Abstract
Psychedelic drugs, including lysergic acid diethylamide and other agonists of the serotonin 2A receptor (5HT2A-R), induce drastic changes in subjective experience, and provide a unique ...opportunity to study the neurobiological basis of consciousness. One of the most notable neurophysiological signatures of psychedelics, increased entropy in spontaneous neural activity, is thought to be of relevance to the psychedelic experience, mediating both acute alterations in consciousness and long-term effects. However, no clear mechanistic explanation for this entropy increase has been put forward so far. We sought to do this here by building upon a recent whole-brain model of serotonergic neuromodulation, to study the entropic effects of 5HT2A-R activation. Our results reproduce the overall entropy increase observed in previous experiments in vivo, providing the first model-based explanation for this phenomenon. We also found that entropy changes were not uniform across the brain: entropy increased in some regions and decreased in others, suggesting a topographical reconfiguration mediated by 5HT2A-R activation. Interestingly, at the whole-brain level, this reconfiguration was not well explained by 5HT2A-R density, but related closely to the topological properties of the brain’s anatomical connectivity. These results help us understand the mechanisms underlying the psychedelic state and, more generally, the pharmacological modulation of whole-brain activity.
Abstract Psychedelic experiences are often compared to “transformative experiences” due to their potential to change how people think and behave. This study empirically examines whether psychedelic ...experiences constitute transformative experiences. Given psychedelics’ prospective applications as treatments for mental health disorders, this study also explores neuroethical issues raised by the possibility of biomedically directed transformation—namely, consent and moral psychopharmacology. To achieve these aims, we used both inductive and deductive coding techniques to analyze transcripts from interviews with 26 participants in psychedelic retreats. Results indicate that psychedelic experiences can constitute transformative experiences. Twenty participants reported experiences or insights that were seemingly inaccessible or impossible to attain if not for the psychoactive effects of psychedelics. All participants besides one reported some change in identity, values, beliefs, desires, and behavior—changes in behavior being the most common. Participants also reported feeling capable deciding to use psychedelics in part due to information seeking prior to their retreats. Finally, several participants reported an enhanced capacity for enacting changes in their lives. Our results underscore both the importance of subjective embodiment to transformation and the role of transformative agency in shaping outcomes of the psychedelic experience. We examine our results relative to neuroethical issues and advocate for centering the person in psychedelic research and neuroethical inquiry about psychedelics to avoid pitfalls associated with psychedelics’ potential as moral psychopharmacological agents.
Abstract Interest in possible clinical uses for psychedelic drugs has grown steadily over the past decade. Although impressive findings from small studies stimulated considerable speculation and ...provided a strong justification for further study of psychedelic treatments, until very recently there was a dearth of high-quality evidence for their efficacy, mechanisms of action, and appropriate treatment models for clinical use. However, during the past 2-3 years, there have been dramatic advances in the field. This presentation will focus on 5 publications in the field of psychedelic medicine that exemplify three important aspects of the recent progress in psychedelic research. (1) There has been a rapid increase in the number and size of controlled clinical trials of various psychedelic treatments. (2) Conceptual models for studying and potentially understanding the therapeutic effect of psychedelics have increased in sophistication and comprehensiveness. And (3) progress has been made toward developing models of treatment that would facilitate access to safe and effective psychedelic treatments, if and when they are approved by regulatory bodies. Although progress has been rapid, the field of psychedelic medicine is still in its infancy. Much more work on these and many other fronts will be necessary to discover what the study of psychedelics can contribute to healthcare and neuroscience. Disclosure of Interest None Declared
Psychedelic Psychiatry Nutt, D.
European psychiatry,
06/2022, Volume:
65, Issue:
S1
Journal Article
Peer reviewed
Open access
The last decade has seen a remarkable resurgence of interest in psychedelic drugs such as psilocybin (from magic mushrooms) LSD and DMT (dimethyl tryptamine – the active ingredient of ayahuasca). ...This has been driven by the discovery that these psychedelics all act agonists of 5-HT2A receptors. Human imaging studies have revealed this action leads to profound alterations in brain measures of activity particularly in terms of increased entropy of EEG MEG and fMRI signals and reduced within-network, but increased between-network, connectivity. In addition they all can increase synaptic growth and brain plasticity. These findings not only explain the subjective nature of the psychedelic experience but also have implications for the treatment of internalising disorders such as depression addiction anorexia and OCD that are characterised by increased within network connectivity especially of the default mode network. Subsequent trials, particularly of psilocybin, in these disorders has revealed significant clinical benefits from even just a single administration. A number of companies have now been set up to extend these discoveries with regulatory-level trials that could result in market authorisations within a few years. My talk will explore these brain mechanisms and clinical data and discuss the potential place of psychedelic medicine in the future of psychiatry. Disclosure I am an advisor to Compass pathways and Beckley Psytec two companies that are developing psychedelics for depression and other psychiatric indications. Several members of my research group receive support from these companies and also from Small Pharma.
Abstract It has been proposed that psychedelics promote wellbeing through spiritual-type transformations, involving changes in metaphysical beliefs. Past empirical research shows a link between the ...use of psychedelics and the endorsement of non-physicalist metaphysical beliefs. However, non-physicalist beliefs encompass a wide range of metaphysical ideas, and their links to wellbeing and psychedelics use remain unclear. We utilized a cross-sectional Internet survey to probe the metaphysical beliefs of participants ( N = 701) with past experience of classical psychedelics, using a novel 42-item questionnaire (Core Metaphysical Beliefs, CMB), encompassing a wide range of metaphysical beliefs. Factor analysis of CMB revealed two factors, Idealism and Materialism. In network analyses, Idealism was linked to psychological insight in a past psychedelic experience ( E = 0.24) and average use of psychedelics ( E = 0.16), and predicted wellbeing ( E s = 0.13 and 0.22). Mediation analyses showed an indirect link from past psychedelics use through Idealism to wellbeing ( p s ≤ .005). Non-Physicalist Beliefs or Materialism were not significant mediators. The results indicate that Idealism specifically, not non-physicalist beliefs generally, mediate a link between the use of psychedelics and wellbeing. Future research is required to establish whether the link is causal, and to understand what the Idealism factor means.
The current standard of care in most uses of psychedelic medicines for the treatment of psychiatric indications includes the provision of a supportive therapeutic context before, during, and after ...drug administration. A diversity of psychedelic-assisted psychotherapy (PAP) models has been created to meet this need. The current article briefly reviews the strengths and limitations of these models, which are divided into basic support models and EBT-inclusive therapy models. It then discusses several shortcomings both types of models share, including a lack of adequate attention to embodied and relational elements of treatment, and insufficient attention to ethical concerns. The article then introduces the EMBARK model, a transdiagnostic, trans-drug framework for the provision of supportive psychotherapy in PAP clinical trials and the training of study therapists. EMBARK was designed to overcome challenges that prior models have had in conceptualizing therapeutic change in psychedelic treatment, incorporating elements of non-psychedelic evidence-based therapies, incorporating therapists’ prior skills and clinical orientations, delimiting therapist interventions for research standardization, and determining specific factors that contribute to treatment outcomes. The article explains EMBARK’s six clinical domains, which represent parallel conceptualizations of how therapists may support therapeutic benefit in PAP treatment, and its four care cornerstones, which reflect therapists’ broad ethical responsibility to participants. The article describes how these elements of the model come together to structure and inform therapeutic interventions during preparation, medicine, and integration sessions. Additionally, the article will discuss how EMBARK therapist training is organized and conducted. Finally, it will demonstrate the broad applicability of EMBARK by describing several current and upcoming PAP clinical trials that have adopted it as the therapeutic frame.
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