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R. Carhart-Harris

Pivotal mental states

January 3, 2022 / Papers, Psychology / Leave a Comment / By / ,

Abstract

This paper introduces a new construct, the ‘pivotal mental state’, which is defined as a hyper-plastic state aiding rapid and deep learning that can mediate psychological transformation. We believe this new construct bears relevance to a broad range of psychological and psychiatric phenomena. We argue that pivotal mental states serve an important evolutionary function, that is, to aid psychological transformation when actual or perceived environmental pressures demand this. We cite evidence that chronic stress and neurotic traits are primers for a pivotal mental state, whereas acute stress can be a trigger. Inspired by research with serotonin 2A receptor agonist psychedelics, we highlight how activity at this particular receptor can robustly and reliably induce pivotal mental states, but we argue that the capacity for pivotal mental states is an inherent property of the human brain itself. Moreover, we hypothesize that serotonergic psychedelics hijack a system that has evolved to mediate rapid and deep learning when its need is sensed. We cite a breadth of evidences linking stress via a variety of inducers, with an upregulated serotonin 2A receptor system (e.g. upregulated availability of and/or binding to the receptor) and acute stress with 5-HT release, which we argue can activate this primed system to induce a pivotal mental state. The pivotal mental state model is multi-level, linking a specific molecular gateway (increased serotonin 2A receptor signaling) with the inception of a hyper-plastic brain and mind state, enhanced rate of associative learning and the potential mediation of a psychological transformation.

Brouwer, A., & Carhart-Harris, R. L. (2021). Pivotal mental states. Journal of psychopharmacology (Oxford, England), 35(4), 319–352. https://doi.org/10.1177/0269881120959637

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A mechanistic model of the neural entropy increase elicited by psychedelic drugs

November 26, 2021 / Neuroscience, Papers / Leave a Comment / By / , , , , , ,

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.

Herzog, R., Mediano, P., Rosas, F. E., Carhart-Harris, R., Perl, Y. S., Tagliazucchi, E., & Cofre, R. (2020). A mechanistic model of the neural entropy increase elicited by psychedelic drugs. Scientific reports, 10(1), 17725. https://doi.org/10.1038/s41598-020-74060-6

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DMT alters cortical travelling waves

November 26, 2021 / DMT, Neuroscience, Papers / Leave a Comment / By / , , , ,

Abstract

Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the ‘precision-weighting of priors’, thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.

Alamia, A., Timmermann, C., Nutt, D. J., VanRullen, R., & Carhart-Harris, R. L. (2020). DMT alters cortical travelling waves. eLife, 9, e59784. https://doi.org/10.7554/eLife.59784

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Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder

November 18, 2021 / Depressive Disorders, Papers, Psychology / Leave a Comment / By / , ,

Abstract

Purpose: Psychedelic therapy is showing promise for a broad range of mental health conditions, indicative of a transdiagnostic action. While the efficacy of symptom-focused treatments for eating disorders (EDs) is limited, improved mental health and psychological wellbeing are thought to contribute to greater treatment outcomes. This study provides the first quantitative exploration of the psychological effects of psychedelics in those reporting an ED diagnosis.

Methods: Prospective, online data were collected from individuals planning to take a psychedelic drug. Twenty-eight participants reporting a lifetime ED diagnosis completed measures of depressive symptomology (Quick Inventory of Depressive Symptomology; QIDS-SR16) and psychological wellbeing (Warwick-Edinburgh Mental Wellbeing Scale; WEMWBS) 1-2 weeks before, and 2 weeks after a psychedelic experience. Twenty-seven of these participants also completed a measure of emotional breakthrough [Emotional Breakthrough Inventory (EBI)] in relation to the acute psychedelic experience.

Results: Bayesian t tests demonstrated overwhelming evidence for improvements in depression and wellbeing scores following the psychedelic experience. Marginal evidence was also found for a correlation between emotional breakthrough and the relevant mental health improvements.

Conclusion: These findings provide supportive evidence for positive psychological aftereffects of a psychedelic experience that are relevant to the treatment of EDs. It is hoped that this will encourage further research and will bolster initiatives to directly examine the safety and efficacy of psychedelic assisted therapy as a treatment of EDs in future clinical trials.

Level of evidence: Level III, cohort study.

Spriggs, M. J., Kettner, H., & Carhart-Harris, R. L. (2021). Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder. Eating and weight disorders : EWD, 26(4), 1265–1270. https://doi.org/10.1007/s40519-020-01000-8

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Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation

November 18, 2021 / Depressive Disorders, Papers, Psychology / Leave a Comment / By / , , , , ,

Abstract

Psychedelic therapy shows promise as a novel intervention for a wide range of mental health concerns but its therapeutic action is incompletely understood. In line with acceptance and commitment therapy’s (ACT’s) transdiagnostic model, qualitative research has suggested that reductions in experiential avoidance are an important component of therapeutic outcomes associated with psychedelics. However, limited research has quantitatively explored the association between decreases in experiential avoidance and therapeutic outcomes associated with psychedelics. Therefore, in two prospective studies, using convenience samples of individuals with plans to use a psychedelic, we explored the impact of psychedelic use on experiential avoidance, depression severity, and suicidal ideation, as well as relationships between changes in these outcomes. Participants (Study 1, N=104; Study 2, N=254) completed self-report questionnaires of depression severity, suicidal ideation, and experiential avoidance: 1) before using a psychedelic (in ceremonial and non-ceremonial contexts), as well as 2) 2-weeks and 3) 4-weeks after psychedelic use. Across both studies, repeated measures ANOVAs indicated significant decreases in experiential avoidance, depression severity, and suicidal ideation after psychedelic use. Furthermore, decreases in experiential avoidance were significantly associated with decreases in depression severity and suicidal ideation. These results suggest that psychedelics may lead to significant decreases in experiential avoidance, depression severity, and suicidal ideation. Additionally, these findings imply that reduced experiential avoidance may be a transdiagnostic mechanism mediating treatment success within psychedelic therapy. We conclude that integrating psychedelics with psychotherapeutic interventions that target experiential avoidance (e.g. ACT) may enhance therapeutic outcomes.

Zeifman, R. J., Wagner, A. C., Watts, R., Kettner, H., Mertens, L. J., & Carhart-Harris, R. L. (2020). Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation. Frontiers in psychiatry, 11, 782. https://doi.org/10.3389/fpsyt.2020.00782

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The Current Status of Psychedelics in Psychiatry

July 29, 2020 / Humanities & Art, LSD, Papers, Publications / By / ,

Abstract

In the 1950s, the Swiss pharmaceutical company Sandoz, which employed the chemist Albert Hofmann, who discovered lysergic acid diethylamide (LSD) and the similar serotonergic psychedelic psilocybin, made these drugs available to the psychiatric research community as the products Delysid and Indocybin, respectively. By the 1960s, these drugs had caused a revolution in brain science and psychiatry because of their widespread use by researchers and clinicians in many Western countries, especially the US. Before LSD was banned, the US National Institutes of Health funded more than 130 studies exploring its clinical utility, with positive results in a range of disorders but particularly anxiety, depression, and alcoholism. However, the displacement of LSD into recreational use and eventual association with the anti-Vietnam war movement led to all psychedelics being banned in the US. This ban became ratified globally under the 1971 UN Convention on narcotics. Since then, research funding, drug production, and the study of psychedelics as clinical agents has been virtually stopped. Until very recently, no companies would manufacture medical-grade psychedelics, which made getting regulatory approval for clinical research—especially clinical trials—very difficult and in some countries (eg, Germany) impossible.

Nutt, D., & Carhart-Harris, R. (2021). The current status of psychedelics in psychiatry. JAMA psychiatry, 78(2), 121-122.; 10.1001/jamapsychiatry.2020.2171
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Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains

February 6, 2022 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers / Leave a Comment / By / , , , ,

Abstract

Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. In addition to the fractal measures, we used a well-established, non-fractal measure of signal complexity and show that they behave similarly. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attenion network. These results show that psychedelic drugs increase the fractal dimension of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.

Varley, T. F., Carhart-Harris, R., Roseman, L., Menon, D. K., & Stamatakis, E. A. (2020). Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains. NeuroImage, 220, 117049. https://doi.org/10.1016/j.neuroimage.2020.117049

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Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains

June 30, 2020 / Anthropology & Sociology, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. In addition to the fractal measures, we used a well-established, non-fractal measure of signal complexity and show that they behave similarly. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attenion network. These results show that psychedelic drugs increase the fractal dimension of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.

Varley, T. F., Carhart-Harris, R., Roseman, L., Menon, D. K., & Stamatakis, E. A. (2020). Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains. NeuroImage, 220, 117049; 10.1016/j.neuroimage.2020.117049
Link to full text

Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains

June 30, 2020 / Anthropology & Sociology, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. In addition to the fractal measures, we used a well-established, non-fractal measure of signal complexity and show that they behave similarly. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attenion network. These results show that psychedelic drugs increase the fractal dimension of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.

Varley, T. F., Carhart-Harris, R., Roseman, L., Menon, D. K., & Stamatakis, E. A. (2020). Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains. NeuroImage, 220, 117049; 10.1016/j.neuroimage.2020.117049
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Spotlight commentary: REBUS and the anarchic brain

June 12, 2020 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / By / ,

Abstract

In ‘REBUS and the Anarchic Brain: Towards a Unified Model of the Brain Action of Psychedelics’, Carhart-Harris and Friston offer an important analysis of what the predictive processing framework has to offer our understanding of psychedelic experiences, providing an invaluable ground for psychedelic psychiatry. While applauding this, we encourage paying greater attention to contextual factors shaping extreme experiences and their sequalae, and suggest that the authors’ comparisons with certain non-psychedelic altered states may overlook more informative parallels that can be drawn elsewhere. Addressing both points will prove fruitful, ultimately, in identifying the mechanisms of action of greatest interest in psychedelic experiences.
Carhart-Harris, R. L., & Friston, K. J. (2019). REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacological reviews, 71(3), 316-344., https://doi.org/10.1093/nc/niaa007
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