Publications
97 results found
Timmermann Slater CB, Roseman L, Haridas S, et al., 2023, Human brain effects of DMT assessed via EEG-fMRI, Proceedings of the National Academy of Sciences of USA, ISSN: 0027-8424
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
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- Citations: 1
Spriggs MJ, Giribaldi B, Lyons T, et 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.
Erritzoe D, Godlewska BR, Rizzo G, et al., 2022, Brain Serotonin Release Is Reduced in Patients With Depression: A [11C]Cimbi-36 Positron Emission Tomography Study With a d-Amphetamine Challenge., Biol Psychiatry
BACKGROUND: The serotonin hypothesis of depression proposes that diminished serotonergic (5-HT) neurotransmission is causal in the pathophysiology of the disorder. Although the hypothesis is over 50 years old, there is no firm in vivo evidence for diminished 5-HT neurotransmission. We recently demonstrated that the 5-HT2A receptor agonist positron emission tomography (PET) radioligand [11C]Cimbi-36 is sensitive to increases in extracellular 5-HT induced by an acute d-amphetamine challenge. Here we applied [11C]Cimbi-36 PET to compare brain 5-HT release capacity in patients experiencing a major depressive episode (MDE) to that of healthy control subjects (HCs) without depression. METHODS: Seventeen antidepressant-free patients with MDE (3 female/14 male, mean age 44 ± 13 years, Hamilton Depression Rating Scale score 21 ± 4 [range 16-30]) and 20 HCs (3 female/17 male, mean age 32 ± 9 years) underwent 90-minute dynamic [11C]Cimbi-36 PET before and 3 hours after a 0.5-mg/kg oral dose of d-amphetamine. Frontal cortex (main region of interest) 5-HT2A receptor nondisplaceable binding was calculated from kinetic analysis using the multilinear analysis-1 approach with the cerebellum as the reference region. RESULTS: Following d-amphetamine administration, frontal nondisplaceable binding potential (BPND) was significantly reduced in the HC group (1.04 ± 0.31 vs. 0.87 ± 0.24, p < .001) but not in the MDE group (0.97 ± 0.25 vs. 0.92 ± 0.22, not significant). ΔBPND of the MDE group was significantly lower than that of the HC group (HC: 15% ± 14% vs. MDE: 6.5% ± 20%, p = .041). CONCLUSIONS: This first direct assessment of 5-HT release capacity in people with depression provides clear evidence for dysfunctional serotonergic neurotransmission in depression by demonstrating reduced 5-HT release capacity in patients experiencing an MDE.
Nygart VA, Pommerencke LM, Haijen E, et 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
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- Citations: 1
Teixeira PJ, Johnson MW, Timmermann C, et al., 2021, Psychedelics and health behaviour change, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 36, Pages: 12-19, ISSN: 0269-8811
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- Citations: 14
Carhart-Harris RL, Wagner AC, Agrawal M, et 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
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- Citations: 15
Andersen KAA, Carhart-Harris R, Nutt DJ, et al., 2020, Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies, ACTA PSYCHIATRICA SCANDINAVICA, Vol: 143, Pages: 101-118, ISSN: 0001-690X
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- Citations: 66
Stenbaek DS, Madsen MK, Ozenne B, et al., 2020, Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 459-468, ISSN: 0269-8811
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- Citations: 27
Borissova A, Ferguson B, Wall MB, et al., 2020, Acute effects of MDMA on trust, cooperative behaviour and empathy: A double-blind, placebo-controlled experiment, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 35, Pages: 547-555, ISSN: 0269-8811
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- Citations: 7
Nutt D, Erritzoe D, Carhart-Harris R, 2020, Psychedelic Psychiatry's Brave New World, CELL, Vol: 181, Pages: 24-28, ISSN: 0092-8674
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- Citations: 96
Erritzoe D, Ashok AH, Searle GE, et al., 2020, Serotonin release measured in the human brain: A PET study with [11C]CIMBI-36 and d-amphetamine challenge, Neuropsychopharmacology, Vol: 45, Pages: 804-810, ISSN: 0893-133X
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 receptor agonist radioligand, [11C]CIMBI-36, and a d-amphetamine challenge to evaluate synaptic 5-HT changes in the living human brain. Seventeen healthy male volunteers received [11C]CIMBI-36 PET scans before and 3 hours after an oral dose of d-amphetamine (0.5 mg/kg). Dynamic PET data were acquired over 90 minutes, and the total volume of distribution (VT) in the frontal cortex and the cerebellum derived from a kinetic analysis using MA1. The frontal cortex binding potential (BPNDfrontal) was calculated as (VTfrontal/VTcerebellum)-1. BPNDfrontal = 1- (BPNDfrontalpost-dose/ BPNDfrontalbaseline) was used as an index of 5-HT release. Statistical inference was tested by means of a paired Students t-test evaluating a reduction in post-amphetamine [11C]CIMBI-36 BPNDfrontal .Following d-amphetamine administration, [11C]CIMBI-36 BPNDfrontal was reduced by 14 ± 13 % (p = 0.002). Similar effects were observed in other cortical regions examined in an exploratory analysis.[11C]CIMBI-36 binding is sensitive to synaptic serotonin release in the human brain, and when combined with a d-amphetamine challenge, the evaluation of the human brain serotonin system in neuropsychiatric disorders, such as major depression and Parkinson’s disease is enabled.
Erritzoe D, Godlewska BR, Rizzo G, et al., 2019, Brain serotonin release reduced among patients with severe depression: a pet study with [11c]cimbi-36 and d-amphetamine challenge, 32nd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S258-S258, ISSN: 0924-977X
Stenbaek D, Madsen MK, Ozenne B, et al., 2019, Modelling the acute temporal dynamics of psilocybin psychoactive effects; relation to brain serotonin 2a receptor levels, 32nd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S558-S558, ISSN: 0924-977X
Timmermann Slater CB, Roseman L, Schartner M, et al., 2019, Neural correlates of the DMT experience as assessed with multivariate EEG, Scientific Reports, Vol: 9, Pages: 1-13, ISSN: 2045-2322
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 diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.
Nestor LJ, Paterson LM, Murphy A, et al., 2019, Naltrexone differentially modulates the neural correlates of motor impulse control in abstinent alcohol-dependent and poly-substance dependent individuals, European Journal of Neuroscience, Vol: 50, Pages: 2311-2321, ISSN: 0953-816X
Identifying key neural substrates in addiction disorders for targeted drug development remains a major challenge for clinical neuroscience. One emerging target is the opioid system, where substance‐dependent populations demonstrate prefrontal opioid dysregulation that predicts impulsivity and relapse. This may suggest that disturbances to the prefrontal opioid system could confer a risk for relapse in addiction due to weakened “top‐down” control over impulsive behaviour. Naltrexone is currently licensed for alcohol dependence and is also used clinically for impulse control disorders. Using a go/no‐go (GNG) task we examined the effects of acute naltrexone on the neural correlates of successful motor impulse control in abstinent alcoholics (AUD), abstinent poly substance‐dependent (poly‐SUD) individuals, and controls during a randomized double blind placebo controlled fMRI study. In the absence of any differences on GNG task performance, the AUD group showed a significantly greater BOLD response compared to the control group in lateral and medial prefrontal regions during both placebo and naltrexone treatments; effects that were positively correlated with alcohol abstinence. There was also a dissociation in the positive modulating effects of naltrexone in the orbitofrontal cortex (OFC) and anterior insula cortex (AIC) of the AUD and poly‐SUD groups respectively. Self‐reported trait impulsivity in the poly‐SUD group also predicted the effect of naltrexone in the AIC. These results suggest that acute naltrexone differentially amplifies neural responses within two distinct regions of a salience network during successful motor impulse control in abstinent AUD and poly‐SUD groups, which are predicted by trait impulsivity in the poly‐SUD group.
Timmermann C, Roseman L, Schartner M, et al., 2019, Neural correlates of the DMT experience as assessed via multivariate EEG, Publisher: Cold Spring Harbor Laboratory
<jats:title>Abstract</jats:title><jats:p>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 diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the <jats:italic>alpha</jats:italic> and <jats:italic>beta</jats:italic> bands and robustly increased spontaneous signal diversity. Time-referenced analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience, and particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the relevant subjective experience and thus further our understanding of the neurobiological underpinnings of immersive states of consciousness.</jats:p>
Kuypers KPC, Ng L, Erritzoe D, et al., 2019, Microdosing psychedelics: More questions than answers? An overview and suggestions for future research, JOURNAL OF PSYCHOPHARMACOLOGY, ISSN: 0269-8811
Erritzoe D, Godlewska BR, Rizzo G, et al., 2019, Reduced serotonin release in patients with major depression: a PET study with [11C]Cimbi-36 and d-amphetamine challenge, 29th International Symposium on Cerebral Blood Flow, Metabolism and Function / 14th International Conference on Quantification of Brain Function with PET (BRAIN and BRAIN Pet), Publisher: SAGE PUBLICATIONS INC, Pages: 548-549, ISSN: 0271-678X
Madsen MK, Fisher PM, Burmester D, et al., 2019, Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels, NEUROPSYCHOPHARMACOLOGY, Vol: 44, Pages: 1328-1334, ISSN: 0893-133X
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- Citations: 128
Madsen MK, Fisher PM, Burmester D, et al., 2019, Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels (vol 44, pg 1328, 2019), NEUROPSYCHOPHARMACOLOGY, Vol: 44, Pages: 1336-1337, ISSN: 0893-133X
Erritzoe D, Smith J, Fisher PM, et al., 2019, Recreational use of psychedelics is associated with elevated personality trait openness: Exploration of associations with brain serotonin markers., J Psychopharmacol, Pages: 269881119827891-269881119827891
BACKGROUND:: Recent studies have suggested therapeutic benefits of psychedelics for a variety of mental health conditions. The understanding of how single psychedelic administrations can induce long-lasting effects are, in large, still lacking. However, recent studies in both healthy and clinical populations suggest a role for personality changes. AIM:: To test support for some of these plausible mechanisms we evaluated (cross-sectional) associations between recreational use of psychedelics and 3,4-methylene-dioxymethamphetamine (MDMA) and (a) personality measures and (b) key markers of cerebral serotonergic signalling (serotonin transporter and serotonin-2A-receptor binding). METHODS:: In 10 psychedelic-preferring recreational users, 14 MDMA-preferring users and 21 non-using controls, personality was assessed using the 'big five' instrument Revised NEO Personality Inventory (NEO-PI-R). Frontal serotonin transporter and serotonin-2A-receptor binding potentials were quantified using [11C]DASB and [18F]altanserin positron emission tomography, respectively. RESULTS:: Of the five NEO-PI-R traits, only openness to experience scores differed between the three groups; psychedelic-preferring recreational users showing higher openness to experience scores when compared with both MDMA-preferring users and controls. Openness to experience scores were positively associated with lifetime number of psychedelic exposures, and among all MDMA-preferring user/psychedelic-preferring recreational user individuals, frontal serotonin transporter binding - but not frontal serotonin-2A-receptor binding - was positively associated with openness to experience. CONCLUSION:: Our findings from this cross-sectional study support increasing evidence of a positive association between psychedelic experiences and openness to experience, and (a) expands this to the context of 'recreational' psychedelics use, and (b) links serotonergic neurotransmission to openness to experience. A modulation of perso
Madsen MK, Burmester D, Stenbaek DS, et al., 2019, Psilocybin occupancy of brain serotonin 2A receptors correlates with psilocin levels and subjective experience: a [11C]Cimbi-36 PET study in humans, 31st Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER, Pages: S304-S305, ISSN: 0924-977X
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- Citations: 2
Erritzoe D, Roseman L, Nour MM, et al., 2018, Effects of psilocybin therapy on personality structure, Acta Psychiatrica Scandinavica, Vol: 138, Pages: 368-378, ISSN: 1600-0447
ObjectiveTo explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment‐resistant depression (TRD).MethodTwenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and at 3‐month follow‐up using the Revised NEO Personality Inventory (NEO‐PI‐R), the subjective psilocybin experience with Altered State of Consciousness (ASC) scale, and depressive symptoms with QIDS‐SR16.ResultsNeuroticism scores significantly decreased while Extraversion increased following psilocybin therapy. These changes were in the direction of the normative NEO‐PI‐R data and were both predicted, in an exploratory analysis, by the degree of insightfulness experienced during the psilocybin session. Openness scores also significantly increased following psilocybin, whereas Conscientiousness showed trend‐level increases, and Agreeableness did not change.ConclusionOur observation of changes in personality measures after psilocybin therapy was mostly consistent with reports of personality change in relation to conventional antidepressant treatment, although the pronounced increases in Extraversion and Openness might constitute an effect more specific to psychedelic therapy. This needs further exploration in future controlled studies, as do the brain mechanisms of postpsychedelic personality change.
Timmermann C, Timmermann Slater C, Roseman L, et al., 2018, DMT models the near-death experience, Frontiers in Psychology, Vol: 9, ISSN: 1664-1078
Near-death experiences (NDEs) are complex subjective experiences, which have been previously associated with the psychedelic experience and more specifically with the experience induced by the potent serotonergic, N,N-Dimethyltryptamine (DMT). Potential similarities between both subjective states have been noted previously, including the subjective feeling of transcending one’s body and entering an alternative realm, perceiving and communicating with sentient ‘entities’ and themes related to death and dying. In this within-subjects placebo-controled study we aimed to test the similarities between the DMT state and NDEs, by administering DMT and placebo to 13 healthy participants, who then completed a validated and widely used measure of NDEs. Results revealed significant increases in phenomenological features associated with the NDE, following DMT administration compared to placebo. Also, we found significant relationships between the NDE scores and DMT-induced ego-dissolution and mystical-type experiences, as well as a significant association between NDE scores and baseline trait ‘absorption’ and delusional ideation measured at baseline. Furthermore, we found a significant overlap in nearly all of the NDE phenomenological features when comparing DMT-induced NDEs with a matched group of ‘actual’ NDE experiencers. These results reveal a striking similarity between these states that warrants further investigation.
Carhart-Harris RL, Roseman L, Haijen E, et al., 2018, Psychedelics and the essential importance of context, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 32, Pages: 725-731, ISSN: 0269-8811
Szigeti B, Winstock AR, Erritzoe D, et al., 2018, Are ecstasy induced serotonergic alterations overestimated for the majority of users?, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 32, Pages: 741-748, ISSN: 0269-8811
Carhart-Harris RL, Erritzoe D, Haijen E, et al., 2018, Psychedelics and connectedness, PSYCHOPHARMACOLOGY, Vol: 235, Pages: 547-550, ISSN: 0033-3158
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- Citations: 95
Carhart-Harris RL, Bolstridge M, Day CMJ, et al., 2017, Psilocybin with psychological support for treatment-resistant depression: six-month follow-up, Psychopharmacology, Vol: 235, Pages: 399-408, ISSN: 0033-3158
RATIONALE: Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. OBJECTIVES: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. METHODS: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. RESULTS: Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. CONCLUSIONS: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.
Erritzoe D, Richards WA, 2017, Lessons to be learned from early psychedelic therapy in Denmark, NORDIC JOURNAL OF PSYCHIATRY, Vol: 71, Pages: 487-488, ISSN: 0803-9488
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