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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 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 articleVamvakopoulou IA, Nicholls D, Nutt DJ, et al., 2026,
Exploring new avenues: Psychedelic-assisted therapy for young people.
, Br J Clin PharmacolRates of mental illness in young people are increasing, whereas the development of novel mental health treatments has not significantly progressed. Psychedelic-assisted therapy, using substances such as psilocybin and 3,4-methylenedioxymethamphetamine (MDMA), has shown potential in the treatment of mental illnesses in the adult population, including depression, anxiety and post-traumatic stress disorder. Interest has been growing around the potential use of psychedelic-assisted therapy to treat mental illness in adolescents. We present here a comprehensive review of all research focusing on children and young people, from experimental research of the 50s to observational and retrospective research focusing on traditional and Western non-medical use. The limited available research so far suggests that psychedelics appear to be safe overall and may have the potential to improve mental wellbeing in young people. However, young people may be at more risk of experiencing anxiety, challenging experiences and ego dissolution, but more thorough clinical research is warranted. Moving forward, we suggest that psychedelic-assisted therapy for young people should be administered within a rigorous ethical framework, where education of both the young people and their families is incorporated. Family involvement should be considered as part of the therapeutic framework. Lastly, avenues within the psychedelic space should be considered for young people, like the use of lower doses (psycholytic approach), which might lower the potential risks that are seen with high doses.
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Journal articleCarhart-Harris R, 2026,
Human brain changes after first psilocybin use
, Nature Communications, Vol: 17, ISSN: 2041-1723Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown. In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes are detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being are seen at one-month. Diffusion tensor imaging (DTI) done before and one-month after 25mg psilocybin reveals decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlate with decreases in brain network modularity (fMRI) over the same month. Enduring functional brain changes are largely absent, but network modularity change (numerical decrease) negatively correlates with well-being change (significant increase), in line with previous findings in depression. Increased cortical signal entropy (EEG) at 1- and 2-hours post-dosing predicts improved psychological well-being at one-month. Next-day psychological insight mediates the entropy to well-being relationship. All effects are exclusive to 25mg psilocybin; no effects occur with a 1mg psilocybin placebo.
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Journal articleSimonsson O, Lyons T, Marks J, et al., 2026,
Effects of psychedelic use on authoritarian attitudes revisited.
, J PsychopharmacolBACKGROUND: Previous research suggests that psychedelics may, under certain conditions, decrease authoritarian attitudes, but larger and more rigorously designed studies are needed to confirm these findings. AIMS: We aimed to examine the effects of psychedelic use on authoritarian attitudes. METHODS: Using data from three separate studies with different designs and populations, we investigated the relationship between psychedelic use and authoritarian attitudes. Study 1 was a naturalistic observational study with participants who planned to use psychedelics at their own initiative, Study 2 was a single-arm study with healthy volunteers who received psilocybin, and Study 3 was a randomized, controlled trial with patients diagnosed with depression who received psilocybin or escitalopram. RESULTS: Across the three studies, results showed no significant changes in authoritarian attitudes after psychedelic use. CONCLUSIONS: Contrary to previous research, the latest evidence is not compelling that psychedelic use influences authoritarian attitudes in a reliable direction. Future research should recruit larger and more diverse samples, collect additional context-related data, and also investigate political outcomes other than authoritarian attitudes.
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Journal articleAli SS, Carhart-Harris RL, Sieg KG, 2026,
Classic psychedelics in obsessive–compulsive disorder: a circuit-based framework
, Nature Mental Health, Vol: 4, Pages: 540-550Obsessive–compulsive disorder (OCD) is a psychiatric condition with high rates of treatment resistance. Emerging neuroimaging evidence implicates dysfunction in large-scale brain networks, particularly the cortico–striatal–thalamo–cortical (CSTC) circuit, default mode network (DMN) and salience network (SN). Lysergic acid diethylamide (LSD) and psilocybin induce acute dysregulation of the DMN and increase connectivity across normally segregated networks, potentially disrupting maladaptive rumination and self-referential loops. Furthermore, psychedelics may improve aberrant DMN–SN connectivity in OCD, improving functioning under the triple network model. Simultaneously, both LSD and psilocybin modulate CSTC function, particularly by modulating activity in the subthalamic nucleus and striatum, regions implicated in compulsive behavior. Beyond network disruption, psychedelics rapidly enhance neuroplasticity via 5-HT<inf>2A</inf>-receptor-mediated pathways, promoting dendritic spine formation (rodents). These dual mechanisms may ‘reset’ pathological patterns and support long-term restructuring of maladaptive circuits. Future clinical trials with specific neuroimaging endpoints are needed to validate the presented framework for psychedelic action in OCD.
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Journal articleGirn M, Doss MK, Roseman L, et al., 2026,
An international mega-analysis of psychedelic drug effects on brain circuit function.
, Nat Med, Vol: 32, Pages: 1543-1554Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and a Bayesian hierarchical modeling framework, we discovered several common features in the induced alterations to brain function across drugs and sites. Most prominently, we identified a core signature of increased functional connectivity between transmodal (default, frontoparietal and limbic) and unimodal networks (visual and somatomotor), with subnetwork specificity. Furthermore, key subcortical regions (thalamus, caudate and putamen) and the cerebellum exhibited altered coupling with sensorimotor networks. In contrast to several single-site reports, Bayesian modeling revealed weak-to-moderate and selective reductions in within-network functional connectivity, with substantial variability across drugs and networks. Together, these findings extend past work by demonstrating that psychedelics reconfigure large-scale cortical organization while selectively engaging subcortical circuitry. This study provides the most comprehensive synthesis of psychedelic brain action to date, helping resolve inconsistencies and offering a probabilistic map of how psychedelics alter large-scale brain organization. We hereby provide a cornerstone to benchmark and shephe
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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 MetabWe 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 articleNewson M, Roseman L, Haslam SA, 2026,
Towards social curative psychedelic treatment.
, Discov Ment Health, Vol: 6 -
Journal articleAgnorelli C, Garling HD, Paterson LM, et al., 2026,
Recent advances in PET measures of brain 5-HT release.
, J Cereb Blood Flow MetabSerotonin (5-hydroxytryptamine, 5-HT) is a neuromodulator underpinning various psychological and physiological processes, with dysregulation implicated in numerous psychiatric disorders. Non-invasive measurement of endogenous 5-HT release in the living human brain is essential to advance understanding of the serotonergic system. The combination of Positron Emission Tomography (PET) neuroimaging of serotonergic receptors with pharmacological and behavioural challenges that stimulate endogenous 5-HT release, offers a unique approach to quantify 5-HT dynamics in vivo. In 2010, Paterson and colleagues concluded in a thorough review that measures of 5-HT release were constrained by limitations in the sensitivity of available tracers and potency of pharmacological challenges. Novel tracers combined with optimised pharmacological challenge paradigms have demonstrated sensitivity to changes in endogenous 5-HT, enabling reproducible detection of acute 5-HT release in both preclinical and human studies in the last 15 years of research. These include the use of agonist radioligands with preferential binding to high-affinity receptor states, such as [11C]AZ10419369 and [11C]Cimbi-36, antagonist tracers, such as [18F]Altanserin, refined challenge designs using pharmacological 5-HT releasers, such as fenfluramine and amphetamine, and the integration of hybrid PET/MR imaging to assess neurovascular aspects. These advances have shifted the field from questioning feasibility to addressing optimal strategies for measuring serotonergic dynamics.
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