40 results on '"Nutt D"'
Search Results
2. Psilocybin and Other Classic Psychedelics in Depression
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Nutt, D. J., primary, Peill, J. M., additional, Weiss, B., additional, Godfrey, K., additional, Carhart-Harris, R. L., additional, and Erritzoe, D., additional
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- 2023
- Full Text
- View/download PDF
3. Developing a real-world evidence base for prescribed cannabis in the United Kingdom: preliminary findings from Project Twenty21
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Sakal, C., Lynskey, M., Schlag, A. K., and Nutt, D. J.
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- 2022
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4. Functional aspect of brain PET measures of serotonin examined in depression; relationships with psychometric measures of mood, wellbeing, and connectedness
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Agnorelli, C., primary, Wilgus, K., additional, Weiss, B., additional, Godlewska, B., additional, Cowen, P., additional, Carhart-Harris, R., additional, Fagiolini, A., additional, Nutt, D., additional, Rabiner, E., additional, and Erritzoe, D., additional
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- 2023
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5. Validation of novel fMRI paradigms in gambling disorder
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Zafar, R.R., primary, Wall, M., additional, Nutt, D., additional, and Erritzoe, D., additional
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- 2023
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6. Psilocybin as a treatment for anorexia nervosa: 6-week and 3-month follow-up results
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Douglass, H., primary, Spriggs, M., additional, Godfrey, K., additional, Danby, J., additional, Magalhaes, F., additional, Alderton, K., additional, Macdonald, L., additional, Archer, S., additional, Read, T., additional, Lafrance, A., additional, Nicholls, D., additional, Erritzoe, D., additional, Park, R., additional, Nutt, D., additional, and Carhart-Harris, R., additional
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- 2023
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7. Psychedelic Psychiatry
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Nutt, D., primary
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- 2022
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8. Alterations in white matter microstructure in alcohol and alcohol-polydrug dependence: Associations with lifetime alcohol and nicotine exposure
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Agunbiade, K, Fonville, L, McGonigle, J, Elliott, R, Ersche, KD, Flechais, R, Orban, C, Murphy, A, Smith, DG, Suckling, J, Taylor, EM, Deakin, B, Robbins, TW, Nutt, DJ, Lingford-Hughes, AR, Paterson, LM, Nutt, D, Lingford-Hughes, A, Paterson, L, Taylor, E, Ersche, K, Smith, D, Reed, L, Passetti, F, Faravelli, L, Erritzoe, D, Mick, I, Kalk, N, Waldman, A, Nestor, L, Kuchibatla, S, Boyapati, V, Metastasio, A, Faluyi, Y, Fernandez-Egea, E, Abbott, S, Sahakian, B, Voon, V, Rabiner, I, Orban, C [0000-0001-9133-3561], Paterson, LM [0000-0001-9137-4419], and Apollo - University of Cambridge Repository
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neuroimaging ,polydrug dependence ,DTI ,alcohol dependence ,addiction ,TBSS - Abstract
Funder: GlaxoSmithKline; Id: http://dx.doi.org/10.13039/100004330, Evidence suggests that alcohol dependence (AD) is associated with microstructural deficits in white matter, but the relationship with lifetime alcohol exposure and the impact of polydrug dependence is not well understood. Using diffusion tensor magnetic resonance (MR) imaging, we examined white matter microstructure in relation to alcohol and polydrug dependence using data from the Imperial College Cambridge Manchester (ICCAM) platform study. Tract‐based spatial statistics were used to examine fractional anisotropy (FA) in a cohort of abstinent AD participants, most of whom had a lifetime history of dependence to nicotine. A further subgroup also had a lifetime history of dependence to cocaine and/or opiates. Individuals with AD had lower FA throughout the corpus callosum, and negative associations with alcohol and nicotine exposure were found. A group‐by‐age interaction effect was found showing greater reductions with age in the alcohol‐dependent group within corpus callosum, overlapping with the group difference. We found no evidence of recovery with abstinence. A comparison of alcohol‐only‐ and alcohol‐polydrug‐dependent groups found no differences in FA. Overall, our findings show that AD is associated with lower FA and suggest that these alterations are primarily driven by lifetime alcohol consumption and cigarette smoking, showing no relationship with exposure to other substances such as cocaine, opiates or cannabis. Reductions in FA across the adult lifespan are more pronounced in AD and offer further support for the notion of accelerated ageing in relation to alcohol dependence. These findings highlight there may be lasting structural differences in white matter in alcohol dependence, despite continued abstinence.
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- 2022
9. P.0885 The effect of psilocybin therapy for depression on low-frequency brain activity in response to music
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Wall, M., primary, Lam, C., additional, Ertl, N., additional, Kaelen, M., additional, Roseman, L., additional, Nutt, D., additional, and Carhart-Harris, R., additional
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- 2021
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10. P.0586 Effects of cannabidiol (CBD) alone and combined with Δ9-tetrahydrocannabinol (THC) on functional connectivity of the pain-matrix
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Ertl, N., primary, Wall, M., additional, Pope, R., additional, Freeman, T., additional, Demetriou, L., additional, Yang, Z., additional, Solomons, D., additional, Mokrysz, C., additional, Hindocha, C., additional, Lawn, W., additional, Jones, A., additional, Statton, B., additional, Walker, H., additional, Yamamori, Y., additional, Ying, J. Lok Lim, additional, Bloomfield, M., additional, Freeman, A., additional, Howes, O., additional, Nutt, D., additional, and Curran, H.V., additional
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- 2021
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11. Suicidal Ideation in Medicinal Cannabis Patients: A 12-Month Prospective Study.
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Lynskey, M. T., Thurgur, H., Athanasiou-Fragkouli, A., Schlag, A. K., and Nutt, D. J.
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SUICIDAL ideation , *MEDICAL marijuana , *LONGITUDINAL method , *QUALITY of life , *CHRONIC diseases - Abstract
AbstractObjectiveMethodResultsConclusions\nHIGHLIGHTSTo document the prevalence and correlates of suicidal ideation (SI) among individuals seeking cannabis-based medicinal products (CBMPs); to test whether SI declines or intensifies after three months of CBMP treatment and to document 12-month trajectories of depression in those reporting SI and other patients.Observational data were available for 3781 patients at entry to treatment, 2112 at three months and 777 for 12 months. Self-reported depressed mood and SI were assessed using items from the PHQ-9. Additional data included sociodemographic characteristics and self-reported well-being.25% of the sample reported SI at treatment entry and those with SI had higher levels of depressed mood (mean = 17.4 vs. 11.3;
F (1,3533) = 716.5,p < .001) and disturbed sleep (mean = 13.8 vs. 12.2,F (1,3533) = 125.9,p < .001), poorer general health (mean = 43.6 vs. 52.2,F (1,3533) = 118.3,p < .001) and lower quality of life (mean = 0.44 vs. 0.56 (F (1,3533) = 118.3,p < .001). The prevalence of SI reduced from 23.6% to 17.6% (z = 6.5,p < .001) at 3 months. Twelve-month follow-up indicated a substantial reduction in depressed mood with this reduction being more pronounced in those reporting SI (mean (baseline) = 17.7 vs. mean (12 months) = 10.3) than in other patients (mean (baseline) = 11.1 vs. mean (12 months) = 7.0).SI is common among individuals seeking CBMPs to treat a range of chronic conditions and is associated with higher levels of depressed mood and poorer quality of life. Treatment with CBMPs reduced the prevalence and intensity of suicidal ideation.Suicidal ideation is common among individuals seeking CBMPs for chronic conditionsIt is associated with higher levels of depressed mood and poorer quality of lifeTreatment with CBMPs reduced the prevalence and intensity of suicidal ideationSuicidal ideation is common among individuals seeking CBMPs for chronic conditionsIt is associated with higher levels of depressed mood and poorer quality of lifeTreatment with CBMPs reduced the prevalence and intensity of suicidal ideation [ABSTRACT FROM AUTHOR]- Published
- 2024
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12. A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials
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Luca Sforzini, Courtney Worrell, Melisa Kose, Ian M. Anderson, Bruno Aouizerate, Volker Arolt, Michael Bauer, Bernhard T. Baune, Pierre Blier, Anthony J. Cleare, Philip J. Cowen, Timothy G. Dinan, Andrea Fagiolini, I. Nicol Ferrier, Ulrich Hegerl, Andrew D. Krystal, Marion Leboyer, R. Hamish McAllister-Williams, Roger S. McIntyre, Andreas Meyer-Lindenberg, Andrew H. Miller, Charles B. Nemeroff, Claus Normann, David Nutt, Stefano Pallanti, Luca Pani, Brenda W. J. H. Penninx, Alan F. Schatzberg, Richard C. Shelton, Lakshmi N. Yatham, Allan H. Young, Roland Zahn, Georgios Aislaitner, Florence Butlen-Ducuing, Christine Fletcher, Marion Haberkamp, Thomas Laughren, Fanni-Laura Mäntylä, Koen Schruers, Andrew Thomson, Gara Arteaga-Henríquez, Francesco Benedetti, Lucinda Cash-Gibson, Woo Ri Chae, Heidi De Smedt, Stefan M. Gold, Witte J. G. Hoogendijk, Valeria Jordán Mondragón, Eduard Maron, Jadwiga Martynowicz, Elisa Melloni, Christian Otte, Gabriela Perez-Fuentes, Sara Poletti, Mark E. Schmidt, Edwin van de Ketterij, Katherine Woo, Yanina Flossbach, J. Antoni Ramos-Quiroga, Adam J. Savitz, Carmine M. Pariante, Sforzini, L., Worrell, C., Kose, M., Anderson, I. M., Aouizerate, B., Arolt, V., Bauer, M., Baune, B. T., Blier, P., Cleare, A. J., Cowen, P. J., Dinan, T. G., Fagiolini, A., Ferrier, I. N., Hegerl, U., Krystal, A. D., Leboyer, M., McAllister-Williams, R. H., Mcintyre, R. S., Meyer-Lindenberg, A., Miller, A. H., Nemeroff, C. B., Normann, C., Nutt, D., Pallanti, S., Pani, L., Penninx, B. W. J. H., Schatzberg, A. F., Shelton, R. C., Yatham, L. N., Young, A. H., Zahn, R., Aislaitner, G., Butlen-Ducuing, F., Fletcher, C., Haberkamp, M., Laughren, T., Mantyla, F. -L., Schruers, K., Thomson, A., Arteaga-Henriquez, G., Benedetti, F., Cash-Gibson, L., Chae, W. R., De Smedt, H., Gold, S. M., Hoogendijk, W. J. G., Mondragon, V. J., Maron, E., Martynowicz, J., Melloni, E., Otte, C., Perez-Fuentes, G., Poletti, S., Schmidt, M. E., van de Ketterij, E., Woo, K., Flossbach, Y., Ramos-Quiroga, J. A., Savitz, A. J., Pariante, C. M., Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden = Dresden University of Technology (TU Dresden), The Florey Institute of Neuroscience and Mental Health, University of Melbourne, IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and European Project: (grant No 116060),IMPRiND
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Depression ,Diagnostic markers ,DISORDER ,STIMULATION ,STAR-ASTERISK-D ,SEROTONIN REUPTAKE INHIBITORS ,Major Depressive Disorder ,Clinical Trials and Supportive Activities ,Medical and Health Sciences ,Depressive Disorder, Treatment-Resistant ,Cellular and Molecular Neuroscience ,REPORT QIDS-SR ,SDG 3 - Good Health and Well-being ,Clinical Research ,Humans ,RATING-SCALE ,Molecular Biology ,METAANALYSIS ,Psychiatry ,Depressive Disorder, Major ,Depressive Disorder ,Treatment-Resistant ,Psychology and Cognitive Sciences ,Major ,REMISSION ,Biological Sciences ,Serious Mental Illness ,Brain Disorders ,Psychiatry and Mental health ,QUICK INVENTORY ,Mental Health ,Good Health and Well Being ,SYMPTOMATOLOGY ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] - Abstract
Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.
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- 2022
13. Building Bridges and Connections – The Language used to Connect and Define Communities in the Third Space
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Denney, F, McIntosh, E, and Nutt, D
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- 2022
14. Interrupting the Psychedelic Experience Through Contextual Manipulation to Study Experience Efficacy.
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Roseman L, Erritzoe D, Nutt D, Carhart-Harris R, and Timmermann C
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- Adult, Female, Humans, Male, Hallucinogens therapeutic use, Hallucinogens administration & dosage
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- 2024
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15. Study protocol for "Psilocybin in patients with fibromyalgia: brain biomarkers of action".
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Bornemann J, Close JB, Ahmad K, Barba T, Godfrey K, Macdonald L, Erritzoe D, Nutt D, and Carhart-Harris R
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Background: Chronic pain is a leading cause of disability worldwide. Fibromyalgia is a particularly debilitating form of widespread chronic pain. Fibromyalgia remains poorly understood, and treatment options are limited or moderately effective at best. Here, we present a protocol for a mechanistic study investigating the effects of psychedelic-assisted-therapy in a fibromyalgia population. The principal focus of this trial is the central mechanism(s) of psilocybin-therapy i.e., in the brain and on associated mental schemata, primarily captured by electroencephalography (EEG) recordings of the acute psychedelic state, plus pre and post Magnetic Resonance Imaging (MRI)., Methods: Twenty participants with fibromyalgia will complete 8 study visits over 8 weeks. This will include two dosing sessions where participants will receive psilocybin at least once, with doses varying up to 25mg. Our primary outcomes are 1) Lempel-Ziv complexity (LZc) recorded acutely using EEG, and the 2) the (Brief Experiential Avoidance Questionnaire (BEAQ) measured at baseline and primary endpoint. Secondary outcomes will aim to capture broad aspects of the pain experience and related features through neuroimaging, self-report measures, behavioural paradigms, and qualitative interviews. Pain Symptomatology will be measured using the Brief Pain Inventory Interference Subscale (BPI-IS), physical and mental health-related function will be measured using the 36-Item Short Form Health Survey (SF-36). Further neurobiological investigations will include functional MRI (fMRI) and diffusion tensor imaging (changes from baseline to primary endpoint), and acute changes in pre- vs post-acute spontaneous brain activity - plus event-related potential functional plasticity markers, captured via EEG., Discussion: The results of this study will provide valuable insight into the brain mechanisms involved in the action of psilocybin-therapy for fibromyalgia with potential implications for the therapeutic action of psychedelic-therapy more broadly. It will also deliver essential data to inform the design of a potential subsequent RCT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bornemann, Close, Ahmad, Barba, Godfrey, Macdonald, Erritzoe, Nutt and Carhart-Harris.)
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- 2024
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16. Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression.
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Szigeti B, Weiss B, Rosas FE, Erritzoe D, Nutt D, and Carhart-Harris R
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- Humans, Male, Adult, Female, Double-Blind Method, Middle Aged, Hallucinogens pharmacology, Hallucinogens administration & dosage, Anticipation, Psychological drug effects, Treatment Outcome, Citalopram therapeutic use, Citalopram pharmacology, Citalopram administration & dosage, Psilocybin pharmacology, Psilocybin administration & dosage, Psilocybin therapeutic use, Depressive Disorder, Major drug therapy, Suggestion, Escitalopram pharmacology
- Abstract
Background: To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075)., Methods: We used data ( n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin., Results: Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm., Conclusions: Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.
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- 2024
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17. Is it now time to prepare psychiatry for a psychedelic future?
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Nutt D, Crome I, and Young AH
- Abstract
Australia has just rescheduled two drugs controlled under the United Nations Psychotropic Drug Conventions, psilocybin and MDMA, as treatments for treatment-resistant depression and post-traumatic stress disorder respectively. This feature explores the reasons for these developments, the opportunities and challenges they provide to psychiatry communities and how along with health systems these communities might respond to these developments.
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- 2024
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18. Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity.
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Copa D, Erritzoe D, Giribaldi B, Nutt D, Carhart-Harris R, and Tagliazucchi E
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- Humans, Depression, Escitalopram, Magnetic Resonance Imaging, Psilocybin pharmacology, Psilocybin therapeutic use, Depressive Disorder, Major diagnostic imaging, Depressive Disorder, Major drug therapy
- Abstract
Background: Psilocybin is a serotonergic psychedelic drug under assessment as a potential therapy for treatment-resistant and major depression. Heterogeneous treatment responses raise interest in predicting the outcome from baseline data., Methods: A machine learning pipeline was implemented to investigate baseline resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI) as a predictor of symptom severity in psilocybin monotherapy for treatment-resistant depression (16 patients administered two 5 mg capsules followed by 25 mg, separated by one week). Generalizability was tested in a sample of 22 patients who participated in a psilocybin vs. escitalopram trial for moderate-to-severe major depression (two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo vs. two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram). The analysis was repeated using both samples combined., Results: Functional connectivity of visual, default mode and executive networks predicted early symptom improvement, while the salience network predicted responders up to 24 weeks after treatment (accuracy≈0.9). Generalization performance was borderline significant. Consistent results were obtained from the combined sample analysis. Fronto-occipital and fronto-temporal coupling predicted early and late symptom reduction, respectively., Limitations: The number of participants and differences between the two datasets limit the generalizability of the findings, while the lack of a placebo arm limits their specificity., Conclusions: Baseline neurophysiological measurements can predict the outcome of psilocybin treatment for depression. Future research based on larger datasets should strive to assess the generalizability of these predictions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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19. A perspective on psychedelics as treatments for addictions: Past, Present, and Future.
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Nutt D, Morgan C, and Klaire S
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This Perspectives piece gives a brief overview on the last 70 years of psychedelic research in relation to the treatment of mental illness with a particular focus on addictions. We briefly precis the work in the 19650s/60s that started following the discovery of LSD. Then we overview research developments over the past twenty years driven by emerging neuroscience on these agents, the rise of MDMA use in psychotherapy and the emergence of ketamine as a treatment for mental illnesses. We then briefly outline new research on the brain mechanisms of these therapeutic effects. Finally the current status of research and future challenges in the field are reviewed.
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- 2024
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20. Membrane Permeation of Psychedelic Tryptamines by Dynamic Simulations.
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Palmisano VF, Agnorelli C, Fagiolini A, Erritzoe D, Nutt D, Faraji S, and Nogueira JJ
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Renewed scientific interest in psychedelic compounds represents one of the most promising avenues for addressing the current burden of mental health disorders. Classic psychedelics are a group of compounds that exhibit structural similarities to the naturally occurring neurotransmitter serotonin (5-HT). Acting on the 5-HT type 2A receptors (HT
2A Rs), psychedelics induce enduring neurophysiological changes that parallel their therapeutic psychological and behavioral effects. Recent preclinical evidence suggests that the ability of psychedelics to exert their action is determined by their ability to permeate the neuronal membrane to target a pool of intracellular 5-HT2A Rs. In this computational study, we employ classical molecular dynamics simulations and umbrella sampling techniques to investigate the permeation behavior of 12 selected tryptamines and to characterize the interactions that drive the process. We aim at elucidating the impact of N-alkylation, indole ring substitution and positional modifications, and protonation on their membrane permeability. Dimethylation of the primary amine group and the introduction of a methoxy group at position 5 exhibited an increase in permeability. Moreover, there is a significant influence of positional substitutions on the indole groups, and the protonation of the molecules substantially increases the energy barrier at the center of the bilayer, making the compounds highly impermeable. All the information extracted from the trends predicted by the simulations can be applied in future drug design projects to develop psychedelics with enhanced activity.- Published
- 2024
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21. When the Trial Ends: The Case for Post-Trial Provisions in Clinical Psychedelic Research.
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Jacobs E, Murphy-Beiner A, Rouiller I, Nutt D, and Spriggs MJ
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The ethical value-and to some scholars, necessity-of providing trial patients with post-trial access (PTA) to an investigational drug has been subject to significant attention in the field of research ethics. Although no consensus has emerged, it seems clear that, in some trial contexts, various factors make PTA particularly appropriate. We outline the atypical aspects of psychedelic clinical trials that support the case for introducing the provision of PTA within research in this field, including the broader legal status of psychedelics, the nature of the researcher-therapist/participant relationship, and the extended time-frame of the full therapeutic process. As is increasingly understood, the efficacy of psychedelic-assisted psychotherapy is driven as much by extrapharmacological elements and the cultural therapeutic container as by the drug itself. As such, we also advocate for a refocusing of attention from post-trial access to a broader concept encompassing other elements of post-trial care. We provide an overview of some of the potential post-trial care provisions that may be appropriate in psychedelic clinical trials. Although the World Medical Association's Declaration of Helsinki calls on researchers, sponsors, and governments to make provisions for post-trial access, such provision may feel impracticable or out-of-reach within psychedelic trials that are already constrained by a high resource demand and significant bureaucratic burden. We show how conceiving of post-trial provision as an integral site of the research process, and an appropriate destination for research funding, will serve to develop the infrastructure necessary for the post-legalisation psychedelic medicine ecosystem., Competing Interests: Competing InterestsDN reports advisory roles at COMPASS Pathways, Psyched Wellness, Neural Therapeutics, and Alvarius. EJ is funded by Wellcome Trust grant 221152/Z/20/Z. IR is co-founder and co-director of PsyPAN, and serves as an ACER integration sharing circle facilitator, (© The Author(s) 2023.)
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- 2024
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22. AUD in perspective.
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de Bejczy A, Addolorato G, Aubin HJ, Guiraud J, Korpi ER, John Nutt D, Witkiewitz K, and Söderpalm B
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- Humans, Treatment Outcome, Comorbidity, Alcoholism diagnosis, Alcoholism epidemiology, Alcoholism therapy
- Abstract
Alcohol is a major cause of pre-mature death and individual suffering worldwide, and the importance of diagnosing and treating AUD cannot be overstated. Given the global burden and the high attributable factor of alcohol in a vast number of diseases, the need for additional interventions and the development of new medicines is considered a priority by the World Health Organization (WHO). As of today, AUD is severely under-treated with a treatment gap nearing 90%, strikingly higher than that for other psychiatric disorders. Patients often seek treatment late in the progress of the disease and even among those who seek treatment only a minority receive medication, mirroring the still-prevailing stigma of the disease, and a lack of access to effective treatments, as well as a reluctance to total abstinence. To increase adherence, treatment goals should focus not only on maintaining abstinence, but also on harm reduction and psychosocial functioning. A personalised approach to AUD treatment, with a holistic view, and tailored therapy has the potential to improve AUD treatment outcomes by targeting the heterogeneity in genetics and pathophysiology, as well as reason for, and reaction to drinking. Also, the psychiatric co-morbidity rates are high in AUD and dual diagnosis can worsen symptoms and influence treatment response and should be considered in the treatment strategies., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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23. Bayesian analysis of real-world data as evidence for drug approval: Remembering Sir Michael Rawlins.
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Szigeti B, Phillips LD, and Nutt D
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- Humans, Bayes Theorem, Drug Approval, State Medicine
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- 2023
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24. The New Zealand drug harms ranking study: A multi-criteria decision analysis.
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Crossin R, Cleland L, Wilkins C, Rychert M, Adamson S, Potiki T, Pomerleau AC, MacDonald B, Faletanoai D, Hutton F, Noller G, Lambie I, Sheridan JL, George J, Mercier K, Maynard K, Leonard L, Walsh P, Ponton R, Bagshaw S, Muthukumaraswamy S, McIntosh T, Poot E, Gordon P, Sharry P, Nutt D, and Boden J
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- Adolescent, Humans, New Zealand, Decision Support Techniques, Ethanol, Methamphetamine
- Abstract
Aims: The harms arising from psychoactive drug use are complex, and harm reduction strategies should be informed by a detailed understanding of the extent and nature of that harm. Drug harm is also context specific, and so any comprehensive assessment of drug harm should be relevant to the characteristics of the population in question. This study aimed to evaluate and rank drug harms within Aotearoa New Zealand using a multi-criteria decision analysis (MCDA) framework, and to separately consider harm within the total population, and among youth., Methods: Two facilitated workshops involved the separate ranking of harm for the total population, and then for youth aged 12-17, by two expert panels. In the total population workshop, 23 drugs were scored against 17 harm criteria, and those criteria were then evaluated using a swing weighting process. Scoring and weighting were subsequently updated during the youth-specific workshop. All results were recorded and analysed using specialised MCDA software., Results: When considering overall harm, the MCDA modelling results indicated that alcohol, methamphetamine and synthetic cannabinoids were the most harmful to both the overall population and the youth, followed by tobacco in the total population. Alcohol remained the most harmful drug for the total population when separately considering harm to those who use it, and harm to others., Conclusions: The results provide detailed and context-specific insight into the harm associated with psychoactive drugs use within Aotearoa New Zealand. The findings also demonstrate the value of separately considering harm for different countries, and for different population subgroups.
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- 2023
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25. The difference between 'placebo group' and 'placebo control': a case study in psychedelic microdosing.
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Szigeti B, Nutt D, Carhart-Harris R, and Erritzoe D
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- Humans, Research Design, Hallucinogens pharmacology, Hallucinogens therapeutic use
- Abstract
In medical trials, 'blinding' ensures the equal distribution of expectancy effects between treatment arms in theory; however, blinding often fails in practice. We use computational modelling to show how weak blinding, combined with positive treatment expectancy, can lead to an uneven distribution of expectancy effects. We call this 'activated expectancy bias' (AEB) and show that AEB can inflate estimates of treatment effects and create false positive findings. To counteract AEB, we introduce the Correct Guess Rate Curve (CGRC), a statistical tool that can estimate the outcome of a perfectly blinded trial based on data from an imperfectly blinded trial. To demonstrate the impact of AEB and the utility of the CGRC on empirical data, we re-analyzed the 'self-blinding psychedelic microdose trial' dataset. Results suggest that observed placebo-microdose differences are susceptible to AEB and are at risk of being false positive findings, hence, we argue that microdosing can be understood as active placebo. These results highlight the important difference between 'trials with a placebo-control group', i.e., when a placebo control group is formally present, and 'placebo-controlled trials', where patients are genuinely blind. We also present a new blinding integrity assessment tool that is compatible with CGRC and recommend its adoption., (© 2023. The Author(s).)
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- 2023
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26. Criminalising misuse of nitrous oxide.
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Winstock A and Nutt D
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- Humans, Nitrous Oxide
- Abstract
Competing Interests: Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: AW is the director of Global Drug Survey, an independent research organisation exploring patterns of drug use, publishing academic research, and developing free harm reduction resources. He is the founder of Staying Safer, which produces online courses for university students, clinical groups, and people working with those who use alcohol and other drugs. He has received consultancy payments from several pharmaceutical companies unrelated to nitrous oxide. DN founded and chairs the charity DrugScience, which is funded by individual donations, a grant from Open Society Foundations, and book sales. He sits on the advisory boards of several research and pharmaceutical companies that have no connection to nitrous oxide and has been paid to speak by several pharmaceutical companies that do not produce medical nitrous oxide products. Further details of The BMJ policy on financial interests is here: https://www.bmj.com/sites/default/files/attachments/resources/2016/03/16-current-bmj-education-coi-form.pdf
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- 2023
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27. Default Mode Network Modulation by Psychedelics: A Systematic Review.
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Gattuso JJ, Perkins D, Ruffell S, Lawrence AJ, Hoyer D, Jacobson LH, Timmermann C, Castle D, Rossell SL, Downey LA, Pagni BA, Galvão-Coelho NL, Nutt D, and Sarris J
- Subjects
- Default Mode Network, Psilocybin, Lysergic Acid Diethylamide, Brain diagnostic imaging, Magnetic Resonance Imaging, Hallucinogens pharmacology, Hallucinogens therapeutic use
- Abstract
Psychedelics are a unique class of drug that commonly produce vivid hallucinations as well as profound psychological and mystical experiences. A grouping of interconnected brain regions characterized by increased temporal coherence at rest have been termed the Default Mode Network (DMN). The DMN has been the focus of numerous studies assessing its role in self-referencing, mind wandering, and autobiographical memories. Altered connectivity in the DMN has been associated with a range of neuropsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, attention deficit hyperactive disorder, schizophrenia, and obsessive-compulsive disorder. To date, several studies have investigated how psychedelics modulate this network, but no comprehensive review, to our knowledge, has critically evaluated how major classical psychedelic agents-lysergic acid diethylamide, psilocybin, and ayahuasca-modulate the DMN. Here we present a systematic review of the knowledge base. Across psychedelics there is consistent acute disruption in resting state connectivity within the DMN and increased functional connectivity between canonical resting-state networks. Various models have been proposed to explain the cognitive mechanisms of psychedelics, and in one model DMN modulation is a central axiom. Although the DMN is consistently implicated in psychedelic studies, it is unclear how central the DMN is to the therapeutic potential of classical psychedelic agents. This article aims to provide the field with a comprehensive overview that can propel future research in such a way as to elucidate the neurocognitive mechanisms of psychedelics., (© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.)
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- 2023
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28. Identification and treatment of individuals with attention-deficit/hyperactivity disorder and substance use disorder: An expert consensus statement.
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Young S, Abbasian C, Al-Attar Z, Branney P, Colley B, Cortese S, Cubbin S, Deeley Q, Gudjonsson GH, Hill P, Hollingdale J, Jenden S, Johnson J, Judge D, Lewis A, Mason P, Mukherjee R, Nutt D, Roberts J, Robinson F, Woodhouse E, and Cocallis K
- Abstract
Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with substance use (SU) and/or substance use disorder (SUD). Individuals with concurrent ADHD and SU/SUD can have complex presentations that may complicate diagnosis and treatment. This can be further complicated by the context in which services are delivered. Also, when working with young people and adults with co-existing ADHD and SU/SUD, there is uncertainty among healthcare practitioners on how best to meet their needs. In February 2022, the United Kingdom ADHD Partnership hosted a meeting attended by multidisciplinary experts to address these issues. Following presentations providing attendees with an overview of the literature, group discussions were held synthesizing research evidence and clinical experience. Topics included: (1) A review of substances and reasons for use/misuse; (2) identification, assessment and treatment of illicit SU/SUD in young people and adults with ADHD presenting in community services; and (3) identification, assessment and treatment of ADHD in adults presenting in SU/SUD community and inpatient services. Dis-cussions highlighted inter-service barriers and fragmentation of care. It was concluded that a multimodal and multi-agency approach is needed. The consensus group generated a table of practice recommendations providing guidance on: identification and assessment; pharmacological and psychological treatment; and multi-agency interventions., Competing Interests: Conflict-of-interest statement: Young S, Abbasian C, Cubbin S, Branney P, Colley B, Deeley Q, Hill P, Hollingdale J, Judge D, Lewis A, Mason P, Johnson J and Woodhouse E are affiliated with consultancy firms/private practices. Over the past five years Young S has received honoraria for consultancy and educational talks years from Janssen, Medice and Takeda. She is author of the ADHD Child Evaluation (ACE) and ACE+ for adults; and lead author of R&R2 for ADHD Youths and Adults. Hill P received honoraria for consultancy and educational talks from Takeda and Flynn Pharma. Cortese S declares honoraria and reimbursement for travel and accommodation expenses for lectures from the following non-profit associations: Association for Child and Adolescent Central Health (ACAMH), Canadian ADHD Alliance Resource (CADDRA), British Association of Pharmacology (BAP), and from Healthcare Convention for educational activity on ADHD. Mason P has received honoraria for consultancy and educational talks from Takeda, Flynn Pharma and Lily. Nutt D has received honoraria for educational talks from Takeda and Janssen. Lewis A has received honoraria for consultancy to the Association for Child & Adolescent Mental Health (ACAMH) and Takeda and for educational talks to Forensic Treatment Division, Ministry of Justice, Republic of Korea. Mukherjee R has received honoraria for consultancy and talks related to ADHD from Takeda, Flynn Pharma and Janssen. Johnson J has received honoraria for consultancy and educational talks for Flynn Pharma, Takeda and Janssen. The remaining authors (Gudjonsson GH, Cocallis K, Roberts J, Al-Attar Z, Robinson F) declare that the meeting was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2023
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29. Canalization and plasticity in psychopathology.
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Carhart-Harris RL, Chandaria S, Erritzoe DE, Gazzaley A, Girn M, Kettner H, Mediano PAM, Nutt DJ, Rosas FE, Roseman L, Timmermann C, Weiss B, Zeifman RJ, and Friston KJ
- Subjects
- United States, Humans, Phenotype, Learning, Depressive Disorder, Major
- Abstract
This theoretical article revives a classical bridging construct, canalization, to describe a new model of a general factor of psychopathology. To achieve this, we have distinguished between two types of plasticity, an early one that we call 'TEMP' for 'Temperature or Entropy Mediated Plasticity', and another, we call 'canalization', which is close to Hebbian plasticity. These two forms of plasticity can be most easily distinguished by their relationship to 'precision' or inverse variance; TEMP relates to increased model variance or decreased precision, whereas the opposite is true for canalization. TEMP also subsumes increased learning rate, (Ising) temperature and entropy. Dictionary definitions of 'plasticity' describe it as the property of being easily shaped or molded; TEMP is the better match for this. Importantly, we propose that 'pathological' phenotypes develop via mechanisms of canalization or increased model precision, as a defensive response to adversity and associated distress or dysphoria. Our model states that canalization entrenches in psychopathology, narrowing the phenotypic state-space as the agent develops expertise in their pathology. We suggest that TEMP - combined with gently guiding psychological support - can counter canalization. We address questions of whether and when canalization is adaptive versus maladaptive, furnish our model with references to basic and human neuroscience, and offer concrete experiments and measures to test its main hypotheses and implications. This article is part of the Special Issue on "National Institutes of Health Psilocybin Research Speaker Series"., Competing Interests: Declaration of competing interest RCH, DE, AG, DJN report being a scientific advisor to a number of new companies and not-for-profits that are seeking to develop psychedelic therapy and bring it to market. RCH is grateful to Meg Spriggs for comments on an earlier draft of this manuscript, Courtney Gallen for guidance on referencing brain network modularity findings, Rayyan Zafar for references on dopamine, stimulants and Hebbian mechanisms, Lindsay Cameron for references on environmental enrichment and neuroplasticity, and Max Wolff for the connection to the ideas of Klaus Grawe., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2023
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30. Psychedelics therapeutics: What we know, what we think, and what we need to research.
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Nutt D, Spriggs M, and Erritzoe D
- Subjects
- Hallucinogens pharmacology, Hallucinogens therapeutic use, Psychiatry
- Abstract
Psychedelic therapy is perhaps the most exciting new development in psychiatry. Not only does it offer a radical new approach to treatment where mainstream approaches have proven ineffective, but the growing evidence for transdiagnostic efficacy is eliciting a re-think of current diagnostic and symptom-specific approaches to psychiatry. This excitement has led to a massive investment in this field with many tens of new pharmaceutical companies being set up to research the effects of known psychedelics and develop new patentable molecules. Whilst this enthusiasm is to be welcomed, it is important that new research is properly grounded in established facts and reflects current knowledge. In this commentary we lay out the knowledge framework that should be taken into account by all innovative researchers in this field., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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31. Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression.
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Shukuroglou M, Roseman L, Wall M, Nutt D, Kaelen M, and Carhart-Harris R
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- Humans, Psilocybin pharmacology, Psilocybin therapeutic use, Anhedonia physiology, Depression drug therapy, Emotions, Magnetic Resonance Imaging, Music psychology, Hallucinogens pharmacology, Hallucinogens therapeutic use
- Abstract
Background: Music listening is a staple and valued component of psychedelic therapy, and previous work has shown that psychedelics can acutely enhance music-evoked emotion., Aims: The present study sought to examine subjective responses to music before and after psilocybin therapy for treatment-resistant depression, while functional magnetic resonance imaging (fMRI) data was acquired., Methods: Nineteen patients with treatment-resistant depression received a low oral dose (10 mg) of psilocybin, and a high dose (25 mg) 1 week later. fMRI was performed 1 week prior to the first dosing session and 1 day after the second. Two scans were conducted on each day: one with music and one without. Visual analogue scale ratings of music-evoked 'pleasure' plus ratings of other evoked emotions (21-item Geneva Emotional Music Scale) were completed after each scan. Given its role in musical reward, the nucleus accumbens (NAc) was chosen as region of interest for functional connectivity (FC) analyses. Effects of drug (vs placebo) and music (vs no music) on subjective and FC outcomes were assessed. Anhedonia symptoms were assessed pre- and post-treatment (Snaith-Hamilton Pleasure Scale)., Results: Results revealed a significant increase in music-evoked emotion following treatment with psilocybin that correlated with post-treatment reductions in anhedonia. A post-treatment reduction in NAc FC with areas resembling the default mode network was observed during music listening (vs no music)., Conclusion: These results are consistent with current thinking on the role of psychedelics in enhancing music-evoked pleasure and provide some new insight into correlative brain mechanisms.
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- 2023
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32. The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world.
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Watts R, Kettner H, Geerts D, Gandy S, Kartner L, Mertens L, Timmermann C, Nour MM, Kaelen M, Nutt D, Carhart-Harris R, and Roseman L
- Subjects
- Humans, Psilocybin therapeutic use, Emotions, Surveys and Questionnaires, Hallucinogens pharmacology, Hallucinogens therapeutic use, Depressive Disorder, Major drug therapy
- Abstract
Rationale: A general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of 'connectedness' as 'a state of feeling connected to self, others and the wider world'. Existing tools for measuring connectedness have focused on particular aspects of connectedness, such as 'social connectedness' or 'nature connectedness', which we hypothesise to be different expressions of a common factor of connectedness. Here, we sought to develop a new scale to measure connectedness as a construct with these multiple domains. We hypothesised that (1) our scale would measure three separable subscale factors pertaining to a felt connection to 'self', 'others' and 'world' and (2) improvements in total and subscale WCS scores would correlate with improved mental health outcomes post psychedelic use., Objectives: To validate and test the 'Watts Connectedness Scale' (WCS)., Methods: Psychometric validation of the WCS was carried out using data from three independent studies. Firstly, we pooled data from two prospective observational online survey studies. The WCS was completed before and after a planned psychedelic experience. The total sample of completers from the online surveys was N = 1226. Exploratory and confirmatory factor analysis were performed, and construct and criterion validity were tested. A third dataset was derived from a double-blind randomised controlled trial (RCT) comparing psilocybin-assisted therapy (n = 27) with 6 weeks of daily escitalopram (n = 25) for major depressive disorder (MDD), where the WCS was completed at baseline and at a 6-week primary endpoint., Results: As hypothesised, factor analysis of all WCS items revealed three main factors with good internal consistency. WCS showed good construct validity. Significant post-psychedelic increases were observed for total connectedness scores (η2 = 0.339, p < 0.0001), as well as on each of its subscales (p < 0.0001). Acute measures of 'mystical experience', 'emotional breakthrough', and 'communitas' correlated positively with post-psychedelic changes in connectedness (r = 0.42, r = 0.38, r = 0.42, respectively, p < 0.0001). In the RCT, psilocybin therapy was associated with greater increases in WCS scores compared with the escitalopram arm (η
p 2 = 0.133, p = 0.009)., Conclusions: The WCS is a new 3-dimensional index of felt connectedness that may sensitively measure therapeutically relevant psychological changes post-psychedelic use. We believe that the operational definition of connectedness captured by the WCS may have broad relevance in mental health research., (© 2022. The Author(s).)- Published
- 2022
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33. Effects of classic psychedelic drugs on turbulent signatures in brain dynamics.
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Cruzat J, Perl YS, Escrichs A, Vohryzek J, Timmermann C, Roseman L, Luppi AI, Ibañez A, Nutt D, Carhart-Harris R, Tagliazucchi E, Deco G, and Kringelbach ML
- Abstract
Psychedelic drugs show promise as safe and effective treatments for neuropsychiatric disorders, yet their mechanisms of action are not fully understood. A fundamental hypothesis is that psychedelics work by dose-dependently changing the functional hierarchy of brain dynamics, but it is unclear whether different psychedelics act similarly. Here, we investigated the changes in the brain's functional hierarchy associated with two different psychedelics (LSD and psilocybin). Using a novel turbulence framework, we were able to determine the vorticity, that is, the local level of synchronization, that allowed us to extend the standard global time-based measure of metastability to become a local-based measure of both space and time. This framework produced detailed signatures of turbulence-based hierarchical change for each psychedelic drug, revealing consistent and discriminate effects on a higher level network, that is, the default mode network. Overall, our findings directly support a prior hypothesis that psychedelics modulate (i.e., "compress") the functional hierarchy and provide a quantification of these changes for two different psychedelics. Implications for therapeutic applications of psychedelics are discussed., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2022 Massachusetts Institute of Technology.)
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- 2022
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34. Acceptability of donor funding for clinical trials in the UK: a qualitative empirical ethics study using focus groups to elicit the views of research patient public involvement group members, research ethics committee chairs and clinical researchers.
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Shearman K, Masters A, Nutt D, Bowman S, and Draper H
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- Clinical Trials as Topic, Focus Groups, Humans, Research Personnel, United Kingdom, Ethical Review, Ethics Committees, Research
- Abstract
Objectives: The Plutocratic Proposal is a novel method of funding early phase clinical trials where a single donor funds the entire trial and in so doing secures a place on it. The aim of this study was to identify and explore concerns that may be raised by UK research ethics committees (RECs) when reviewing clinical trials funded in this way., Design: Empirical ethics combining ethical analysis and qualitative data from three focus groups held online using Frith's symbiotic approach. Data were analysed using inductive thematic approach informed by the study aims and ethical analysis., Participants: 22 participants were recruited: 8 research patient public involvement group members, 7 REC chairs and 7 clinical researchers. All were based in the UK., Results: With one exception, participants thought the Plutocratic Proposal may be 'all things considered' acceptable, providing their concerns were met, primary of which was upholding scientific integrity. Other concerns discussed related to the acceptability of the donor securing a place on the trial including: whether this was an unfair distribution of benefits, disclosing the identity of the donor as the funder, protecting the donor from exploitation and funding a single study with multiple donors on the same terms. Some misgivings fell outside the usual REC purview: detrimental impact of donors of bad character, establishing the trustworthiness of the matching agency and its processes and optimising research funding and resources. Despite their concerns, participants recognised that because the donor funds the whole trial, others would also potentially benefit from participating., Conclusions: We identified concerns about the Plutocratic Proposal. UK RECs may be open to approving studies if these can be addressed. Existing governance processes will do some of this work, but additional REC guidance, particularly in relation to donors securing a place on the trial, may be necessary to help RECs navigate ethical concerns consistently., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare funding for this project from UK Spine. HD is employed by the University of Warwick. KS was a doctoral researcher in receipt of a research stipend from the University of Warwick until September 2021 when she took up a post with the HRA but does not now represent their views. KS, DN, AM and HD received funding from UK Spine for time contributed to this study. In the past three years, HD has received unrelated research funding from the Arts and Humanities Research Council, National Institute for Health Research and CIFAR, and is an unpaid member of DMS Ethics Committee, the Ethics Advisory Group of Birmingham Women’s and Children’s Hospitals Foundation Trust and NHS BT Deceased Donor Family Tissue Advisory Group. DN is a self-employed communications specialist currently working on an unrelated, fixed term contract as Head of Communications for the University of Warwick. In the past 3 years, he has had contracts with Sutton Council, Newham Council, the Scouting Association, the London Assembly and Plymouth Council. He is retained by Sutton Council to develop the London Cancer Hub. AM is a freelance writer, illustrator and teacher. Together, AM and DN established and raised funds for iCancer, a not-for-profit patients support group. SB’s salary is part-funded by the Birmingham Biomedical Research Centre and has provided paid consultancy in the field of Sjogren’s clinical trial design in the past three years to Abbvie, Astra Zeneca, Galapagos and Novartis., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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35. Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey.
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Kuc J, Kettner H, Rosas F, Erritzoe D, Haijen E, Kaelen M, Nutt D, and Carhart-Harris RL
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- Analgesics pharmacology, Cannabinoid Receptor Agonists pharmacology, Emotions, Humans, Prospective Studies, Surveys and Questionnaires, Cannabis, Hallucinogens pharmacology
- Abstract
Rationale: Classic psychedelics are currently being studied as novel treatments for a range of psychiatric disorders. However, research on how psychedelics interact with other psychoactive substances remains scarce., Objectives: The current study aimed to explore the subjective effects of psychedelics when used alongside cannabis., Methods: Participants (n = 321) completed a set of online surveys at 2 time points: 7 days before, and 1 day after a planned experience with a serotonergic psychedelic. The collected data included demographics, environmental factors (so-called setting) and five validated questionnaires: Mystical Experience Questionnaire (MEQ), visual subscales of Altered States of Consciousness Questionnaire (ASC-Vis), Challenging Experience Questionnaire (CEQ), Ego Dissolution Inventory (EDI) and Emotional Breakthrough Inventory (EBI). Participants were grouped according to whether they had reported using no cannabis (n = 195) or low (n = 53), medium (n = 45) or high (n = 28) dose, directly concomitant with the psychedelic. Multivariate analysis of covariance (MANCOVA) and contrasts was used to analyse differences in subjective effects between groups while controlling for potential confounding contextual 'setting' variables., Results: The simultaneous use of cannabis together with classic serotonergic psychedelics was associated with more intense psychedelic experience across a range of measures: a linear relationship was found between dose and MEQ, ASC-Vis and EDI scores, while a quadratic relationship was found for CEQ scores. No relationship was found between the dose of cannabis and the EBI., Conclusions: Results imply a possible interaction between the cannabis and psychedelic on acute subjective experiences; however, design limitations hamper our ability to draw firm inferences on directions of causality and the clinical implications of any such interactions., (© 2021. The Author(s).)
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- 2022
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36. Increased global integration in the brain after psilocybin therapy for depression.
- Author
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Daws RE, Timmermann C, Giribaldi B, Sexton JD, Wall MB, Erritzoe D, Roseman L, Nutt D, and Carhart-Harris R
- Subjects
- Antidepressive Agents pharmacology, Antidepressive Agents therapeutic use, Brain diagnostic imaging, Depression diagnostic imaging, Depression drug therapy, Double-Blind Method, Escitalopram, Humans, Psilocybin pharmacology, Psilocybin therapeutic use, Depressive Disorder, Major diagnostic imaging, Depressive Disorder, Major drug therapy, Hallucinogens therapeutic use
- Abstract
Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the subacute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10 mg and 25 mg, 7 d apart) in patients with treatment-resistant depression. Functional magnetic resonance imaging (fMRI) was recorded at baseline and 1 d after the 25-mg dose. Beck's depression inventory was the primary outcome measure ( MR/J00460X/1 ). The second trial was a double-blind phase II randomized controlled trial comparing psilocybin therapy with escitalopram. Patients with major depressive disorder received either 2 × 25 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo ('psilocybin arm') or 2 × 1 mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram (10-20 mg) ('escitalopram arm'). fMRI was recorded at baseline and 3 weeks after the second psilocybin dose ( NCT03429075 ). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in fMRI brain network modularity, implying that psilocybin's antidepressant action may depend on a global increase in brain network integration. Network cartography analyses indicated that 5-HT2A receptor-rich higher-order functional networks became more functionally interconnected and flexible after psilocybin treatment. The antidepressant response to escitalopram was milder and no changes in brain network organization were observed. Consistent efficacy-related brain changes, correlating with robust antidepressant effects across two studies, suggest an antidepressant mechanism for psilocybin therapy: global increases in brain network integration., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2022
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37. Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression.
- Author
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Murphy R, Kettner H, Zeifman R, Giribaldi B, Kartner L, Martell J, Read T, Murphy-Beiner A, Baker-Jones M, Nutt D, Erritzoe D, Watts R, and Carhart-Harris R
- Abstract
Background: Across psychotherapeutic frameworks, the strength of the therapeutic alliance has been found to correlate with treatment outcomes; however, its role has never been formally assessed in a trial of psychedelic-assisted therapy. We aimed to investigate the relationships between therapeutic alliance and rapport, the quality of the acute psychedelic experience and treatment outcomes. Methods: This 2-arm double-blind randomized controlled trial compared escitalopram with psychedelic-assisted therapy for moderate-severe depressive disorder ( N = 59). This analysis focused on the psilocybin condition ( n = 30), who received two oral doses of 25 mg psilocybin, 3-weeks apart, with psychological preparation, in-session support, and integration therapy. A new psychedelic therapy model, called "Accept-Connect-Embody" (ACE), was developed in this trial. The primary outcome was depression severity 6 weeks post treatment (Quick Inventory of Depressive Symptomatology, QIDS-SR-16). Path analyses tested the hypothesis that therapeutic alliance (Scale To Assess the Therapeutic Relationship Patient Version, STAR-P) would predict depression outcomes via its influence on the acute psychedelic experience, specifically emotional-breakthrough (EBI) and mystical-type experiences (MEQ). The same analysis was performed on the escitalopram arm to test specificity. Results: The strength of therapeutic alliance predicted pre-session rapport, greater emotional-breakthrough and mystical-type experience (maximum EBI and MEQ scores across the two psilocybin sessions) and final QIDS scores ( β = -0.22, R
2 = 0.42 for EBIMax ; β = -0.19, R2 = 0.32 for MEQMax ). Exploratory path models revealed that final depression outcomes were more strongly affected by emotional breakthrough during the first, and mystical experience during the second session. Emotional breakthrough, but not mystical experience, during the first session had a positive effect on therapeutic alliance ahead of the second session ( β = 0.79, p < 0.0001). Therapeutic alliance ahead of the second session had a direct impact on final depression scores, not mediated by the acute experience, with a weaker alliance ahead of the second psilocybin session predicting higher absolute depression scores at endpoint ( β = -0.49, p < 0.001) Discussion: Future research could consider therapist training and characteristics; specific participant factors, e.g., attachment style or interpersonal trauma, which may underlie the quality of the therapeutic relationship, the psychedelic experience and clinical outcomes; and consider how therapeutic approaches might adapt in cases of weaker therapeutic alliance. Clinical Trial Registration: This trial is registered at http://clinicaltrials.gov, identifier (NCT03429075)., Competing Interests: Carhart-Harris sits on the scientific advisory boards of: Entheon Biomedical, Mydecine, Synthesis Institute, Tryp Therapeutics, Usona Institute, Osmind, Beckley Pscyhtech, Journey Collab and Maya Health. Giribaldi, receiving consulting fees from SmallPharma; Watts, receiving advisory board fees from Usona Institute and being employed by Synthesis Institute; Baker-Jones, receiving fees from Synthesis Institute and employed by Small Pharma; Erritzoe, receiving consulting fees from Field Trip and Mydecine; and Nutt, receiving consulting fees from Awakn, H. Lundbeck, and Psyched Wellness, advisory board fees from COMPASS Pathways, and lecture fees from Takeda Medical Research Foundation and owning stock in Alcarelle. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Murphy, Kettner, Zeifman, Giribaldi, Kartner, Martell, Read, Murphy-Beiner, Baker-Jones, Nutt, Erritzoe, Watts and Carhart-Harris.)- Published
- 2022
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38. A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials.
- Author
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Sforzini L, Worrell C, Kose M, Anderson IM, Aouizerate B, Arolt V, Bauer M, Baune BT, Blier P, Cleare AJ, Cowen PJ, Dinan TG, Fagiolini A, Ferrier IN, Hegerl U, Krystal AD, Leboyer M, McAllister-Williams RH, McIntyre RS, Meyer-Lindenberg A, Miller AH, Nemeroff CB, Normann C, Nutt D, Pallanti S, Pani L, Penninx BWJH, Schatzberg AF, Shelton RC, Yatham LN, Young AH, Zahn R, Aislaitner G, Butlen-Ducuing F, Fletcher C, Haberkamp M, Laughren T, Mäntylä FL, Schruers K, Thomson A, Arteaga-Henríquez G, Benedetti F, Cash-Gibson L, Chae WR, De Smedt H, Gold SM, Hoogendijk WJG, Mondragón VJ, Maron E, Martynowicz J, Melloni E, Otte C, Perez-Fuentes G, Poletti S, Schmidt ME, van de Ketterij E, Woo K, Flossbach Y, Ramos-Quiroga JA, Savitz AJ, and Pariante CM
- Subjects
- Depression, Humans, Depressive Disorder, Major drug therapy, Depressive Disorder, Treatment-Resistant drug therapy
- Abstract
Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD., (© 2021. The Author(s).)
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- 2022
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39. UK drugs strategy promises to be tough on criminals, but evidence shows this doesn't work.
- Author
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Nutt D
- Subjects
- Humans, United Kingdom, Criminals, Illicit Drugs legislation & jurisprudence
- Abstract
Competing Interests: Competing interests: DN is founding chair of the charity Drug Science. He also advises Awkan and COMPASSPathways, two companies with an interest in developing psychedelic medicines for the treatment of addiction.
- Published
- 2021
- Full Text
- View/download PDF
40. Alcohol and the Brain.
- Author
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Nutt D, Hayes A, Fonville L, Zafar R, Palmer EOC, Paterson L, and Lingford-Hughes A
- Subjects
- Alcoholism diagnostic imaging, Alcoholism physiopathology, Behavior, Addictive, Brain diagnostic imaging, Craving physiology, Fetal Alcohol Spectrum Disorders, Functional Neuroimaging, Humans, Alcohol Drinking adverse effects, Brain drug effects
- Abstract
Alcohol works on the brain to produce its desired effects, e.g., sociability and intoxication, and hence the brain is an important organ for exploring subsequent harms. These come in many different forms such as the consequences of damage during intoxication, e.g., from falls and fights, damage from withdrawal, damage from the toxicity of alcohol and its metabolites and altered brain structure and function with implications for behavioral processes such as craving and addiction. On top of that are peripheral factors that compound brain damage such as poor diet, vitamin deficiencies leading to Wernicke-Korsakoff syndrome. Prenatal alcohol exposure can also have a profound impact on brain development and lead to irremediable changes of fetal alcohol syndrome. This chapter briefly reviews aspects of these with a particular focus on recent brain imaging results. Cardiovascular effects of alcohol that lead to brain pathology are not covered as they are dealt with elsewhere in the volume.
- Published
- 2021
- Full Text
- View/download PDF
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