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Journal articleGoodwin GM, Aaronson ST, Alvarez O, et al., 2026,
The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression: A post hoc path analysis.
, J Affect Disord, Vol: 406INTRODUCTION: The contribution of patient support to psilocybin's antidepressant effects remains uncertain. METHODS: Relationships between therapeutic alliance (Scale to Assess Therapeutic Relationship-Patient version; STAR-P), psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire and Emotional Breakthrough Inventory; 5D-ASC and EBI) and clinical outcomes (Montgomery-Åsberg Depression Rating Scale; MADRS) were explored using correlation and path analysis for individuals with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support (N = 79). RESULTS: Change from Baseline to Week 3 MADRS scores showed weaker correlations with pre-dosing therapeutic alliance (-0.178) than with measures of the psychedelic experience: EBI (-0.637), Oceanic Boundlessness (-0.508), and Visual Restructuralization (-0.516). Path analysis showed no nominally significant direct effects of therapeutic alliance on Week 3 MADRS scores, but there were nominally significant effects of therapeutic alliance on psychedelic experience (Oceanic Boundlessness (β = 0.28), Visual Restructuralization (β = 0.27), and Auditory Alterations (β = 0.25)). Only one indirect effect of therapeutic alliance on clinical outcome reached nominal significance (via Visual Restructuralization; β = -0.15). Stronger effects were seen on clinical outcomes for psychedelic experience (EBI (β = -0.59), Oceanic Boundlessness (β = -0.53), Visual Restructuralization (β = -0.54), and Auditory Alterations (β = -0.24)). CONCLUSIONS: The therapeutic alliance appeared to facilitate the psychedelic experience, and these experiences in turn had stronger nominally significant direct effects on clinical outcomes. The effects of the alliance itself on therapeutic efficacy were either limited or absent. TRIAL REGISTRATION: EudraCT number: 2017
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Journal articleCarhart-Harris RL, Rosenblat JD, 2026,
Psychedelics Trials and Outcomes-A Closer Look.
, JAMA Psychiatry -
Journal articleDouglass HM, Spriggs MJ, Godfrey K, et al., 2026,
Psilocybin therapy for adult females with anorexia nervosa: pilot study.
, Br J Psychiatry, Pages: 1-9BACKGROUND: Anorexia nervosa is a debilitating eating disorder with high mortality and chronicity rates owing to the paucity of effective existing treatments. Several clinical trials using psilocybin therapy have demonstrated therapeutic efficacy and safety in psychiatric conditions, including anorexia nervosa. AIMS: This study aimed to further assess the safety, feasibility and potential efficacy of psilocybin therapy in anorexia nervosa. METHOD: This single-blind, within-individual pilot study recruited 21 females with anorexia nervosa, who underwent three dosing sessions with oral psilocybin (COMP360) over 6 weeks in a fixed order (1 mg, 25 mg, 25 mg), alongside talk therapy and adjunctive to treatment as usual. Adverse events were monitored throughout the study. Primary clinical outcome measures were global Eating Disorder Examination Interview (EDE) and Readiness and Motivation Questionnaire (RMQ) precontemplation scores. Primary time points for the EDE were the 6-week final visit, 3-month follow-up and 6-month follow-up; and for the RMQ, they were the 6-week final visit and comparison between dosing days. Global EDE Questionnaire scores were a key secondary outcome. Key time points were the 6-week final visit and comparison between dosing days. There was a 12-month remote follow-up. RESULTS: Psilocybin was well tolerated by all participants. The most common adverse events were headache, nausea and dizziness. Two serious adverse events (suicide attempts) were reported for one participant within the 6-12-month period. Relative to baseline, participants displayed significant improvements in their eating disorder symptoms (EDE scores: p < 0.0001, d = 0.98, 6 months) and motivation to change (RMQ scores: p = 0.0017, d = 0.65, 12 months). However, there was a large variation in improvement and maintenance during the follow-up. CONCLUSIONS: This study further provides preliminary support for the feasibility, safety and potential efficacy of this intervention to tr
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Journal articleRoseman L, 2026,
Micro-Messiahs and the Revolutionary Dynamics of Psychedelic Diffusion
, Religions, Vol: 17Prophetic or messianic states of consciousness are charged with moral urgency and are active, historical, political, and sometimes infused with ego. In this paper, I inquire into psychedelic micro-messianic phenomenology and revolutionary dynamics through the historical case studies of Allen Ginsberg, Master Irineu, and John Wilson (Moonhead)—figures associated with the diffusion of LSD, Daime (ayahuasca), and peyote, respectively. I propose that, in moments of tension and uncertainty, psychedelics can catalyse micro-messianic movements through which these substances diffuse into new situations. A revelatory event motivates the subject, in fidelity to the event, to spread the substance and practice. Through the innovation, a movement emerges until it is routinised or inverted. A new status quo then stabilises, from which another revelatory event may arise. Through these historical cases, I offer a detailed analysis of such revolutionary dynamics, drawing on various theoretical perspectives (Weber, Wallace, Kuhn, Taves, Whitehouse, Rogers, Badiou, and others). In doing so, I demonstrate how psychedelic insights and actions are intertwined, and how psychedelic revelations seek to ripple outward into movements.
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Journal articleNutt DJ, 2026,
Farewell to Jim Watson (and Francis Crick). A reflection on their contributions to psychiatry and brain science.
, J Psychopharmacol, Vol: 40, Pages: 993-994 -
Journal articlePasquini L, Vohryzek J, Escrichs A, et al., 2026,
Modeled Long-Term Effects of Psilocybin on Dynamic Activity and Effective Connectivity of Fronto-Striatal-Thalamic Circuits.
, Hum Brain Mapp, Vol: 47Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we performed secondary analyses and applied computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naïve healthy volunteers. We first showed that dynamic FST activity increased 4 weeks after a full dose of psilocybin. We then proceeded to mechanistically account for these changes by providing tentative model-based support that reductions in the structure-function coupling contribute to increased dynamic FST activity postpsilocybin. Finally, we used computational approaches to show that psilocybin induces longitudinal increases in bottom-up and reduced top-down modulation of FST circuits. We then used publicly available receptor maps to show that cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, while increased information outflow via subcortical and limbic regions relates to local D2 receptor availability. Together, these findings suggest that increased FST flexibility weeks after a high dose of psilocybin is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism contributing to the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia nervosa.
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Journal articleCarhart-Harris RL, 2026,
The entropic brain today.
, BrainIntroduced in 2014 and revised in 2018, the entropic brain hypothesis has accrued a wealth of supportive evidence. The hypothesis states that-along a dimension of the size of phenomenal consciousness-expansive states reliably exhibit increased brain entropy whereas the inverse applies for states of no or reduced consciousness. Examples of expansive states include expert meditation, flicker light stimulation, near-death-like experiences, atypical breathing, rapid-eye-movement sleep, the pre-ictal aura, unmedicated early psychosis and psychedelic drug states. Examples of states of no or reduced consciousness with low brain entropy, include disorders of consciousness, deep sleep, the anesthetized state, seizure, post-stroke, ageing, cognitive impairment, and neurodegenerative illness. It is shown that the entropic brain has convergent, correlative, predictive, discriminative and external validity. Regarding its predictive validity, increased brain entropy under psilocybin (in a supportive context) predicts subsequent improvements in mental health (improved wellbeing 1-month post-dose). Regarding its discriminative validity, changes in brain entropy selectively index the breadth of subjective experience versus alternative dimensions, such as arousal. Regarding portability/external validity, an entropy-related function is applied in generative artificial intelligence. In conclusion, the entropic brain is a useful model of conscious states.
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Journal articleReid MJ, Kettner H, Blanken TF, et al., 2026,
Correction to: Preliminary Evidence of Sleep Improvements Following Psilocybin Administration, and their Involvement in Antidepressant Therapeutic Action.
, Curr Psychiatry Rep, Vol: 28 -
Journal articleAday JS, Carhart-Harris RL, Boehnke KF, 2026,
Blunted Psychedelic Drug Effects in Older Adults.
, Am J Geriatr Psychiatry, Vol: 34, Pages: 873-876 -
Journal articlePasquini L, Girn M, Kettner H, et al., 2026,
Neural correlates of insight on psilocybin: a within-subjects, healthy volunteer study
, JoCN Forum
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