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Journal articleSiegel JS, Liston C, Nicol GE, et al., 2026,
The science of psychedelic medicine.
, Nat MedClassic psychedelics typically act at the serotonin 5-HT2A receptor to profoundly alter brain function and consciousness. Research on these compounds has accelerated. Major strides have been made in understanding their unique mechanisms of action and clinical potential. This Review outlines the state of psychedelic science, spanning cellular mechanisms, systems neuroscience and clinical investigation. We show that preclinical and human research findings converge on two complementary processes: acute neural desynchronization, which destabilizes entrenched network patterns, and subacute neuroplasticity, which opens a window for psychological and behavioral change. We review evidence of therapeutic response across neuropsychiatric indications and consider how this integrates with mechanistic findings. We also explore challenges and opportunities, including discrepancies between preclinical evidence that non-hallucinogenic psychedelic analogs engage putative therapeutic mechanisms, and clinical evidence linking the subjective experience to therapeutic response; the risks inherent to enhanced neuroplasticity; and questions surrounding trial design, scalability and regulatory approval. The growth of psychedelic science and medicine may compel a fundamental rethinking of the relationship between subjective experience and biological change in psychiatry.
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Journal articleKurtin DL, Herlinger K, Hayes A, et al., 2026,
Task-related differences in network connectivity and dynamics in people with severe opioid use disorder compared with healthy controls
, Translational Psychiatry, ISSN: 2158-3188<jats:sec> <jats:title>Abstract</jats:title> <jats:p> One approach to addressing the immense unmet need for treatments of severe opioid use disorder (sOUD) is to understand more about associated changes in the brain’s reward circuitry. It has been shown that during reward anticipation in the Monetary Incentive Delay (MID) task, people with severe substance use disorder (SUD) show blunted responses in reward neural circuitry compared with healthy controls (HC). Conversely, drug-related cues result in heightened responses in the same neural reward circuitry in those with SUD compared with HC. However, it is unclear how such dysfunctional reward processing is related to neural correlates of other processes commonly dysregulated in addiction, such as attention and cognition. The aim of this work was to evaluate whether people with sOUD show different relationships between reward networks to networks that regulate cognition, attention, sensory processes, and more. Then, we evaluated whether there is a spatial relationship between differences in brain function and atlases of μ-opioid receptor (MOR) and dopamine D <jats:sub>2</jats:sub> receptor (DRD2) availability. We collected fMRI data while people with sOUD receiving methadone (MD; n = 25) and HC (n = 22) completed the MID and cue reactivity tasks. We evaluated differences in functional connectivity (FC) and measures of brain state dynamics. Partial least squared (PLS) analysis computed the spatial relationship between FC metrics to MOR and D2DR availability. We found that MD participants generally exhibited weaker miFC compared to HC in both tasks except when comparing the difference in miFC during anticipation of monetary reward or drug related stimuli vs neutral stimuli. Contrasts between rewarding or drug-related to neutral stimuli showed MD pa
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Journal articleCrépault J-F, Russell C, Asbridge M, et al., 2026,
Drug harms in Canada: A multi-criteria decision analysis.
, J PsychopharmacolBACKGROUND: Multi-criteria decision analysis (MCDA) has been used to quantify drug harms in the United Kingdom, the European Union, Australia, and New Zealand. This paper presents the result of an MCDA conducted in Canada, with the aim of informing Canadian drug policy and contributing to public understanding of drugs' relative harms. METHODS: A panel composed of 20 experts from six provinces determined 16 drugs to evaluate on 16 dimensions of harm (ten representing harm to people who use the drug; six representing harm to others). At a two-day decision conference, the panel scored each drug on a scale of 0-100 for each harm criterion, then weighted the relative importance of each criterion. RESULTS: This analysis of drug harms in Canada found that alcohol causes the most harm overall, with a cumulative weighted score of 79. It was followed by tobacco (45), nonprescription opioids (33), cocaine (19), methamphetamine (19), and cannabis (15). The finding that alcohol causes the most harm is consistent with the results of previous MCDA drug harm studies. CONCLUSION: These harm scores express population-level harm rather than individual-level "harmfulness." They reflect not only a drug's pharmacological risk profile but also the current policy context in Canada. The high score for alcohol underscores a failure to adopt policies to address alcohol-related harms, despite the known health harms and the existence of proven policy measures. More broadly, when developing drug policies, governments should consider the harm-both individual and societal-caused by drugs and by the laws and regulations that govern them.
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Journal articleGoodwin GM, Aaronson ST, Alvarez O, et al., 2026,
Corrigendum to "The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression" [Journal of Affective Disorders, Volume 372 (2025), Pages 523-532].
, J Affect Disord, Vol: 393 -
Journal articleIrrmischer M, Aqil M, Luan L, et al., 2026,
DMT-Induced Shifts in Criticality Correlate with Self-Dissolution.
, J Neurosci, Vol: 46Psychedelics profoundly alter subjective experience and brain dynamics. Brain oscillations express signatures of near-critical dynamics, relevant for healthy function. Alterations in the proximity to criticality have been suggested to underlie the experiential and neurological effects of psychedelics. Here, we investigate the effects of a psychedelic substance (DMT) on the criticality of brain oscillations, and in relation to subjective experience, in humans of either sex. We find that DMT shifts the dynamics of brain oscillations away from criticality in alpha and adjacent frequency bands. In this context, entropy is increased while complexity is reduced. We find that the criticality-shifts observed in alpha and theta bands correlate with the intensity ratings of self-dissolution, a hallmark of psychedelic experience. Finally, using a recently developed metric, the functional excitatory-inhibitory ratio, we find that the DMT-induced criticality-shift in brain oscillations is toward subcritical regimes. These findings have major implications for the neuronal understanding of the self and psychedelics, as well as for the neurological basis of altered states of consciousness.
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Journal articleWall MB, Demetriou L, Giribaldi B, et al., 2026,
Thresholding and Perfusion Considerations in Interpreting Reduced Brain Responsiveness With Escitalopram: Response to Knudsen et al.
, Am J Psychiatry, Vol: 183, Pages: 80-81 -
Journal articleZafar R, 2025,
High hopes? Precision psychedelic addiction medicine
, Frontiers in Psychiatry, ISSN: 1664-0640Despite decades of neuroscience research and significant investment in addiction neuroimaging, clinical outcomes for individuals with substance use and behavioural addictions remain poor. Only 1.8% of people with substance use disorders receive effective treatment, highlighting a major disconnect between mechanistic understanding and clinical utility. This paper calls for a reorientation of addiction neuroscience, from a predominantly diagnostic focus toward a theragnostic framework, in which biomarkers are used to stratify patients, guide treatment decisions, and predict outcomes. We argue that the integration of translational neuroimaging biomarkers, particularly fMRI, EEG, and PET, within psychedelic addiction research offers a unique and timely opportunity to catalyse this shift. Psychedelic compounds such as psilocybin represent a new class of therapeutics capable of engaging neuroplasticity, reward and emotional processing, and cognitive control networks central to addiction pathophysiology. We review how acute and pre– post neuroimaging paradigms can index pharmacodynamic effects and longer-term treatment response and propose a roadmap for embedding biomarkers in early and late phase clinical trials. Drawing on ongoing studies at the Centre for Psychedelic Research at Imperial College London, we outline how multimodal biomarkers are being co-developed alongside clinical trials in gambling and opioid use disorders to identify biotype-specific responses and build a deeply phenotyped treatment population. We argue that these biomarkers, if validated, could serve as regulatory-grade tools for drug theragnostic co-development, mirroring successful models in oncology and 2 neurology. Importantly, we emphasise that realising this vision will require robust multi-stakeholder collaboration, including academia, industry, regulatory agencies, funders, healthcare systems, and patient groups alongside dedicated investment to build a scalable theragnostic infrastruct
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Journal articleNutt DJ, 2025,
Farewell to Jim Watson (and Francis Crick). A reflection on their contributions to psychiatry and brain science.
, J Psychopharmacol -
Journal articleGordon AR, Carrithers BM, Pagni BA, et al., 2025,
The Effect of Psychedelics on Individuals with a Personality Disorder: Results from Two Prospective Cohort Studies
, PSYCHEDELIC MEDICINE, ISSN: 2831-4425 -
Journal articleMehmood MK, Bremler R, Spriggs MJ, et al., 2025,
Ceremonial Psychedelic Experiences and Changes in Mental Health Outcomes in Those with Adverse Childhood Experiences
, PSYCHEDELIC MEDICINE, ISSN: 2831-4425
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