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Journal articleStoliker D, Novelli L, Khajehnejad M, et al., 2026,
Psychedelics align brain activity with context.
, NaturePsychedelics can profoundly alter consciousness by reorganizing brain connectivity1,2, producing acute experiences that shape lasting psychological change3,4. Psychedelic dynamics are commonly described as desynchronized or entropically disordered5,6, yet the brain organization underlying self-dissolving and boundary-dissolving experiences that participants often report7, and how context shapes that organization8, remain unresolved. To address this, we acquired the largest single-site psychedelic neuroimaging dataset to date. Sixty-two adults underwent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) during rest and naturalistic stimuli (meditation, music and movie), before and on the day of psilocybin administration (fMRI ~ 80 min post-dose; EEG ~ 150 min post-dose). Half ranked the experience among the most meaningful of their lives7. Here, using machine learning to represent the brain dynamics of each individual as low-dimensional trajectories, we show that psilocybin reorganizes brain activity into structured, context-sensitive patterns that co-vary with the quality of subjective experience, revealing a latent order missed by time-averaged measures. Networks that ordinarily segregate internal and external processing integrated, producing cohesive context-aligned trajectories in participants reporting the felt experience of being continuous with, rather than separate from, the environment, a state we refer to as embeddedness. The strength of this context alignment scaled with both the depth of self-dissolving and boundary-dissolving experience and the next-day mindset change. Our findings recast apparent disorder as latent organization aligned with context, linking neurobiology to subjective experience and behavioural change.
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Journal articleOstrand AE, Nour MM, Timmermann C, et al., 2026,
Defining 'psychedelic'.
, J PsychopharmacolHumphry Osmond coined the term 'psychedelic' in 1956, conjoining 'psyche' for 'soul' and 'delic' for 'to manifest' or 'illuminate'. Soul-illumination is a compound noun that describes a psychological state or process. Osmond intended for it to be a taxonomic noun-naming, not just a state-but a category of drug that can induce this psychological effect as its principal action. Consistent with the etymology of psychedelic, the present work respects the fundamental importance of phenomenology. Accordingly, we examine the main subjective effect of three different psychoactive drugs, psilocybin, ketamine, and MDMA (3,4-methylenedioxymethamphetamine) (variable label, Drug). Over 200 participants rated Delphi-generated subjective rating scale items based on their personal experiences with all 3 drugs. Factor analyses revealed three or four sufficiently independent dimensions of subjective experience (variable label, Effects). A machine-learning classifier successfully predicted Drug from Effects, validating the hypothesis that psilocybin, ketamine and MDMA have categorically distinct subjective effect profiles, differentiable by (1) visions and psychological insight (psilocybin), (2) dissociation (ketamine) and (3) pro-social and loving feelings (MDMA). We conclude that psilocybin is an exemplar psychedelic-a category of drug definable by the induction of a psychedelic state. The quintessential psychedelic phenomenon is a subjective state characterized by visions and psychological insight.
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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 articleAgnorelli C, Peill J, Sawicka G, et al., 2026,
Detecting neuroplastic effects induced by ketamine in healthy human subjects: A multimodal approach.
, J Cereb Blood Flow Metab, Vol: 46, Pages: 2125-2137We investigated ketamine's neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and resting-state fMRI (intrinsic brain activity, functional connectivity), before and after ketamine. While group-level analyses showed no significant increases in PET synaptic markers, ketamine administration resulted in significantly elevated glutamate levels within the anterior cingulate cortex (ACC). Functional connectivity analyses revealed reduced coupling between the ACC and the dorsolateral prefrontal cortex (dlPFC) and increased coupling between the ACC and the amygdala in the days following ketamine administration. Our multimodal analysis revealed that participants showing an increase in [11C]-UCBJ volume distribution (VT), a putative index of synaptic plasticity, showed a correlated reduction in intrinsic activity within regions belonging to the default mode network (DMN). By linking molecular, cellular and network-level changes, our results point to the DMN as a central hub where ketamine may reshape brain hierarchies in the long term, providing new directions for understanding its therapeutic mechanisms and developing targeted treatments.
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Journal articleBailey NW, Webb SL, Fitzgibbon BM, et al., 2026,
No evidence for deleterious effects of psilocybin and MDMA on working memory or related neurophysiological activity in a non-clinical population: An uncontrolled exploratory study.
, J PsychopharmacolBACKGROUND: Research indicates psychedelics hold therapeutic potential, but possible deleterious effects have been insufficiently examined. We explored working memory (WM) performance and WM-related neurophysiological activity before and after exposure to psilocybin or 3,4-methylenedioxymethamphetamine (MDMA) in an uncontrolled study. METHODS: Healthy participants were exposed to a single dose of psilocybin or MDMA (data analysed from 29 participants for each drug, with 16 receiving both drugs after >3-month washout). One to 16 days before and 5-16 days after dosing, participants completed a 3back WM task and eyes-closed resting with electroencephalography (EEG), plus a 3back during a 3-month remote follow-up. RESULTS: After dosing, both groups showed increased alpha to gamma WM-related oscillatory power (p < 0.001). After psilocybin, participants showed steeper WM-related aperiodic slopes (p = 0.018), an effect maximal in occipital electrodes (p < 0.001, Cohen's d = 0.802, BF10 = 155.138), and significant in occipital electrodes during resting (p = 0.008). The MDMA group showed improved task accuracy in the post-dosing EEG session (p = 0.005, Cohen's d = 0.561, BF10 = 7.809). Both groups showed improved accuracy at 3-months (p-holm < 0.001, Cohen's d = 0.678, BF10 = 272.074). CONCLUSIONS: Our results are suggestive of enduring neurophysiological effects following a single dose of MDMA or psilocybin. Our results do not support concerns about cognitive impairments from single exposures to MDMA or psilocybin in controlled settings, suggesting clinical utility does not risk impairing WM. However, given the uncontrolled study design, future research is required to confirm our observations reflect drug-induced neurophysiological changes.
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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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