David J Nutt

David J Nutt
Imperial College London | Imperial

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226
Publications
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4,385
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Publications

Publications (226)
Article
Full-text available
The consumption of alcohol is associated with well-known health harms and many governments worldwide are actively engaged in devising approaches to reduce them. To this end, a common proposed strategy aims at reducing alcohol consumption. This approach has led to the development of non-alcoholic drinks, which have been especially welcome by younger...
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Background Major depressive disorder is often associated with maladaptive coping strategies, including rumination and thought suppression. Aims To assess the comparative effect of the selective serotonin reuptake inhibitor escitalopram, and the serotonergic psychedelic psilocybin (COMP360), on rumination and thought suppression in major depressive...
Article
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 polyd...
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The role of astrogliosis in the pathology of brain aging and neurodegenerative diseases has recently drawn great attention. Imidazoline-2 binding sites represent a possible target to map the distribution of reactive astrocytes. In this study, we use 11C-BU99008, an imidazoline-2 binding sites-specific PET radioligand, to image reactive astrocytes i...
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Background Prescribed cannabinoids are now legal in the UK and increasingly being used for a variety of conditions, with one of the most frequent conditions being chronic pain. This paper describes the characteristics of individuals seeking prescribed cannabinoids for the treatment of chronic pain in Project Twenty 21, a UK based real world data re...
Preprint
In medical research, the gold standard experimental design is the blinded randomized controlled trial. Despite the central role of blinding, it is rare for trials to assess blinding integrity and to incorporate this information into the interpretation of results. Here we use computational modelling to show that the combination of weak blinding and...
Article
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Background Cannabidiol (CBD) and Δ ⁹ -tetrahydrocannabinol (THC) are the two major constituents of cannabis with contrasting mechanisms of action. THC is the major psychoactive, addiction-promoting, and psychotomimetic compound, while CBD may have opposite effects. The brain effects of these drugs alone and in combination are poorly understood. In...
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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 Participan...
Article
Characterised by chronic widespread musculoskeletal pain, generalised hyperalgesia, and psychological distress, fibromyalgia (FM) is a significant unmet clinical need. The endogenous cannabinoid system plays an important role in modulating both pain and the stress response. Here, we appraise the evidence, from preclinical and clinical studies, for...
Article
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...
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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...
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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 psy...
Preprint
Psychedelic-assisted psychotherapy with psilocybin is an emerging therapy with great promise for depression, and modern psychedelic therapy (PT) methods incorporate music as a key element. Music is an effective emotional/hedonic stimulus that could also be useful in assessing changes in emotional responsiveness following psychedelic therapy. Brain...
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Background: Despite an increasing body of research highlighting their efficacy to treat a broad range of medical conditions, psychedelic drugs remain a controversial issue among the public and politicians, tainted by previous stigmatisation and perceptions of risk and danger. Objective: This narrative review examines the evidence for potential h...
Article
Background Incorporating 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy has shown promise in recent years for treating various mental health conditions, particularly those involving trauma. However, concerns about declines in mood and cognition during the days following dosing, also known as ‘Blue Mondays’, have been raised...
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Objectives To report the findings of a case-series of 10 children suffering with intractable epilepsies in the UK to determine the feasibility for using whole-plant cannabis medicines to treat seizures in children. Setting This study was conducted retrospectively through collecting clinical data from caretakers and clinicians on study outcome vari...
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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...
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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...
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Background: There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in...
Preprint
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Post mortem neuropathology suggests that astrocyte reactivity may play a significant role in neurodegeneration in Alzheimer’s disease. We explored this in vivo using multimodal PET and MRI imaging. Twenty subjects (11 older, cognitively impaired subjects and 9 age-matched healthy controls) underwent brain scanning using the novel reactive astrocyte...
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A loss of GABA signaling is a prevailing hypothesis for the pathogenesis of schizophrenia. Preclinical studies indicate that blockade of the α5 subtype of the GABA receptor (α5-GABAARs) leads to behavioral phenotypes associated with schizophrenia, and postmortem evidence indicates lower hippocampal α5-GABAARs protein and mRNA levels in schizophreni...
Article
Knowledge about the therapeutic potential of medical cannabis has greatly improved over the past decade, with an ever-increasing range of developments in human clinical applications. A growing body of scientific evidence supports the use of medical cannabis products for some therapeutic indications, whilst for others, the evidence base remains disp...
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Favourable regulatory assessments, liberal policy changes, new research centres and substantial commercial investment signal that psychedelic therapy is making a major comeback. Positive findings from modern trials are catalysing developments, but it is questionable whether current confirmatory trials are sufficient for advancing our understanding...
Article
Background Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking. Methods In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a...
Article
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Background: Pharmacological management of chronic neuropathic pain (CNP) still represents a major clinical challenge. Collective harnessing of both the scientific evidence base and clinical experience (of clinicians and patients) can play a key role in informing treatment pathways and contribute to the debate on specific treatments (e.g., cannabino...
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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 in...
Article
Full-text available
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 in...
Article
Background: 3,4-methylenedioxymethamphetamine (MDMA) therapy has qualities that make it potentially well suited for patients with addictions, but this has never been explored in a research study. We present data from the Bristol Imperial MDMA in Alcoholism (BIMA) study. This is the first MDMA addiction study, an open-label safety and tolerability...
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Cannabis has been legalised for medical use in an ever-increasing number of countries. A growing body of scientific evidence supports the use of medical cannabis for a range of therapeutic indications. In parallel with these developments, concerns have been expressed by many prescribers that increased use will lead to patients developing cannabis u...
Article
Background and purpose: Activation of type-2 Imidazoline receptors has been shown to exhibit neuroprotective properties including anti-apoptotic and anti-inflammatory effects, suggesting a potential therapeutic value in Alzheimer's disease (AD). Here, we explored the effects of the Imidazoline-2 ligand BU224 in a model of amyloidosis. Experimenta...
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Background Globally, non-medical heroin use is generating significant public health and social harms, and drug policy about heroin is a controversial field that encompasses many complex issues. Policy responses to illegal heroin markets have varied from militarized eradication of the opium poppy and harsh punishment of users, to more tolerant harm...
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Introduction A recent study has shown that acetate administration leads to a fourfold increase in the transcription of proopiomelanocortin (POMC) mRNA in the hypothalamus. POMC is cleaved to peptides, including β-endorphin, an endogenous opioid (EO) agonist that binds preferentially to the µ-opioid receptor (MOR). We hypothesised that an acetate ch...
Article
Serotonergic psychedelics have been suggested to mirror certain aspects of psychosis, and, more generally, elicit a state of consciousness underpinned by increased entropy of on-going neural activity. We investigated the hypothesis that language produced under the effects of lysergic acid diethylamide (LSD) should exhibit increased entropy and redu...
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Despite the legalisation of cannabis based medicinal products (CBMPs) in the UK in November 2018, today there remains a scarcity of NHS prescriptions, and many patients continue to face unsustainable financial costs to acquire their medicines. Following on from our previous quantitative study highlighting the effectiveness of CBMPs to treat severe...
Preprint
Full-text available
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are two major constituents of cannabis with contrasting mechanisms of action. THC is the major psychoactive, addiction-promoting, and psychotomimetic compound, while CBD may have somewhat opposite effects. The brain effects of these drugs alone and in combination are poorly understood. In particul...
Preprint
Full-text available
Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes such as personality changes. These findings are particularly intriguing given that a decrease of brain entropy is a robust indicator of loss of...
Article
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Animal models have shown that chronic alcohol exposure is associated with persistent neuroadaptations in amygdala synaptic function, whereas human studies have consistently reported amygdala grey‐matter volume (GMV) reductions in alcohol dependent patients (ADP). We hypothesised that chronic alcohol use associated with neuroadaptations may entail a...
Article
Objective To conduct a systematic review of modern‐era (post‐millennium) clinical studies assessing the therapeutic effects of serotonergic psychedelics drugs for mental health conditions. Although the main focus was on efficacy and safety, study characteristics, duration of antidepressants effects across studies, and the role of the subjective dr...
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Although cannabis-based products for medicinal use are now legal in the UK, it is still challenging for patients to gain access, and only very few National Health Service prescriptions have been written to date. This paper attempts to make sense of why the UK lags behind so many other countries which also have legalised medical cannabis. From consu...
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Addiction has been proposed as a 'reward deficient' state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid...
Article
In the 1950s, the Swiss pharmaceutical company Sandoz, which employed the chemist Albert Hofmann, who discovered lysergic acid diethylamide (LSD) and the similar serotonergic psychedelic psilocybin, made these drugs available to the psychiatric research community as the products Delysid and Indocybin, respectively. By the 1960s, these drugs had cau...
Chapter
Seminars in Clinical Psychopharmacology - edited by Peter M. Haddad June 2020
Article
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Background 3,4-Methylenedioxymethamphetamine (MDMA) is being actively researched as an adjunct to psychotherapy. It may be beneficial to trust, empathy and cooperative behaviour due to its acute prosocial effects. Aim To test (a) the acute effects of MDMA on measures of empathy, trust and cooperative behaviour, and (b) subacute changes in mood thr...
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The prevalent spatial distribution of abnormalities reported in cognitive fMRI studies in addiction suggests there are extensive disruptions across whole brain networks. Studies using resting state have reported disruptions in network connectivity in addiction, but these studies have not revealed characteristics of network functioning during critic...
Article
Cambridge Core - Psychiatry and Clinical Psychology - Seminars in Clinical Psychopharmacology - edited by Peter M. Haddad
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Background Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts...
Article
After a legally mandated, decades-long global arrest of research on psychedelic drugs, investigation of psychedelics in the context of psychiatric disorders is yielding exciting results. Outcomes of neuroscience and clinical research into 5-Hydroxytryptamine 2A (5-HT2A) receptor agonists, such as psilocybin, show promise for addressing a range of s...
Article
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Cannabis is the third most used psychoactive substance worldwide. The legal status of cannabis is changing in many Western countries, while we have very limited knowledge of the public health impact of cannabis-related harms. There is a need for a summary of the evidence of harms and risks attributed to cannabis use, in order to inform the definiti...
Article
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In the UK, medical cannabis was approved in November 2018, leading many patients to believe that the medicine would now be available on the NHS. Yet to date, there have been only 12 NHS prescriptions and less than 60 prescriptions in total. In marked contrast a recent patient survey found 1.4 million people are using illicit cannabis for medical pr...
Article
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Background Psilocybin has shown promise as a treatment for depression but its therapeutic mechanisms are not properly understood. In contrast to the presumed actions of antidepressants, we recently found increased amygdala responsiveness to fearful faces one day after open-label treatment with psilocybin (25 mg) in 19 patients with treatment-resist...
Article
This review covers the last twenty years of UK drug control policy leading up to the recent Psychoactive Substances Act. It explores policy decision made in relation to MDMA and mephedrone that not only were associated with increased drug harms overall but also had a significant detrimental effect on the UK research base. The new UK legislation on...
Article
Hangovers represent a major source of distress to the individual and a huge source of economic loss to society. Hangovers and their associated problems have been recognised for thousands of years in both Western and Eastern cultures but only in recent years has there been any scientific research into their mechanisms and treatments. This small revi...
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Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal div...
Article
Positron emission tomography (PET) enables non-invasive estimation of neurotransmitter fluctuations in the living human brain. While these methods have been applied to dopamine and some other transmitters, estimation of 5-hydroxytryptamine (5-HT; Serotonin) release has proved to be challenging. Here we demonstrate the utility of the novel 5-HT2A re...
Article
Introduction: Given the low efficacy of smoking cessation methods, an experimental medicine model indicating smoking abstinence would be of great benefit to the development of new treatments. Hence the sensitivity of cognitive tasks and ambulatory craving measures to smoking abstinence were investigated. Methods: Cognitive tasks and ambulatory r...
Article
Astroglia are multifunctional cells that regulate neuroinflammation and maintain homeostasis within the brain. Astroglial α-synuclein-positive cytoplasmic accumulations have been shown post-mortem in patients with Parkinson's disease and therefore astroglia may play an important role in the initiation and progression of Parkinson's disease. Imidazo...
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Over recent years, there have been several initiatives to gain access to compounds which have been deprioritized by pharmaceutical companies, but which have a data package allowing them to be used in human experimental medicine studies. Such compounds provide an invaluable resource for probing human biology and disease pathology, for improving tran...