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
to

1350 results found

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

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, 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

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, 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, 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

Goldstone AP, Ling YY, Nestor LJ, Pannekoek JN, Vanelli F, Herlinger K, Ertl N, Al-Lababidi M, Chhibbar P, Guerrero E, Akavarapu S, Canizares S, Munafo MR, Lingford-Hughes AR, Nutt DJet al., 2021, EFFECT OF ACUTE DESACYL GHRELIN ADMINISTRATION ON EATING AND ADDICTIVE BEHAVIOURS: THE GUT HORMONE IN ADDICTION STUDY, Publisher: WILEY, Pages: 51A-51A, ISSN: 0145-6008

Conference paper

Paterson LM, McGonigle J, Murphy A, Giribaldi B, Elliott R, Ersche KD, Flechais R, Orban C, Smith DG, Suckling J, Taylor EM, Deakin JFW, Robbins TW, Nutt DJ, Lingford-Hughes ARet al., 2021, INVESTIGATING NEURAL CORRELATES OF SUBSTANCE DEPENDENCE AND THEIR PHARMACOLOGICAL MODULATION; NEW AVENUES TO TREATMENT AND PREDICTORS OF RELAPSE, Publisher: WILEY, Pages: 20A-20A, ISSN: 0145-6008

Conference paper

Nutt DJ, de Wit H, 2021, Putting the MD back into MDMA, NATURE MEDICINE, Vol: 27, Pages: 950-951, ISSN: 1078-8956

Journal article

Rolles S, Schlag AK, Measham F, Phillips L, Nutt D, Bergsvik D, Rogeberg Oet al., 2021, A multi criteria decision analysis (MCDA) for evaluating and appraising government policy responses to non medical heroin use, INTERNATIONAL JOURNAL OF DRUG POLICY, Vol: 91, ISSN: 0955-3959

Journal article

Singleton SP, Luppi AI, Carhart-Harris RL, Cruzat J, Roseman L, Deco G, Kringelbach ML, Stamatakis EA, Kuceyeski Aet al., 2021, Psychedelics Flatten the brain’s energy landscape: evidence from receptor-informed network control theory

<jats:title>Abstract</jats:title><jats:p>Psychedelics like lysergic acid diethylamide (LSD) and psilocybin offer a powerful window into the function of the human brain and mind, by temporarily altering subjective experience through their neurochemical effects. The RElaxed Beliefs Under Psychedelics (REBUS) model postulates that 5-HT2a receptor agonism allows the brain to explore its dynamic landscape more readily, as suggested by more diverse (entropic) brain activity. Formally, this effect is theorized to correspond to a reduction in the energy required to transition between different brain-states, i.e. a “flattening of the energy landscape.” However, this hypothesis remains thus far untested. Here, we leverage network control theory to map the brain’s energy landscape, by quantifying the energy required to transition between recurrent brain states using previously acquired functional magnetic resonance imaging data under LSD, psilocybin, and placebo. In accordance with the REBUS model, we show that LSD and psilocybin reduce the energy required for brain-state transitions, and, furthermore, that LSD’s reduction in energy correlates with more frequent state transitions and increased entropy of brain-state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors, we demonstrate the specific role of this receptor in flattening the brain’s energy landscape. This work validates fundamental predictions of the REBUS model of psychedelic action. More broadly, by combining receptor-informed network control theory with pharmacological modulation, this work highlights the potential of this approach in studying the impacts of targeted neuropharmacological manipulation on brain activity dynamics.</jats:p><jats:sec><jats:title>Significance Statement</jats:title><jats:p>We present a multi-modal framework for quantifying the effects of two psychedelic drug

Journal article

Schlag AK, O'Sullivan SE, Zafar RR, Nutt DJet al., 2021, Current controversies in medical cannabis: Recent developments in human clinical applications and potential therapeutics, NEUROPHARMACOLOGY, Vol: 191, ISSN: 0028-3908

Journal article

Sakal C, Lynskey M, Schlag AK, Nutt DJet al., 2021, Developing a real-world evidence base for prescribed cannabis in the United Kingdom: preliminary findings from Project Twenty21, PSYCHOPHARMACOLOGY, ISSN: 0033-3158

Journal article

Carhart-Harris RL, Wagner AC, Agrawal M, Kettner H, Rosenbaum JF, Gazzaley A, Nutt DJ, Erritzoe Det al., 2021, Can pragmatic research, real-world data and digital technologies aid the development of psychedelic medicine?, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 6-11, ISSN: 0269-8811

Journal article

Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, Martell J, Blemings A, Erritzoe D, Nutt DJet al., 2021, Trial of Psilocybin versus Escitalopram for Depression, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 384, Pages: 1402-1411, ISSN: 0028-4793

Journal article

Rolles S, Nutt DJ, Schlag AK, 2021, Some Contributions on How to Formulate Drug Policies and Provide Evidence-Based Regulation, AMERICAN JOURNAL OF BIOETHICS, Vol: 21, Pages: 28-31, ISSN: 1526-5161

Journal article

Fonville L, Paterson L, Herlinger K, Hayes A, Hill R, Nutt D, Lingford-Hughes Aet al., 2021, Functional evaluation of NK1 antagonism on cue reactivity in opiate dependence; an fMRI study, Drug and Alcohol Dependence, Vol: 221, Pages: 1-7, ISSN: 0376-8716

BackgroundOpiate addiction is a major health challenge with substantial societal cost. Though harm minimisation strategies have been effective, there is a growing need for new treatments for detoxification and relapse prevention. Preclinical research has found neurokinin 1 (NK1) receptors have prominent effects on opiate reward and reinforcement, and human studies have found NK1 antagonism led to reductions in craving and withdrawal. However, its effect on brain mechanisms in opiate addiction has not yet been examined.MethodsThis study aims to assess the impact of NK1 antagonist aprepitant on heroin cue-elicited changes in blood-oxygenation level dependent (BOLD) signal in opiate dependent individuals undergoing detoxification. Participants will attend two scanning sessions and receive a single dose of aprepitant (320 mg) and a placebo in a randomised, cross-over design. During functional magnetic resonance imaging participants will undergo two runs of a cue reactivity task, which consists of passive viewing of drug cues or neutral cues in a block design fashion. We hypothesise that NK1 antagonism will attenuate the BOLD response to drug cues in the caudate nucleus and amygdala. Regions of interest were selected based on NK1 receptor density and their role in cue reactivity and craving.

Journal article

Nutt DJ, Phillips LD, Barnes MP, Brander B, Curran HV, Fayaz A, Finn DP, Horsted T, Moltke J, Sakal C, Sharon H, O'Sullivan SE, Williams T, Zorn G, Schlag AKet al., 2021, A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products, CANNABIS AND CANNABINOID RESEARCH, ISSN: 2578-5125

Journal article

Szigeti B, Kartner L, Blemings A, Rosas F, Feilding A, Nutt DJ, Carhart-Harris RL, Erritzoe Det al., 2021, Self-blinding citizen science to explore psychedelic microdosing, eLife, Vol: 10, Pages: 1-26, ISSN: 2050-084X

Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.

Journal article

Gougoulaki M, Lewis G, Nutt DJ, Peters TJ, Wiles NJ, Lewis Get al., 2021, Sex differences in depressive symptoms and tolerability after treatment with selective serotonin reuptake inhibitor antidepressants: Secondary analyses of the GENPOD trial, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 919-927, ISSN: 0269-8811

Journal article

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