for major depressive disorder with anhedonia.
Journal of Neurology Neurosurgery & Psychiatry
July 20, 2020
Matthew Butler, Mathieu Seynaeve, Timothy R. Nicholson et al.
Functional neurological disorder (FND) causes significant disability, yet treatment options are limited. A systematic review of nine studies from 1954–1967 involving 26 patients found that psychedelics, primarily LSD (25–2,000 mcg) and psilocybin (3–15 mg), were used alongside psychotherapy. After treatment, 69% of patients showed at least some recovery, and 23% fully recovered. Adverse events were mild and transient. Although the studies were low quality and lacked control groups, the degree of improvement suggests psychedelics may be a promising treatment for FND, warranting modern research.