Imperial College London

Professor David Nutt DM, FRCP, FRCPsych, FSB, FMedSci

Faculty of MedicineDepartment of Brain Sciences

The Edmond J Safra Chair in Neuropsychopharmacology
 
 
 
//

Contact

 

d.nutt

 
 
//

Location

 

Burlington Danes BuildingBurlington DanesHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

1373 results found

Nutt DJ, 2023, Pharmacological Dissection of Antipsychotics., Biol Psychiatry, Vol: 94, Pages: 524-525

Journal article

Simonsson O, Carlbring P, Carhart-Harris R, Davis AK, Nutt DJ, Griffiths RR, Erritzoe D, Goldberg SBet al., 2023, Assessing the risk of symptom worsening in psilocybin-assisted therapy for depression: A systematic review and individual participant data meta-analysis., Psychiatry Res, Vol: 327

We conducted a meta-analysis using individual participant data from three, two-dose psilocybin trials for depression (N = 102) with the aim of assessing the risk of symptom worsening. Clinically significant symptom worsening occurred for a minority of participants in the psilocybin and escitalopram conditions (∼10%) and for a majority of participants in the waitlist condition (63.6%). Using data from the two trials with control arms, the psilocybin arm showed a lower likelihood of symptom worsening versus waitlist, and no difference in the likelihood of symptom worsening versus escitalopram. The limitation of a relatively small sample size should be addressed in future studies.

Journal article

Szigeti B, Phillips LD, Nutt D, 2023, Bayesian analysis of real-world data as evidence for drug approval: Remembering Sir Michael Rawlins., Br J Clin Pharmacol, Vol: 89, Pages: 2646-2648

Journal article

Thurgur H, Schlag AK, Iveson E, Hosseini A, Lynskey M, Nutt DJet al., 2023, Cannabis-based medicinal products (CBMPs) for the treatment of Long COVID symptoms: current and potential applications, Exploration of Medicine, Pages: 487-503

<jats:p>Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can result in a range of persistent symptoms impacting everyday functioning for a considerable proportion of patients, a condition termed Long coronavirus disease (COVID) or post COVID-19 syndrome. The severity and set of symptoms vary between patients, and include fatigue, cognitive dysfunction, sleep disturbances, palpitations, tachycardia, pain, depression, and anxiety. The high prevalence of Long COVID combined with the lack of treatment approaches has resulted in considerable unmet clinical needs. There is a growing body of evidence that cannabis-based medicinal products (CBMPs) can be used to treat symptoms including pain, anxiety, depression, fatigue, sleep, headaches, and cognitive dysfunction, which are commonly reported in Long COVID. This article provides an overview of the pathophysiology of Long COVID and discusses preliminary pre-clinical, clinical trials, and real-world evidence (RWE) for CBMPs in the context of Long COVID. This review summarises current clinical trials and studies exploring CBMPs in Long COVID. The current evidence provides a rationale to further explore CBMPs as a treatment for Long COVID symptoms. In addition to further randomised controlled trials (RCTs), the increasing availability of CBMPs globally, coupled with the continued prevalence of Long COVID in the population, also highlights the value of real-world data in the research of CBMPs in Long COVID. Critically, there is an evident need for multidisciplinary approaches of CBMPs and Long COVID in real-world clinical practice settings.</jats:p>

Journal article

Jauhar S, Arnone D, Baldwin DS, Bloomfield M, Browning M, Cleare AJ, Corlett P, Deakin JFW, Erritzoe D, Fu C, Fusar-Poli P, Goodwin GM, Hayes J, Howard R, Howes OD, Juruena MF, Lam RW, Lawrie SM, McAllister-Williams H, Marwaha S, Matuskey D, McCutcheon RA, Nutt DJ, Pariante C, Pillinger T, Radhakrishnan R, Rucker J, Selvaraj S, Stokes P, Upthegrove R, Yalin N, Yatham L, Young AH, Zahn R, Cowen PJet al., 2023, A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression., Mol Psychiatry

Journal article

Parker CA, Nutt DJ, Tyacke RJ, 2023, Imidazoline-I2 PET Tracers in Neuroimaging., Int J Mol Sci, Vol: 24

Targeting neuroinflammation, and in particular, microglial activation and astrocytosis, is a current area of the focus of new treatment interventions for a number of neurodegenerative disorders. Probing the roles of microglia and astrocytes in human disease requires the development of useful tools, such as PET imaging tools that are specific for the cell type(s) of interest. This review concentrates on the recent advances in the development of Imidazoline2 binding site (I2BS) PET tracers, which are purported to target astrocytes, and hence could represent key clinical imaging tools for targeting astrocytes in neurodegenerative disease. Five PET tracers for the I2BS are described in this review, with only one (11C-BU99008) being currently validated to GMP for clinical use, and data reported from healthy volunteers, Alzheimer's disease patients, and Parkinson's disease patients. The clinical data utilising 11C-BU99008 have revealed the potential early involvement of astrogliosis in neurodegeneration that might precede the activation of microglia, which, if confirmed, could provide a vital new means for potentially targeting neurodegeneration earlier in the disease course.

Journal article

Timmermann Slater CB, Roseman L, Haridas S, Rosas F, Luan L, Kettner H, Martell J, Erritzoe D, Tagliazucchi E, Pallavicini C, Girn M, Alamia A, Leech R, Carhart-Harris Ret al., 2023, Human brain effects of DMT assessed via EEG-fMRI, Proceedings of the National Academy of Sciences of USA, Vol: 120, Pages: 1-12, ISSN: 0027-8424

Psychedelics have attracted medical interest, but their effects on human brain function are incompletely understood. In a comprehensive, within-subjects, placebo-controlled design, we acquired multimodal neuroimaging [i.e., EEG-fMRI (electroencephalography-functional MRI)] data to assess the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT) on brain function in 20 healthy volunteers. Simultaneous EEG-fMRI was acquired prior to, during, and after a bolus IV administration of 20 mg DMT, and, separately, placebo. At dosages consistent with the present study, DMT, a serotonin 2A receptor (5-HT2AR) agonist, induces a deeply immersive and radically altered state of consciousness. DMT is thus a useful research tool for probing the neural correlates of conscious experience. Here, fMRI results revealed robust increases in global functional connectivity (GFC), network disintegration and desegregation, and a compression of the principal cortical gradient under DMT. GFC × subjective intensity maps correlated with independent positron emission tomography (PET)-derived 5-HT2AR maps, and both overlapped with meta-analytical data implying human-specific psychological functions. Changes in major EEG-measured neurophysiological properties correlated with specific changes in various fMRI metrics, enriching our understanding of the neural basis of DMT’s effects. The present findings advance on previous work by confirming a predominant action of DMT—and likely other 5-HT2AR agonist psychedelics—on the brain’s transmodal association pole, i.e., the neurodevelopmentally and evolutionarily recent cortex that is associated with species-specific psychological advancements, and high expression of 5-HT2A receptors.

Journal article

Vamvakopoulou IA, Narine KAD, Campbell I, Dyck JRB, Nutt DJet al., 2023, Mescaline: The forgotten psychedelic*, NEUROPHARMACOLOGY, Vol: 222, ISSN: 0028-3908

Journal article

Singleton SP, Luppi AI, Carhart-Harris RL, Cruzat J, Roseman L, Nutt DJ, Deco G, Kringelbach ML, Stamatakis EA, Kuceyeski Aet al., 2022, Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape, NATURE COMMUNICATIONS, Vol: 13

Journal article

Vohryzek J, Cabral J, Lord L-D, Fernandes H, Roseman L, Nutt D, Carhart-Harris R, Deco G, Kringelbach Met al., 2022, Brain dynamics predictive of response to psilocybin for treatment-resistant depression

<jats:title>Abstract</jats:title> <jats:p>Psilocybin therapy for depression has started to show promise, yet the underlying causal mechanisms are not currently known. Here we leveraged the differential outcome in responders and non-responders to psilocybin (10mg and 25mg, 7 days apart) therapy for depression - to gain new insights into regions and networks implicated in the restoration of healthy brain dynamics. We used whole-brain modelling to fit the spatiotemporal brain dynamics at rest in both responders and non-responders before treatment. Dynamic sensitivity analysis of systematic perturbation of these models enabled us to identify specific brain regions implicated in a transition from a depressive brain state to a heathy one. Binarizing the sample into treatment responders (&gt; 50% reduction in depressive symptoms) versus non-responders enabled us to identify a subset of regions implicated in this change. Interestingly, these regions correlate with in vivo density maps of serotonin receptors 5-HT<jats:sub>2A</jats:sub> and 5-HT<jats:sub>1A</jats:sub>, which psilocin, the active metabolite of psilocybin, has an appreciable affinity for, and where it acts as a full-to-partial agonist. Serotonergic transmission has long been associated with depression and our findings provide causal mechanistic evidence for the role of brain regions in the recovery from depression via psilocybin.</jats:p>

Journal article

Nutt DJ, Tyacke RJ, Spriggs M, Jacoby V, Borthwick AD, Belelli Det al., 2022, Functional Alternatives to Alcohol, NUTRIENTS, Vol: 14

Journal article

Bourke SL, Schlag AK, O'Sullivan SE, Nutt DJ, Finn DPet al., 2022, Cannabinoids and the endocannabinoid system in fibromyalgia: A review of preclinical and clinical research, PHARMACOLOGY & THERAPEUTICS, Vol: 240, ISSN: 0163-7258

Journal article

Wall MB, Freeman TP, Hindocha C, Demetriou L, Ertl N, Freeman AM, Jones APM, Lawn W, Pope R, Mokrysz C, Solomons D, Statton B, Walker HR, Yamamori Y, Yang Z, Yim JLL, Nutt DJ, Howes OD, Curran HV, Bloomfield MAPet al., 2022, Individual and combined effects of cannabidiol and Delta(9)-tetrahydrocannabinol on striato-cortical connectivity in the human brain, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 732-744, ISSN: 0269-8811

Journal article

Hayes A, McGonigle J, Elliott R, Ersche K, Flechais R, Orban C, Murphy A, Smith D, Suckling J, Taylor E, Deakin JF, Robbins T, Nutt D, Lingford-Hughes A, Paterson Let al., 2022, The Relationship Between Reward and Impulsivity in Substance Dependence: An fMRI Study, Publisher: ELSEVIER SCIENCE INC, Pages: S103-S103, ISSN: 0006-3223

Conference paper

Daws R, Timmermann C, Giribaldi B, Sexton J, Wall M, Erritzoe D, Roseman L, Nutt D, Carhart-Harris Ret al., 2022, Increased global integration in the brain after psilocybin therapy for depression, Nature Medicine, Vol: 28, ISSN: 1078-8956

Psilocybin therapy shows antidepressant potential, but its therapeutic actions are not well understood. We assessed the sub-acute impact of psilocybin on brain function in two clinical trials of depression. The first was an open-label trial of orally administered psilocybin (10mg and 25mg, 7 days apart) in treatment-resistant depression (TRD). fMRI was recorded at baseline and one day after the 25mg dose. Beck’s depression inventory (BDI) was the primary outcome measure (MR/J00460X/1). The second trial was a double-blind phase 2 randomised control trial (DB-RCT) comparing psilocybin therapy with escitalopram. Major depressive disorder (MDD) patients received either: 2 x 25mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily placebo (‘psilocybin-arm’); or 2 x 1mg oral psilocybin, 3 weeks apart, plus 6 weeks of daily escitalopram [10-20mg] (‘escitalopram-arm’). fMRI wasrecorded at baseline and 3 weeks after the 2nd psilocybin dose (NCT03429075). In both trials, the antidepressant response to psilocybin was rapid, sustained and correlated with decreases in functional MRI (fMRI) brain network modularity, implying that psilocybin’s antidepressant action may depend on a global increase in brainnetwork integration. Network cartography analyses indicated that 5-HT2A receptor rich higher-order functional networks became more functionally inter-connected and flexible post psilocybin. The antidepressant response to escitalopram was milder and no changes in brain network organisation 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.

Journal article

Murphy R, Kettner HS, Zeifman R, Giribaldi B, Kartner L, Martell J, Read T, Murphy-Beiner A, Baker Jones M, Nutt D, Erritzoe D, Watts R, Carhart-Harris Ret al., 2022, Therapeutic alliance and rapport modulate responses to psilocybin assisted therapy for depression, Frontiers in Pharmacology, Vol: 12, Pages: 1-19, ISSN: 1663-9812

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, three-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 six 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, R2 = 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 o

Journal article

Livingston NR, Calsolaro V, Hinz R, Nowell J, Raza S, Gentleman S, Tyacke RJ, Myers J, Venkataraman AV, Perneczky R, Gunn RN, Rabiner EA, Parker CA, Murphy PS, Wren PB, Nutt DJ, Matthews PM, Edison Pet al., 2022, Relationship between astrocyte reactivity, using novel C-11-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals, MOLECULAR PSYCHIATRY, Vol: 27, Pages: 2019-2029, ISSN: 1359-4184

Journal article

Schlag AK, Aday J, Salam I, Neill JC, Nutt DJet al., 2022, Adverse effects of psychedelics: From anecdotes and misinformation to systematic science, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 258-272, ISSN: 0269-8811

Journal article

Nutt D, 2022, Why doctors have a moral imperative to prescribe and support medical cannabis-an essay by David Nutt, BMJ-BRITISH MEDICAL JOURNAL, Vol: 376, ISSN: 0959-535X

Journal article

Wall M, Lam C, Ertl N, Kaelen M, Roseman L, Nutt D, Carhart-Harris Ret al., 2021, The effect of psilocybin therapy for depression on low-frequency brain activity in response to music, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S649-S649, ISSN: 0924-977X

Conference paper

Ertl N, Wall M, Pope R, Freeman T, Demetriou L, Yang Z, Solomons D, Mokrysz C, Hindocha C, Lawn W, Jones A, Statton B, Walker H, Yamamori Y, Ying JLL, Bloomfield M, Freeman A, Howes O, Nutt D, Curran HVet al., 2021, Effects of cannabidiol (CBD) alone and combined with Delta 9-tetrahydrocannabinol (THC) on functional connectivity of the pain-matrix, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S429-S429, ISSN: 0924-977X

Conference paper

Zafar RR, Erritzoe D, Wall MB, Myers J, Nutt DJet al., 2021, Dopamine D3 Receptor antagonism in alcohol dependence: A case-control functional Imaging study, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S448-S449, ISSN: 0924-977X

Conference paper

Douglass H, Spriggs MJ, Park RJ, Read T, Danby JL, De Magalhaes FJC, Alderton KL, Lafrance A, Nicholls DE, Erritzoe D, Nutt DJ, Carhart-Harris RLet al., 2021, Study protocol: psilocybin as a treatment for anorexia nervosa: a pilot study, 34th European-College-of-Neuropsychopharmacology (ECNP) Congress on Early Career Scientists in Europe, Publisher: ELSEVIER, Pages: S257-S258, ISSN: 0924-977X

Conference paper

Walsh Z, Mollaahmetoglu OM, Rootman J, Golsof S, Keeler J, Marsh B, Nutt DJ, Morgan CJAet al., 2021, Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review, BJPSYCH OPEN, Vol: 8, ISSN: 2056-4724

Journal article

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, Mantyla F-L, Schruers K, Thomson A, Arteaga-Henriquez G, Benedetti F, Cash-Gibson L, Chae WR, De Smedt H, Gold SM, Hoogendijk WJG, Mondragon 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, Pariante CMet al., 2021, A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials, MOLECULAR PSYCHIATRY, Vol: 27, Pages: 1286-1299, ISSN: 1359-4184

Journal article

Sessa B, Aday JS, O'Brien S, Curran HV, Measham F, Higbed L, Nutt DJet al., 2021, Debunking the myth of 'Blue Mondays': No evidence of affect drop after taking clinical MDMA, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 360-367, ISSN: 0269-8811

Journal article

Nutt D, 2021, UK drugs strategy promises to be tough on criminals, but evidence shows this doesn't work, BMJ-BRITISH MEDICAL JOURNAL, Vol: 375, ISSN: 0959-535X

Journal article

Zafar R, Schlag A, Phillips L, Nutt DJet al., 2021, Medical cannabis for severe treatment resistant epilepsy in children: a case-series of 10 patients, BMJ PAEDIATRICS OPEN, Vol: 5

Journal article

Kuc J, Kettner H, Rosas F, Erritzoe D, Haijen E, Kaelen M, Nutt D, Carhart-Harris RLet al., 2021, Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey, Psychopharmacology, Vol: 239, Pages: 1425-1440, ISSN: 0033-3158

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.ObjectivesThe current study aimed to explore the subjective effects of psychedelics when used alongside cannabis.MethodsParticipants (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.ResultsThe 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.ConclusionsResults 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.

Journal article

Nutt D, Hayes A, Fonville L, Zafar R, Palmer EOC, Paterson L, Lingford-Hughes Aet al., 2021, Alcohol and the Brain, NUTRIENTS, Vol: 13

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00497034&limit=30&person=true