Imperial College London

DrDavidErritzoe

Faculty of MedicineDepartment of Brain Sciences

Clinical Senior Lecturer in Psychiatry
 
 
 
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d.erritzoe

 
 
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Centres for Neuropsychopharmacology and Psychedelic ResearchCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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137 results found

Barba T, Kettner H, Radu C, Peill J, Roseman L, Nutt D, Erritzoe D, Carhart-Harris R, Cunha Bet al., 2024, Psychedelics and sexual functioning: a mixed-methods study, Scientific Reports, Vol: 14, ISSN: 2045-2322

Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual functioning and satisfaction are generally regarded as an important aspect of human wellbeing, sexual dysfunction is a common symptom of mental health disorders. It is also a common side effect of selective serotonin reuptake inhibitors (SSRIs), a first line treatment for depression. The aim of the present paper was to investigate the post-acute effects of psychedelics on self-reported sexual functioning, combining data from two independent studies, one large and naturalistic and the other a smaller but controlled clinical trial. Naturalistic use of psychedelics was associated with improvements in several facets of sexual functioning and satisfaction, including improved pleasure and communication during sex, satisfaction with one’s partner and physical appearance. Convergent results were found in a controlled trial of psilocybin therapy versus an SSRI, escitalopram, for depression. In this trial, patients treated with psilocybin reported positive changes in sexual functioning after treatment, while patients treated with escitalopram did not. Despite focusing on different populations and settings, this is the first research study to quantitively investigate the effects of psychedelics on sexual functioning. Results imply a potential positive effect on post-acute sexual functioning and highlight the need for more research on this.

Journal article

Timmermann Slater CB, Zeifman R, Erritzoe D, Nutt D, Carhart-Harris Ret al., 2024, Effects of DMT on mental health outcomes in healthy volunteers, Scientific Reports, ISSN: 2045-2322

Journal article

Barbut Siva J, Barba T, Kettner H, Kuc J, Nutt DJ, Carhart-Harris R, Erritzoe Det al., 2024, Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study., J Psychopharmacol

BACKGROUND: There is growing evidence for the therapeutic effects of psychedelics. However, it is still uncertain how these drugs interact with serotonergic antidepressants (serotonin reuptake inhibitors (SRIs)). OBJECTIVE: This study explores the interaction between psychedelics and SRIs in terms of therapeutic effects. The objective is to compare acute psychedelic effects and subsequent changes in well-being and depressive symptoms among 'SRI -' individuals (not on psychiatric medication) and 'SRI +' individuals (undergoing SRI treatment). METHODS: Using prospective survey data, the study employs multivariate analysis of covariance (MANCOVA) and linear mixed effect models to analyse subjective differences and changes in well-being and depressive symptoms pre- and post-psychedelic experiences. RESULTS: Results indicate that 'SRI -' participants experience significantly more intense subjective effects compared to 'SRI +' participants (F = 3.200, p = 0.016) in MANCOVA analysis. Further analysis reveals 'SRI -' individuals report stronger mystical (18.2% higher, p = 0.048), challenging (50.9% higher, p = 0.001) and emotional breakthrough experiences (31.9% higher, p = 0.02) than 'SRI +' individuals. No differences are observed in drug-induced visual effects (p = 0.19). Both groups exhibited similar improvements in well-being and depressive symptoms after the psychedelic experience. CONCLUSION: Individuals presumed to be on serotonergic antidepressants during psychedelic use display reduced subjective effects but similar antidepressant effects compared to those not undergoing SRI treatment. Further controlled research is needed to comprehend the interplay between serotonergic antidepressants and psychedelics, illuminating potential therapeutic benefits and limitations in clinical contexts.

Journal article

Luan LX, Eckernäs E, Ashton M, Rosas FE, Uthaug MV, Bartha A, Jagger S, Gascon-Perai K, Gomes L, Nutt DJ, Erritzøe D, Carhart-Harris RL, Timmermann Cet al., 2024, Psychological and physiological effects of extended DMT., J Psychopharmacol, Vol: 38, Pages: 56-67

N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that induces a rapid and transient altered state of consciousness when inhaled or injected via bolus administration. Its marked and novel subjective effects make DMT a powerful tool for the neuroscientific study of consciousness and preliminary results show its potential role in treating mental health conditions. In a within-subjects, placebo-controlled study, we investigated a novel method of DMT administration involving a bolus injection paired with a constant-rate infusion, with the goal of extending the DMT experience. Pharmacokinetic parameters of DMT estimated from plasma data of a previous study of bolus intravenous DMT were used to derive dose regimens necessary to keep subjects in steady levels of immersion into the DMT experience over an extended period of 30 min, and four dose regimens consisting of a bolus loading dose and a slow-rate infusion were tested in eleven healthy volunteers (seven male, four female, mean age ± SD = 37.09 ± 8.93 years). The present method is effective for extending the DMT experience in a stable and tolerable fashion. While subjective effects were maintained over the period of active infusion, anxiety ratings remained low and heart rate habituated within 15 min, indicating psychological and physiological safety of extended DMT. Plasma DMT concentrations increased consistently starting 10 min into DMT administration, whereas psychological effects plateaued into the desired steady state, suggesting the development of acute psychological tolerance to DMT. Taken together, these findings demonstrate the safety and effectiveness of continuous IV DMT administration, laying the groundwork for the further development of this method of administration for basic and clinical research.

Journal article

Luppi AI, Girn M, Rosas FE, Timmermann C, Roseman L, Erritzoe D, Nutt DJ, Stamatakis EA, Spreng RN, Xing L, Huttner WB, Carhart-Harris RLet al., 2024, A role for the serotonin 2A receptor in the expansion and functioning of human transmodal cortex, Brain: a journal of neurology, Vol: 147, Pages: 56-80, ISSN: 0006-8950

Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signaling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization of the cortex follows a unimodal-to-transmodal gradient. Situated at the apex of this processing hierarchy - where it plays a central role in the integrative processes underpinning complex, human-defining cognition - the transmodal cortex has disproportionately expanded across human development and evolution. Notably, the adult human transmodal cortex is especially rich in 5-HT2AR expression, and recent evidence suggests that, during early brain development, 5-HT2AR signaling on neural progenitor cells stimulates their proliferation - a critical process for evolutionarily-relevant cortical expansion. Drawing on multimodal neuroimaging and cross-species investigations, we argue that, by contributing to the expansion of the human cortex, and being prevalent at the apex of its hierarchy in the adult brain, 5-HT2AR signaling plays a major role in both human cortical expansion and functioning. Due to its unique excitatory and downstream cellular effects, neuronal 5-HT2AR agonism promotes neuroplasticity, learning, and cognitive and psychological flexibility in a context-(hyper)sensitive manner with therapeutic potential. Overall, we delineate a dual role of 5-HT2ARs in enabling both the expansion and modulation of the human transmodal cortex.

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

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

Bremler R, Katati N, Shergill P, Erritzoe D, Carhart-Harris Ret al., 2023, Case analysis of long-term negative psychological responses to psychedelics, Scientific Reports, Vol: 13, Pages: 1-15, ISSN: 2045-2322

Recent controversies have arisen regarding claims of uncritical positive regard and hype surrounding psychedelic drugs and their therapeutic potential. Criticisms have included that study designs and reporting styles bias positive over negative outcomes. The present study was motivated by a desire to address this alleged bias by intentionally focusing exclusively on negative outcomes, defined as self-perceived ‘negative’ psychological responses lasting for at least 72 h after psychedelic use. A strong justification for this selective focus was that it might improve our ability to capture otherwise missed cases of negative response, enabling us to validate their existence and better examine their nature, as well as possible causes, which could inspire risk-mitigation strategies. Via advertisements posted on social media, individuals were recruited who reported experiencing negative psychological responses to psychedelics (defined as classic psychedelics plus MDMA) lasting for greater than 72 h since using. Volunteers were directed to an online questionnaire requiring quantitative and qualitative input. A key second phase of this study involved reviewing all of the submitted cases, identifying the most severe—e.g., where new psychiatric diagnoses were made or pre-existing symptoms made worse post psychedelic-use—and inviting these individuals to participate in a semi-structured interview with two members of our research team, during which participant experiences and backgrounds were examined in greater depth. Based on the content of these interviews, a brief summary of each case was compiled, and an explorative thematic analysis was used to identify salient and consistent themes and infer common causes. 32 individuals fully completed an onboarding questionnaire (56% male, 53% < age 25); 37.5% of completers had a psychiatric diagnosis that emerged after their psychedelic experience, and anxiety symptoms arose or worsened in 87%.

Journal article

Garel N, Drury J, Levesque JT, Goyette N, Lehmann A, Looper K, Erritzoe D, Dames S, Turecki G, Rej S, Richard-Devantoy S, Greenway KTet al., 2023, The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression, FRONTIERS IN PSYCHIATRY, Vol: 14, ISSN: 1664-0640

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

Zeifman RJ, Kettner H, Pagni BA, Mallard A, Roberts DE, Erritzoe D, Ross S, Carhart-Harris RLet al., 2023, Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences, Scientific Reports, Vol: 13, Pages: 1-11, ISSN: 2045-2322

Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging experiences and enhances positive experiences associated with psilocybin/LSD. However, limited research has investigated the acute effects of co-use of MDMA and psilocybin/LSD. In a prospective convenience sample (N = 698) of individuals with plans to use psilocybin/LSD, we examined whether co-use of MDMA with psilocybin/LSD (n = 27) is associated with differences in challenging or positive experiences. Challenging experiences were measured using the Challenging Experiences Questionnaire and positive experiences were measured using the Mystical Experience Questionnaire and single-item measures of self-compassion, compassion, love, and gratitude. Potentially confounding variables were identified and included as covariates. Relative to psilocybin/LSD alone, co-use of psilocybin/LSD with a self-reported low (but not medium–high) dose of MDMA was associated with significantly less intense total challenging experiences, grief, and fear, as well as increased self-compassion, love and gratitude. Co-use of psilocybin/LSD and MDMA was not associated with differences in mystical-type experiences or compassion. Findings suggest co-use of MDMA with psilocybin/LSD may buffer against some aspects of challenging experiences and enhance certain positive experiences. Limitations include use of a convenience sample, small sample size, and non-experimental design. Additional studies (including controlled dose–response studies) that examine the effects and safety of co-administering MDMA with psilocybin/LSD (in healthy controls and clinical samples) are warranted an

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

Weiss B, Erritzoe D, Giribaldi B, Nutt DJ, Carhart-Harris RLet al., 2023, A critical evaluation of QIDS-SR-16 using data from a trial of psilocybin therapy versus escitalopram treatment for depression, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 37, Pages: 717-732, ISSN: 0269-8811

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

Rabiner EA, Agnorelli C, Howes O, Nutt DJ, Cowen PJ, Erritzoe Det al., 2023, Reply to: No Clear Evidence of Reduced Brain Serotonin Release Capacity in Patients With Depression, BIOLOGICAL PSYCHIATRY, Vol: 93, Pages: E53-E54, ISSN: 0006-3223

Journal article

Erritzoe D, Godlewska BR, Rizzo G, Searle GE, Agnorelli C, Lewis Y, Ashok AH, Colasanti A, Boura I, Farrell C, Parfitt H, Howes O, Passchier J, Gunn RN, Politis M, Nutt DJ, Cowen PJ, Knudsen GM, Rabiner EAet al., 2023, Brain Serotonin Release Is Reduced in Patients With Depression: A [11C]Cimbi-36 Positron Emission Tomography Study With a d-Amphetamine Challenge, BIOLOGICAL PSYCHIATRY, Vol: 93, Pages: 1089-1098, ISSN: 0006-3223

Journal article

Zafar R, 2023, Psychedelic therapy in the treatment of addiction: the past, present and future, Frontiers in Psychiatry, Vol: 14, Pages: 1-24, ISSN: 1664-0640

Psychedelic therapy has witnessed a resurgence in interest in the last decade from the scientific and medical communities with evidence now building for its safety and efficacy in treating a range of psychiatric disorders including addiction (Nutt, Spriggs and Erritzoe, 2023). In this review we will chart the research investigating the role of these interventions in individuals with addiction beginning with an overview of the current socioeconomic impact of addiction, treatment options, and outcomes. We will start by examining historical studies from the first psychedelic research era of the mid-late 1900s, followed by an overview of the available real-world evidence gathered from naturalistic, observational, and survey-based studies. We will then cover modern-day clinical trials of psychedelic therapies in addiction from first-in-human to phase II clinical trials. Finally, we will provide an overview of the different translational human neuropsychopharmacology techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that can be applied to foster a mechanistic understanding of therapeutic mechanisms. A more granular understanding of the treatment effects of psychedelics will facilitate the optimisation of the psychedelic therapy drug development landscape, and ultimately improve patient outcomes.

Journal article

Weiss B, Wingert A, Erritzoe D, Campbell WKet al., 2023, Prevalence and therapeutic impact of adverse life event reexperiencing under ceremonial ayahuasca, Scientific Reports, Vol: 13, Pages: 1-17, ISSN: 2045-2322

The present study examined the safety and efficacy of the ceremonial use of ayahuasca in relation to reports of heightened life event reexperiencing under psychedelics. The study examined (1) the prevalence of specific types of adverse life event reexperiencing, (2) characteristics predictive of reexperiencing, (3) the psychological character of reexperiencing, and (4) the impact of reexperiencing on mental health. Participants were recruited from three ayahuasca healing and spiritual centers in South and Central America (N = 33 military veterans, 306 non-veterans) using self-report data at three timepoints (Pre-retreat, Post-retreat, 3-months post-retreat). Reexperiencing adverse life events under ayahuasca was common, with women showing particularly high probability of reexperiencing sexual assault, veterans reexperiencing combat-related trauma, and individuals with a self-reported lifetime diagnosis of post-traumatic stress disorder exhibiting a substantively higher prevalence of reexperiencing. Reexperiencing was associated with states of reappraisal, psychological flexibility, and discomfort during ceremony, and incremental reductions in trait neuroticism. Clinical implications of these results for the application of psychedelics to mood and stress disorders are discussed.

Journal article

Weiss B, Ginige I, Shannon L, Giribaldi B, Murphy-Beiner A, Murphy R, Baker-Jones M, Martell J, Nutt DJ, Carhart-Harris RL, Erritzoe Det al., 2023, Personality change in a trial of psilocybin therapy vs escitalopram treatment for depression, Psychological Medicine, ISSN: 0033-2917

Background:Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.Methods:In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.Results:PT was associated with decreases in neuroticism (B = −0.63), introversion (B = −0.38), disagreeableness (B = −0.47), impulsivity (B = −0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = −0.47) and disagreeableness (B = −0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = −0.38), disagreeableness (B = −0.26), impulsivity (B = −0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = −0.46) remaining decreased at month 6. No significant between-condition differences were observed.Conclusions:Personality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.

Journal article

Good M, Joel Z, Benway T, Routledge C, Timmermann C, Erritzoe D, Weaver R, Allen G, Hughes C, Topping H, Bowman A, James Eet al., 2023, Pharmacokinetics of <i>N</i>,<i>N</i>-dimethyltryptamine in Humans, EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, ISSN: 0378-7966

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

Carhart-Harris RL, Chandaria S, Erritzoe DE, Gazzaley A, Girn M, Kettner H, Mediano PAM, Nutt DJ, Rosa FE, Roseman L, Timmermann C, Weiss B, Zeifman RJ, Friston KJet al., 2023, Canalization and plasticity in psychopathology, NEUROPHARMACOLOGY, Vol: 226, ISSN: 0028-3908

Journal article

Nayak SM, Bari BA, Yaden DB, Spriggs MJ, Rosas FE, Peill JM, Giribaldi B, Erritzoe D, Nutt DJ, Carhart-Harris Ret al., 2023, A Bayesian Reanalysis of a Trial of Psilocybin versus Escitalopram for Depression., Psychedelic Med (New Rochelle), Vol: 1, Pages: 18-26

OBJECTIVES: To perform a Bayesian reanalysis of a recent trial of psilocybin (COMP360) versus escitalopram for Major Depressive Disorder (MDD) in order to provide a more informative interpretation of the indeterminate outcome of a previous frequentist analysis. DESIGN: Reanalysis of a two-arm double-blind placebo controlled trial. PARTICIPANTS: Fifty-nine patients with MDD. INTERVENTIONS: Two doses of psilocybin 25mg and daily oral placebo versus daily escitalopram and 2 doses of psilocybin 1mg, with psychological support for both groups. OUTCOME MEASURES: Quick Inventory of Depressive Symptomatology-Self-Report (QIDS SR-16), and three other depression scales as secondary outcomes: HAMD-17, MADRS, and BDI-1A. RESULTS: Using Bayes factors and 'skeptical priors' which bias estimates towards zero, for the hypothesis that psilocybin is superior by any margin, we found indeterminate evidence for QIDS SR-16, strong evidence for BDI-1A and MADRS, and extremely strong evidence for HAMD-17. For the stronger hypothesis that psilocybin is superior by a 'clinically meaningful amount' (using literature defined values of the minimally clinically important difference), we found moderate evidence against it for QIDS SR-16, indeterminate evidence for BDI-1A and MADRS, and moderate evidence supporting it for HAMD-17. Furthermore, across the board we found extremely strong evidence for psilocybin's non-inferiority versus escitalopram. These findings were robust to prior sensitivity analysis. CONCLUSIONS: This Bayesian reanalysis supports the following inferences: 1) that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful--and 2) that psilocybin is almost certainly non-inferior to escitalopram. The present results provide a more precise and nuanced interpretation to previously reported results from this trial, and support the need for further research into the relative efficacy of psilocybin therapy for depression with respe

Journal article

Nutt D, Spriggs M, Erritzoe D, 2023, Psychedelics therapeutics: What we know, what we think, and what we need to research, NEUROPHARMACOLOGY, Vol: 223, ISSN: 0028-3908

Journal article

Zeifman R, Spriggs M, Kettner H, Lyons T, Rosas F, Mediano P, Erritzoe D, Carhart-Harris Ret al., 2023, From Relaxed Beliefs Under Psychedelics (REBUS) to Revised Beliefs After Psychedelics (REBAS), Scientific Reports, ISSN: 2045-2322

Objectives: This was a cross sectional study aimed at describing chest x-ray findings among children hospitalised with clinically diagnosed severe pneumonia and hypoxaemia (SpO2<92%) in three tertiary facilities in Uganda.Methods: We studied chest x-rays of 375 children aged 28 days to 12 years enrolled into the Children’s Oxygen Administration Strategies Trial (COAST)(ISRCTN15622505). Radiologists blinded to the clinical findings reported chest x-rays using the standardized World Health Organization methodology for paediatric chest Xray reporting. We summarised clinical data and chest x-ray findings using descriptive statistics. Chi-square and proportion tests were used to compare proportions and quantile regression compared medians. Results: We found 172, (45.8%) children had radiological pneumonia, 136 (36.3%) normal chest radiographs while 123 (32.8%) non-pneumonia findings, the major one being cardiovascular abnormalities,106 (28.3%); 56 (14.9%) chest radiographs had both pneumonia and other abnormalities. There was no difference in the prevalence of radiological pneumonia, cardiovascular abnormalities, and mortality between the group with severe hypoxaemia (SpO2<80%) and that with mild hypoxaemia (SpO280 to <92%), (95% CI: -13.2,7.1, -6.1,15.9) and -37.2, 20.4) respectively. Conclusion: This study highlights a relatively high prevalence of cardiovascular abnormalities in children who fulfill the WHO clinical criteria for severe pneumonia and have hypoxaemia. We recommend that chest x-ray examinations be routinely done for all children in this population because information concerning cardiovascular and respiratory systems can be obtained in one sitting and guide management better. We hope that these findings can prompt discussions into refining the clinical criteria used to classify and manage pneumonia in children in limited resource settings.

Journal article

Spriggs MJ, Giribaldi B, Lyons T, Rosas FE, Kaertner LS, Buchborn T, Douglass HM, Roseman L, Timmermann C, Erritzoe D, Nutt DJ, Carhart-Harris RLet al., 2022, Body mass index (BMI) does not predict responses to psilocybin, Journal of Clinical Psychopharmacology, Vol: 37, Pages: 107-116, ISSN: 0271-0749

Background:Psilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.Method:Data were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.Results:Results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.Conclusions:These findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.

Journal article

Barba T, Buehler S, Kettner H, Radu C, Cunha BG, Nutt DJ, Erritzoe D, Roseman L, Carhart-Harris Ret al., 2022, Effects of psilocybin versus escitalopram on rumination and thought suppression in depression, BJPSYCH OPEN, Vol: 8, ISSN: 2056-4724

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

Nygart VA, Pommerencke LM, Haijen E, Kettner H, Kaelen M, Mortensen EL, Nutt DJ, Carhart-Harris RL, Erritzoe Det al., 2022, Antidepressant effects of a psychedelic experience in a large prospective naturalistic sample, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 932-942, ISSN: 0269-8811

Journal article

Szigeti B, Nutt D, Carhart-Harris R, Erritzoe Det al., 2022, The difference between 'placebo group' and 'placebo control': a case study in psychedelic microdosing

<p>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.</p>

Journal article

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