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Journal articleSpriggs MJ, Giribaldi B, Lyons T, et al., 2022,
Body mass index (BMI) does not predict responses to psilocybin.
, J PsychopharmacolBACKGROUND: 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.
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Journal articleVamvakopoulou IA, Narine KAD, Campbell I, et al., 2022,
Mescaline: The forgotten psychedelic.
, Neuropharmacology, Vol: 222INTRODUCTION: Mescaline (3,4,5-trimethoxyphenethylamine) is one of the oldest hallucinogens, with evidence of use dating back 5700 years. Mescaline is a naturally occurring alkaloid found in cacti, mainly in the peyote cactus (Lophophora williamsii) and in the cacti of the Echinopsis genus. Since the prohibition of psychoactive substances in the early 70s, research on mescaline and other classical psychedelics has been limited. OBJECTIVES: This article aims to review the pharmacology and behavioural effects of mescaline, focusing on preclinical and clinical research. FINDINGS: Mescaline is a serotonin 5HT2A/2C receptor agonist, with its main hallucinogenic effects being mediated via its 5HT2A receptor agonist action. It also exerts effects via agonist binding at α1A/2A noradrenaline and D1/2/3 dopamine receptors. Overall, mescaline has anxiolytic-like effects in animals and increases prosocial behaviour, locomotion, and response reactivity. In humans, mescaline can induce euphoria, hallucinations, improvements in well-being and mental health conditions, and psychotomimetic effects in a naturalistic or religious setting. CONCLUSION: The pharmacological mechanisms of mescaline are similar to those of other classical psychedelics, like psilocybin and lysergic acid diethylamide (LSD). Mescaline appears to be safe to consume, with most intoxications being mild and easily treatable. Improvement in mental well-being and its ability to overcome alcoholism render mescaline potentially beneficial in clinical settings. This article is part of the Special Issue on 'Psilocybin Research'.
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Journal articleSingleton SP, Luppi AI, Carhart-Harris RL, et al., 2022,
Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape
, NATURE COMMUNICATIONS, Vol: 13 -
Journal articleNutt D, Spriggs M, Erritzoe D, 2022,
Psychedelics therapeutics: What we know, what we think, and what we need to research.
, NeuropharmacologyPsychedelic therapy is perhaps the most exciting new development in psychiatry. Not only does it offer a radical new approach to treatment where mainstream approaches have proven ineffective, but the growing evidence for transdiagnostic efficacy is eliciting a re-think of current diagnostic and symptom-specific approaches to psychiatry. This excitement has led to a massive investment in this field with many tens of new pharmaceutical companies being set up to research the effects of known psychedelics and develop new patentable molecules. Whilst this enthusiasm is to be welcomed, it is important that new research is properly grounded in established facts and reflects current knowledge. In this commentary we lay out the knowledge framework that should be taken into account by all researchers innovation this field.
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Journal articleNutt DJ, Tyacke RJ, Spriggs M, et al., 2022,
Functional Alternatives to Alcohol
, NUTRIENTS, Vol: 14 -
Journal articleWatts R, Kettner H, Geerts D, et al., 2022,
The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world
, PSYCHOPHARMACOLOGY, Vol: 239, Pages: 3461-3483, ISSN: 0033-3158 -
Journal articleNygart 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 -
Journal articleGirn M, Roseman L, Bernhardt B, et al., 2022,
Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex
, NEUROIMAGE, Vol: 256, ISSN: 1053-8119- Author Web Link
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Journal articleLuppi AI, Hansen JY, Adapa R, et al., 2022,
Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape
<jats:title>Abstract</jats:title><jats:p>To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 18 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 7 different mind-altering drugs including anaesthetics, psychedelics, and cognitive enhancers. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. Intriguingly, the effects of both anaesthetics and psychedelics on brain function, though opposite, are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.</jats:p>
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Journal articleHipólito I, Mago J, Rosas F, et al., 2022,
Pattern Breaking: A Complex Systems Approach to Psychedelic Medicine
<p>There is growing evidence for the safety and efficacy of psychedelic therapy in mental health care. What is less understood however, is how psychedelics act to yield therapeutic results. In this paper we propose that psychedelics act as destabilisers — both in a psychological and a neurophysiological sense. Our proposed framework builds on the ‘entropic brain’ hypothesis, according to which psychedelics increase the entropy of spontaneous cortical activity and, in parallel, the richness or depth of content of psychological experience. The so-called ‘RElaxed Beliefs Under pSychedelics’ (REBUS) model is a predictive-coding inspired extension to this hypothesis, which states that psychedelics’ entropic action is paralleled by a relaxation of prior assumptions. Here we adopt a complex systems theory (CST) perspective, proposing that psychedelics act as destabilisers of excessively reinforced fixed points — or ‘attractors’ — which translates as the breaking of excessively reinforced or overweighted patterns of thinking or behaving. Our CST approach explains how psychedelic-induced increases in brain entropy destabilise neurophysiological set-points that are synonymous with overweighted priors, thereby augmenting and enriching the account given by REBUS. We believe that this perspective helps inspire conceptualisations of psychedelic psychotherapy — bearing relevance both to the peak psychedelic experience and subsequent sub-acute period of potential recovery. We discuss implications for risk mitigation and treatment optimization in psychedelic medicine.</p>
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