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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, 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 articleTabaac BJ, Carhart-Harris RL, Yung T, 2026,
Clinical improvement following an integrative iboga microdosing protocol in post-concussive and hypoxic brain injury syndromes: a case series
, Frontiers in Pharmacology, Vol: 17<jats:sec> <jats:title>Background</jats:title> <jats:p>Traumatic brain injury (TBI) can result in prolonged post-concussive syndrome and chronic hypoxic-ischemic brain injury (HIBI) sequelae remains therapeutically challenging with the persistence of significant neurological and cognitive impairments. While conventional treatments often provide limited relief, emerging research explores alternative therapeutic interventions, including psychedelic compounds combined with therapeutic interventions.</jats:p> </jats:sec> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>This naturalistic case series examines clinical observations following an integrative, participant-directed iboga-containing microdosing protocol paired with Accelerated Experiential Dynamic Psychotherapy (AEDP) in three individuals with persistent neurologic symptoms after traumatic brain injury (TBI) or hypoxic-ischemic brain injury.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Three participants completed a 6 week protocol using Tabernanthe iboga root bark biomass (participant-directed titration 0.1–1.0 g/day, 4 days-on/3 days-off). Quantitative qNMR/HPLC analysis (University of Cape Town) demonstrated approximately 3.845% ibogaine content by mass, yielding estimated ibogaine-equivalent exposure of 3.8–38.5 mg/day. All administration utilized whole root bark biomass only. Weekly AEDP psychotherapy and supportive nutraceuticals were provided concurrently.</jats:p> </jats:sec> <jats:sec> <jats:title>Patient one</jats:title> <jats:p>A 43 year-old man w
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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 articlePasquini L, Girn M, Kettner H, et al., 2026,
Neural correlates of insight on psilocybin: a within-subjects, healthy volunteer study
, JoCN Forum -
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 articleBengoetxea de Tena I, Sallie FN, Rodriguez Abiero A, et al., 2026,
Towards Mechanism-Informed Treatments for Mental Health.
, J Neurochem, Vol: 170Neuropsychiatric disorders represent a significant global health burden. Despite decades of research, current treatments typically provide only symptomatic relief, rather than addressing the underlying mechanisms of these conditions. Historically, research focused on the dopaminergic and serotonergic systems, which are deeply involved in the pathophysiology of many mental health disorders, including depression, schizophrenia, anxiety, autism spectrum disorder (ASD), and different substance use disorders, including alcohol use disorder (AUD). However, therapies targeting these systems have limitations, often only producing partial symptom relief plus compliance-limiting side effects. This highlights the need for improved treatments that may emerge from a broader understanding of the neurobiological bases of these conditions, especially neurochemical systems beyond dopamine and serotonin. Additional monoamines (e.g., histamine, acetylcholine, norepinephrine), neurolipid systems (e.g., endocannabinoids), and diverse signaling molecules such as neuropeptides, trace amines, and cytokines are increasingly recognized as key players in the dysfunction of neural circuits. In this review, which originated from the International Society for Neurochemistry (ISN)/Journal of Neurochemistry 5th Flagship School in October 2024 held in Naxos, Greece, we describe the importance of these neuromodulatory systems in the pathophysiology of select neuropsychiatric disorders, discuss their potential as targets for therapeutic intervention, exploring how they may offer more effective, mechanism-based treatments. We also highlight recent clinical trials, underscoring the progress in advancing towards clinical application, as well as sex-specific neurobiological differences, a historically overlooked, yet fundamental determinant of the pathophysiology of neuropsychiatric disorders. We propose that expanding our focus beyond traditional monoamines offers a promising avenue for the development
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Journal articleSimonsson O, Lyons T, Marks J, et al., 2026,
Effects of psychedelic use on authoritarian attitudes revisited.
, J Psychopharmacol, Vol: 40, Pages: 801-805BACKGROUND: 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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