Imperial College London

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

Faculty of MedicineDepartment of Brain Sciences

The Edmond J Safra Chair in Neuropsychopharmacology
 
 
 
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d.nutt

 
 
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Burlington Danes BuildingBurlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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1366 results found

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

Vamvakopoulou IA, Narine KAD, Campbell I, Dyck JRB, Nutt DJet al., 2022, Mescaline: The forgotten psychedelic., Neuropharmacology, Vol: 222

INTRODUCTION: Mescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, research on mescaline and other classical psychedelics has been limited. OBJECTIVES: This article aims to review the pharmacology and behavioural effects of mescaline, focusing on preclinical and clinical research. FINDINGS: Mescaline is a serotonin 5HT2A/2C receptor agonist, with its main hallucinogenic effects being mediated via its 5HT2A receptor agonist action. It also exerts effects via agonist binding at α1A/2A noradrenaline and D1/2/3 dopamine receptors. Overall, mescaline has anxiolytic-like effects in animals and increases prosocial behaviour, locomotion, and response reactivity. In humans, mescaline can induce euphoria, hallucinations, improvements in well-being and mental health conditions, and psychotomimetic effects in a naturalistic or religious setting. CONCLUSION: The pharmacological mechanisms of mescaline are similar to those of other classical psychedelics, like psilocybin and lysergic acid diethylamide (LSD). Mescaline appears to be safe to consume, with most intoxications being mild and easily treatable. Improvement in mental well-being and its ability to overcome alcoholism render mescaline potentially beneficial in clinical settings. This article is part of the Special Issue on 'Psilocybin Research'.

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

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

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

Spriggs M, Douglass H, Park R, Read T, Danby J, Magalhaes F, Alderton K, Williams T, Blemings A, Lafrance A, Nicholls D, Erritzoe D, Nutt D, Carhart-Harris Ret al., 2021, Study protocol for “Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study", Frontiers in Psychiatry, Vol: 12, Pages: 1-16, ISSN: 1664-0640

Background: Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present 1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and 2) aprotocol for a pilot study of psilocybin-assisted therapy in AN currently underway at Imperial College London. The study aims to assess the feasibility, brain mechanisms and preliminary outcomes of treating anorexia nervosa with psilocybin. Methods: 1) PPI: Across two online focus groups, eleven individuals with lived experience of AN were presented with an overview of the protocol. Their feedback not only identified solutions to possible barriers for future participants, but also helped the research team to better understand the concept of “recovery” from the perspective of those with lived experience. 2) Protocol: Over a 6-week period, twenty female participants (21-65 years old,body mass index (BMI) ³15kg/m2) will receive three oral doses of psilocybin (up to 25 mg) delivered in a therapeutic environment and enveloped by psychological preparation and integration. We will work with participant support networks (care teams and an identified support person) throughout and there will be an extended remote follow-up period of 12 months. Our twofold primary outcomes are 1) psychopathology (Eating Disorder Examination) across the 6-month follow-up and 2) readiness and motivation to engage in recovery (Readiness and Motivation Questionnaire) across the 6-week trial period. Neurophysiological outcome measures will be: 1) functional magnetic resonance imaging (fMRI) brain changes from baseline to 6-week endpoint and 2) post-acute changes in electroencephalography (EEG) activity, including an electrophysiological marker of neuronal plasticity. Discussion: The results of this pilot study will not only shed

Journal article

Mokrysz C, Shaban NDC, Freeman TP, Lawn W, Pope RA, Hindocha C, Freeman A, Wall MB, Bloomfield MAP, Morgan CJA, Nutt DJ, Curran HVet al., 2021, Acute effects of cannabis on speech illusions and psychotic-like symptoms: two studies testing the moderating effects of cannabidiol and adolescence, PSYCHOLOGICAL MEDICINE, Vol: 51, Pages: 2134-2142, ISSN: 0033-2917

Journal article

Carhart-Harris R, Blemings A, Nutt DJ, 2021, Psilocybin for Depression, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 385, Pages: 863-864, ISSN: 0028-4793

Journal article

Scherrer B, Guiraud J, Addolorato G, Aubin H-J, de Bejczy A, Benyamina A, van den Brink W, Caputo F, Dematteis M, Goudriaan AE, Gual A, Kiefer F, Leggio L, Lesch O-M, Maremmani I, Nutt DJ, Paille F, Perney P, Poulnais R, Raffaillac Q, Rehm J, Rolland B, Simon N, Soderpalm B, Sommer WH, Walter H, Spanagel Ret al., 2021, Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy, ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, Vol: 45, Pages: 1722-1734, ISSN: 0145-6008

Journal article

Calsolaro V, Matthews PM, Donat CK, Livingston NR, Femminella GD, Guedes SS, Myers J, Fan Z, Tyacke RJ, Venkataraman AV, Perneczky R, Gunn R, Rabiner EA, Gentleman S, Parker CA, Murphy PS, Wren PB, Hinz R, Sastre M, Nutt DJ, Edison Pet al., 2021, Astrocyte reactivity with late onset cognitive impairment assessed in-vivo using 11C-BU99008 PET and its relationship with amyloid load, Molecular Psychiatry, Vol: 26, Pages: 5848-5855, ISSN: 1359-4184

11C-BU99008 is a novel positron emission tomography (PET) tracer that enables selective imaging of astrocyte reactivity in vivo. To explore astrocyte reactivity associated with Alzheimer’s disease, 11 older, cognitively impaired (CI) subjects and 9 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging (MRI), 18F-florbetaben and 11C-BU99008 PET. The 8 amyloid (Aβ)-positive CI subjects had higher 11C-BU99008 uptake relative to HC across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes. Biological parametric mapping demonstrated a positive voxel-wise neuroanatomical correlation between 11C-BU99008 and 18F-florbetaben. Autoradiography using 3H-BU99008 with post-mortem Alzheimer’s brains confirmed through visual assessment that increased 3H-BU99008 binding localised with the astrocyte protein glial fibrillary acid protein and was not displaced by PiB or florbetaben. This proof-of-concept study provides direct evidence that 11C-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer’s disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high Aβ load. Future studies now can explore how clinical expression of disease varies with astrocyte reactivity.

Journal article

Young AH, Nutt DJ, 2021, More than just smoke: Psychopharmacology of cannabinoids, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 771-772, ISSN: 0269-8811

Journal article

Herlinger KE, Ling YY, Nestor LJ, Pannekoek J, Al Lababidi M, Ertl N, Vanelli F, Chhibbar P, Guerrero E, Canizares S, Akavarapu S, Munafo MR, Lingford-Hughes AR, Nutt DJ, Goldstone APet al., 2021, Comparison of monetary reward anticipation and negative emotional processing in obesity, ex-smokers and abstinent alcohol dependence, 44th Annual Meeting Research Society on Alcoholism / International Society for Behavioral Research on Alcoholism, Publisher: Wiley, Pages: 241A-241A, ISSN: 0145-6008

Conference paper

Palmer EOC, Ward G, Mota B, Tyacke R, Nutt D, Lingford-Hughes A, Ward R, Sastre Met al., 2021, ALCOHOL HANGOVER INDUCES INCREASED NEUROINFLAMMATORY RESPONSE IN A RODENT MODEL, Publisher: WILEY, Pages: 202A-203A, ISSN: 0145-6008

Conference paper

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