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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Contact

 

d.nutt

 
 
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Location

 

Burlington Danes BuildingBurlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

1391 results found

Thurgur H, Lynskey M, Schlag AK, Croser C, Nutt DJ, Iveson Eet al., 2023, Feasibility of a cannabidiol-dominant cannabis-based medicinal product for the treatment of long COVID symptoms: A single-arm open-label feasibility trial., Br J Clin Pharmacol

AIMS: To conduct a single-arm open-label feasibility trial of the safety and tolerability of a full-spectrum cannabidiol (CBD)-dominant cannabis-based medicinal product for treating the symptoms of long COVID. METHODS: The treatment phase ran for a total of 21 weeks, followed by ~3 weeks without the study drug. Participants received up to 3 mL of MediCabilis 5% CBD Oil (50 mg CBD/mL, <2 mg δ-9-tetrahydrocannabinol/mL) per day orally. Monthly patient-reported outcome measures of common symptoms and daily self-report of symptoms were collected via a smartphone app. Key measures of heart rate, activity, sleep and oxygen saturation were assessed using wearable technology. RESULTS: Twelve (1 male, 11 female) individuals diagnosed with long COVID were recruited into the trial. All participants adhered to the treatment protocol for the duration of the study and there were no serious adverse events. Response rates for the research assessments were high with over 90% completion of patient-reported outcome measures and daily self-report. CONCLUSION: The study drug was safe and well-tolerated, demonstrating feasibility of CBD-dominant cannabis-based medicinal products in individuals diagnosed with long COVID. However, there were limitations in research design related to recruitment strategy demonstrating a lack of feasibility in the approach implemented in this study. Future work with larger samples and incorporating a control group are required to test the efficacy of this treatment.

Journal article

Nutt DJ, Peill JM, Weiss B, Godfrey K, Carhart-Harris RL, Erritzoe Det al., 2023, Psilocybin and Other Classic Psychedelics in Depression., Curr Top Behav Neurosci, ISSN: 1866-3370

Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT2A receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences, insightful and emotional breakthroughs as well as mystical-type experiences. When coupled with psychological support, effects can produce a rapid improvement in mood among people with depression that can last for months. In this chapter, we summarise the scientific studies to date that explore the use of psychedelics in depressed individuals, highlighting key clinical, psychological and neuroimaging features of psychedelics that may account for their therapeutic effects. These include alterations in brain entropy that disrupt fixed negative ruminations, a period of post-treatment increased cognitive flexibility, and changes in self-referential psychological processes. Finally, we propose that the brain mechanisms underlying the therapeutic effect of serotonergic psychedelics might be distinct from those underlying classical serotonin reuptake-blocking antidepressants.

Journal article

Nutt DJ, 2023, Pharmacological Dissection of Antipsychotics, BIOLOGICAL PSYCHIATRY, Vol: 94, Pages: 524-525, ISSN: 0006-3223

Journal article

Wall MB, Harding R, Zafar R, Rabiner EA, Nutt DJ, Erritzoe Det al., 2023, Neuroimaging in psychedelic drug development: past, present, and future, MOLECULAR PSYCHIATRY, ISSN: 1359-4184

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 RESEARCH, Vol: 327, ISSN: 0165-1781

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

Szigeti B, Nutt D, Carhart-Harris R, Erritzoe Det al., 2023, The difference between 'placebo group' and 'placebo control': a case study in psychedelic microdosing, Scientific Reports, Vol: 13, Pages: 1-10, ISSN: 2045-2322

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.

Journal article

Szigeti B, Phillips LDD, Nutt D, 2023, Bayesian analysis of real-world data as evidence for drug approval: Remembering Sir Michael Rawlins, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, ISSN: 0306-5251

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, MOLECULAR PSYCHIATRY, ISSN: 1359-4184

Journal article

Parker CAA, Nutt DJJ, Tyacke RJJ, 2023, Imidazoline-I2 PET Tracers in Neuroimaging, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 24, ISSN: 1661-6596

Journal article

Gattuso JJ, Perkins D, Ruffell S, Lawrence AJ, Hoyer D, Jacobson LH, Timmermann C, Castle D, Rossell SL, Downey LA, Pagni BA, Galvao-Coelho NL, Nutt D, Sarris Jet al., 2023, Default Mode Network Modulation by Psychedelics: A Systematic Review, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, Vol: 26, Pages: 155-188, ISSN: 1461-1457

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

Shukuroglou M, Roseman L, Wall M, Nutt D, Kaelen M, Carhart-Harris Ret al., 2023, Changes in music-evoked emotion and ventral striatal functional connectivity after psilocybin therapy for depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 70-79, ISSN: 0269-8811

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

Watts R, Kettner H, Geerts D, Gandy S, Kartner L, Mertens L, Timmermann C, Nour MM, Kaelen M, Nutt D, Carhart-Harris R, Roseman Let al., 2022, The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world, PSYCHOPHARMACOLOGY, Vol: 239, Pages: 3461-3483, ISSN: 0033-3158

Journal article

Vamvakopoulou IA, Fonville L, Hayes A, McGonigle J, Elliott R, Ersche KD, Flechais R, Murphy A, Orban C, Smith DG, Suckling J, Taylor EM, Deakin B, Robbins TW, Nutt D, Lingford-Hughes A, Paterson Let al., 2022, Selective D3 receptor antagonism modulates neural response during negative emotional processing in substance dependence, Frontiers in Psychiatry, Vol: 13, Pages: 1-20, ISSN: 1664-0640

Introduction: Negative affective states contribute to the chronic-relapsingnature of addiction. Mesolimbic dopamine D3 receptors are well placed to modulate emotion and are dysregulated in substance dependence. Selective antagonists might restore dopaminergic hypofunction, thus representing a potential treatment target. We investigated the effects of selective D3 antagonist, GSK598809, on the neural response to negativeemotional processing in substance dependent individuals and healthy controls.Methodology: Functional MRI BOLD response was assessed during an evocative image task, 2h following acute administration of GSK598809 (60mg) or placebo in a multi-site, double-blind, pseudo-randomised, cross-over design. Abstinent drug dependent individuals (DD, n=36) comprising alcohol-only (AO, n=19) and cocaine-alcohol polydrug (PD, n=17) groups, and matched controls (n=32) were presented with aversive and neutral images in a block design (contrast of interest: aversive>neutral). Whole-brain mixed-effects and a priori ROI analyses tested for group and drug effects, with identical models exploring subgroup effects.Results: No group differences in task-related BOLD signal were identified between DD and controls. However, subgroup analysis revealed greater amygdala/insular BOLD signal in PD compared with AO groups. Following drug administration, GSK598809 increased BOLD response across HC and DD groups in thalamus, caudate, putamen, and pallidum, andreduced BOLD response in insular and opercular cortices relative to placebo. Multivariate analyses in a priori ROIs revealed differential effects of D3 antagonism according to subgroup in substantia nigra; GSK598809 increased BOLD response in AO and decreased response in PD groups.Conclusion: Acute GSK598809 modulates the BOLD response to aversive image processing, providing evidence that D3 antagonism may impact emotional regulation. Enhanced BOLD response within D3-rich mesolimbic regions is consistent with its pharmacology a

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

Zhou C, Nutt DJ, Davies SJC, 2022, Visualizing classification of drugs used in psychotic disorders: A 'subway map' representing mechanisms, established classes and informal categories, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 1007-1015, ISSN: 0269-8811

Journal article

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 LMet al., 2022, Alterations in white matter microstructure in alcohol and alcohol-polydrug dependence: Associations with lifetime alcohol and nicotine exposure, ADDICTION BIOLOGY, Vol: 27, ISSN: 1355-6215

Journal article

Mohamed MA, Zeng Z, Gennaro M, Lao-Kaim N, Myers J, Calsolaro V, Femminella G, Tyacke R, Martin-Bastida A, Gunn R, Nutt D, Edison P, Piccini P, Roussakis Aet al., 2022, Astrogliosis in aging and Parkinson’s disease dementia: a new clinical study with 11C-BU99008 PET, Brain Communications, Vol: 4, ISSN: 2632-1297

The role of astrogliosis in the pathology of brain aging and neurodegenerative diseases has recently drawn great attention. Imidazoline-2 binding sites (I2BS) represent a possible target to map the distribution of reactive astrocytes. In this study, we use 11C-BU99008, an I2BS-specific PET radioligand, to image reactive astrocytes in vivo in healthy controls (HCs) andpatients with established Parkinson’s disease dementia (PDD).Eighteen HCs (age: 45−78 years) and six patients with PDD (age: 64−77 years) had one 11C-BU99008 PET-CT scan with arterial input function. All subjects underwent one 3T MRI brain scan to facilitate the analysis of the PET-CT data and to capture individual cerebral atrophy. Regional 11C-BU99008 volumes of distribution (VT) were calculated for each subject by two-tissue compartmental modelling.Positive correlations between 11C-BU99008 VT values and age were found for all tested regions across the brain within HCs (p<0.05); furthermore, multiple regression indicated that aging affects 11C-BU99008 VT values in a region-specific manner. Independent samples t-test indicated that there was no significant group difference in 11C-BU99008 VT values betweenPDD (n=6; mean age = 71.97±4.66 years) and older HCs (n=9; mean age = 71.90±5.51 years).Our dataset shows that astrogliosis is common with aging in a region-specific manner. However, in this set-up, 11C-BU99008 PET cannot differentiate patients with PDD from healthy controls of similar age.

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., 2022, A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products, CANNABIS AND CANNABINOID RESEARCH, Vol: 7, Pages: 482-500, ISSN: 2578-5125

Journal article

Van den Eynde V, Abdelmoemin WR, Abraham MM, Amsterdam JD, Anderson IM, Andrade C, Baker GB, Beekman ATF, Berk M, Birkenhager TK, Blackwell BB, Blier P, Blom MBJ, Bodkin AJ, Cattaneo C, Dantz B, Davidson J, Dunlop BW, Estevez RF, Feinberg SS, Finberg JPM, Fochtmann LJ, Gotlib D, Holt A, Insel TR, Larsen JK, Mago R, Menkes DB, Meyer JM, Nutt DJ, Parker G, Rego MD, Richelson E, Ruhe HG, Saiz-Ruiz J, Stahl SM, Steele T, Thase ME, Ulrich S, van Balkom AJLM, Vieta E, Whyte I, Young AH, Gillman PKet al., 2022, The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression, CNS SPECTRUMS, ISSN: 1092-8529

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 Δ<SUP>9</SUP>-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

Sakal C, Lynskey M, Schlag AK, Nutt DJet al., 2022, Developing a real-world evidence base for prescribed cannabis in the United Kingdom: preliminary findings from Project Twenty21, PSYCHOPHARMACOLOGY, Vol: 239, Pages: 1147-1155, ISSN: 0033-3158

Journal article

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 <SUP>11</SUP>C-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

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