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  • 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
    Hipolito I, Mago J, Rosas FE, Carhart-Harris Ret al., 2023,

    Pattern breaking: a complex systems approach to psychedelic medicine

    , Neuroscience of Consciousness, Vol: 2023, ISSN: 2057-2107

    Recent research has demonstrated the potential of psychedelic therapy for mental health care. However, the psychological experience underlying its therapeutic effects remains poorly understood. This paper proposes a framework that suggests psychedelics act as destabilizers, both psychologically and neurophysiologically. Drawing on the ‘entropic brain’ hypothesis and the ‘RElaxed Beliefs Under pSychedelics’ model, this paper focuses on the richness of psychological experience. Through a complex systems theory perspective, we suggest that psychedelics destabilize fixed points or attractors, breaking reinforced patterns of thinking and behaving. Our approach explains how psychedelic-induced increases in brain entropy destabilize neurophysiological set points and lead to new conceptualizations of psychedelic psychotherapy. These insights have important implications for risk mitigation and treatment optimization in psychedelic medicine, both during the peak psychedelic experience and during the subacute period of potential recovery.

  • 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
    Eckernas E, Timmermann C, Carhart-Harris R, Roshammar D, Ashton Met al., 2022,

    Population pharmacokinetic/pharmacodynamic modeling of the psychedelic experience induced by N,N-dimethyltryptamine - Implications for dose considerations

    , CTS-CLINICAL AND TRANSLATIONAL SCIENCE, Vol: 15, Pages: 2928-2937, ISSN: 1752-8054
  • Journal article
    Herzog R, Rosas FE, Whelan R, Fittipaldi S, Santamaria-Garcia H, Cruzat J, Birba A, Moguilner S, Tagliazucchi E, Prado P, Ibanez Aet al., 2022,

    Genuine high-order interactions in brain networks and neurodegeneration

    , Neurobiology of Disease, Vol: 175, Pages: 1-15, ISSN: 0969-9961

    Brain functional networks have been traditionally studied considering only interactions between pairs of regions, neglecting the richer information encoded in higher orders of interactions. In consequence, most of the connectivity studies in neurodegeneration and dementia use standard pairwise metrics. Here, we developed a genuine high-order functional connectivity (HOFC) approach that captures interactions between 3 or more regions across spatiotemporal scales, delivering a more biologically plausible characterization of the pathophysiology of neurodegeneration. We applied HOFC to multimodal (electroencephalography [EEG], and functional magnetic resonance imaging [fMRI]) data from patients diagnosed with behavioral variant of frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and healthy controls. HOFC revealed large effect sizes, which, in comparison to standard pairwise metrics, provided a more accurate and parsimonious characterization of neurodegeneration. The multimodal characterization of neurodegeneration revealed hypo and hyperconnectivity on medium to large-scale brain networks, with a larger contribution of the former. Regions as the amygdala, the insula, and frontal gyrus were associated with both effects, suggesting potential compensatory processes in hub regions. fMRI revealed hypoconnectivity in AD between regions of the default mode, salience, visual, and auditory networks, while in bvFTD between regions of the default mode, salience, and somatomotor networks. EEG revealed hypoconnectivity in the γ band between frontal, limbic, and sensory regions in AD, and in the δ band between frontal, temporal, parietal and posterior areas in bvFTD, suggesting additional pathophysiological processes that fMRI alone can not capture. Classification accuracy was comparable with standard biomarkers and robust against confounders such as sample size, age, education, and motor artifacts (from fMRI and EEG). We conclude that high-order interactions p

  • Journal article
    Cherniak AD, Brulin JG, Mikulincer M, Ostlind S, Carhart-Harris R, Granqvist Pet al., 2022,

    Psychedelic Science of Spirituality and Religion: An Attachment-Informed Agenda Proposal

    , INTERNATIONAL JOURNAL FOR THE PSYCHOLOGY OF RELIGION, ISSN: 1050-8619
  • Journal article
    Kanen JWW, Luo Q, Kandroodi MR, Cardinal RNN, Robbins TWW, Nutt DJJ, Carhart-Harris RLL, den Ouden HEMet al., 2022,

    Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans

    , PSYCHOLOGICAL MEDICINE, ISSN: 0033-2917
  • Journal article
    Zhou K, De Wied D, Carhart-Harris R, Kettner Het al., 2022,

    Predictors Of Hallucinogen Persisting Perception Disorder Symptoms, Delusional Ideation And Magical Thinking Following Naturalistic Psychedelic Use

    <p>OBJECTIVE: Psychedelics have over recent years been subject to a fast-paced growth in scientific research, clinical applications, commercial investment, and substance use trends by the general public. Yet, concerningly little is known about the frequency of adverse side effects of psychedelic use, despite a breadth of anecdotal reports and largely untested assumptions that inform the screening criteria in modern controlled research. This study aimed to evaluate the frequency and predictive factors of specific, enduring, and potentially undesirable, cognitive and perceptual changes, including symptoms related to delusional ideation, magical thinking and hallucinogen persisting perception disorder (HPPD), following real-world psychedelic use in naturalistic settings.METHOD: In this prospective online cohort study, participants were assessed at 3 timepoints: 1 week before (N = 654) a planned psychedelic experience, and at 2 weeks (N = 305) and 4 weeks afterwards (N = 212). Correlational analyses were performed between lifetime psychedelic use, delusional ideation and magical thinking reported at baseline. Additionally, longitudinal changes in these variables were investigated using Friedman’s test, differentiating between novice (≤ 5 times psychedelic use) and experienced users (&amp;gt; 5 times psychedelic use). Further exploratory analyses of longitudinal increases in delusional and magical ideation were performed using logistic regression to identify predictors of change. The frequency of enduring visuo-perceptual effects indicative of HPPD was assessed at the 4 week endpoint. Predictor variables for the occurrence of such effects were determined via logistic regression.RESULTS: Frequency of lifetime psychedelic use was positively, albeit negligibly, correlated with higher baseline levels of delusional ideation rs = .11, p = .01), and magical ideation (rs = .12, p = .003). Contradictorily, delusional ideation was significantly reduced 4 weeks a

  • 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
    Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Páleníček T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia Eet al., 2022,

    Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

    , N Engl J Med, Vol: 387, Pages: 1637-1648

    BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including compariso

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