OPEN Foundation

Consciousness

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

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. NeuroImage220, 117049; 10.1016/j.neuroimage.2020.117049
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Can Psychedelics Alleviate Symptoms of Cluster Headache and Accompanying Mental Health Problems? A Case Report Involving Hawaiian Baby Woodrose

Abstract

Preliminary evidence supports the efficacy of psychedelics in the alleviation of cluster headache and mental health problems. We describe a case of an individual with cluster headache and mood disorder who claims to have benefited from her use of psychedelics. A forty-eight-year-old woman was referred to a private Australian mental health clinic for the management of chronic pain and depression. She reported using Hawaiian baby woodrose to successfully alleviate symptoms of cluster headache and the accompanying mental health problems. Incidental observation also highlighted the potential therapeutic benefits of antiviral therapy. This is the first case report to concurrently examine the analgesic and psycho-spiritual effects of Hawaiian baby woodrose, with results in support of nascent research in this field. The results of this case report highlight the need for further research into the use of psychedelics in the management of cluster headache and mental illness
Johnson, S., & Black, Q. C. (2020). Can Psychedelics Alleviate Symptoms of Cluster Headache and Accompanying Mental Health Problems? A Case Report Involving Hawaiian Baby Woodrose. Journal of Psychoactive Drugs, 1-5., https://doi.org/10.1080/02791072.2020.1762023
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Ayahuasca's 'afterglow': improved mindfulness and cognitive flexibility in ayahuasca drinkers.

Abstract

RATIONALE:
There is a growing body of evidence demonstrating the therapeutic potential of ayahuasca for treating depression and anxiety. However, the mechanisms of action involved in ayahuasca’s therapeutic effects are unclear. Mindfulness and cognitive flexibility may be two possible psychological mechanisms. Like other classic psychedelics, ayahuasca also leads to an ‘afterglow’ effect of improved subjective well-being that persists after the acute effects have subsided. This period may offer a window of increased therapeutic potential.
OBJECTIVE:
To explore changes in mindfulness and cognitive flexibility before and within 24 h after ayahuasca use.METHODS:
Forty-eight participants (54% female) were assessed on measures of mindfulness (Five Facets Mindfulness Questionnaire (FFMQ)), decentering (Experiences Questionnaire (EQ)), and cognitive flexibility (Cognitive Flexibility Scale (CFS)), and completed the Stroop and Wisconsin Picture Card Sorting Task (WPCST) before drinking ayahuasca, and again within 24 h.
RESULTS:
Mindfulness (FFMQ total scores and four of the five mindfulness facets: observe, describe, act with awareness, and non-reactivity) and decentering (EQ) significantly increased in the 24 h after ayahuasca use. Cognitive flexibility (CFS and WPCST) significantly improved in the 24 h after ayahuasca use. Changes in both mindfulness and cognitive flexibility were not influenced by prior ayahuasca use.
CONCLUSIONS:
The present study supports ayahuasca’s ability to enhance mindfulness and further reports changes in cognitive flexibility in the ‘afterglow’ period occur, suggesting both could be possible psychological mechanisms concerning the psychotherapeutic effects of ayahuasca. Given psychological gains occurred regardless of prior ayahuasca use suggests potentially therapeutic effects for both naïve and experienced ayahuasca drinkers.
Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 1-9., https://doi.org/10.1007/s00213-019-05445-3
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Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers.

Abstract

RATIONALE:
There is a growing body of evidence demonstrating the therapeutic potential of ayahuasca for treating depression and anxiety. However, the mechanisms of action involved in ayahuasca’s therapeutic effects are unclear. Mindfulness and cognitive flexibility may be two possible psychological mechanisms. Like other classic psychedelics, ayahuasca also leads to an ‘afterglow’ effect of improved subjective well-being that persists after the acute effects have subsided. This period may offer a window of increased therapeutic potential.
OBJECTIVE:
To explore changes in mindfulness and cognitive flexibility before and within 24 h after ayahuasca use.METHODS:
Forty-eight participants (54% female) were assessed on measures of mindfulness (Five Facets Mindfulness Questionnaire (FFMQ)), decentering (Experiences Questionnaire (EQ)), and cognitive flexibility (Cognitive Flexibility Scale (CFS)), and completed the Stroop and Wisconsin Picture Card Sorting Task (WPCST) before drinking ayahuasca, and again within 24 h.
RESULTS:
Mindfulness (FFMQ total scores and four of the five mindfulness facets: observe, describe, act with awareness, and non-reactivity) and decentering (EQ) significantly increased in the 24 h after ayahuasca use. Cognitive flexibility (CFS and WPCST) significantly improved in the 24 h after ayahuasca use. Changes in both mindfulness and cognitive flexibility were not influenced by prior ayahuasca use.
CONCLUSIONS:
The present study supports ayahuasca’s ability to enhance mindfulness and further reports changes in cognitive flexibility in the ‘afterglow’ period occur, suggesting both could be possible psychological mechanisms concerning the psychotherapeutic effects of ayahuasca. Given psychological gains occurred regardless of prior ayahuasca use suggests potentially therapeutic effects for both naïve and experienced ayahuasca drinkers.
Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 1-9., https://doi.org/10.1007/s00213-019-05445-3
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Decreased directed functional connectivity in the psychedelic state.

Abstract

Neuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the large-scale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data.

Barnett, L., Muthukumaraswamy, S. D., Carhart-Harris, R. L., & Seth, A. K. (2019). Decreased directed functional connectivity in the psychedelic state. NeuroImage, 116462., https://doi.org/10.1016/j.neuroimage.2019.116462
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Microdosing psychedelics: Motivations, subjective effects and harm reduction.

Abstract

BACKGROUND:
In recent years there has been growing media attention on microdosing psychedelics (e.g., LSD, psilocybin). This refers to people routinely taking small doses of psychedelic substances to improve mental health and wellbeing, or to enhance cognitive performance. Research evidence is currently limited. This paper examines microdosing motivations, dosing practices, perceived short-term benefits, unwanted effects, and harm reduction practices.
METHODS:
An international online survey was conducted in 2018 examining people’s experiences of using psychedelics. Eligible participants were aged 16 years or older, had used psychedelics and could comprehend written English. This paper focuses on 525 participants who were microdosing psychedelics at the time of the survey.
RESULTS:
Participants were primarily motivated to microdose to improve mental health (40%), for personal development (31%) and cognitive enhancement (18%). Most were microdosing with psilocybin (55%) or LSD/1P-LSD (48%). Principal components analysis generated three factors examining perceived short-term benefits of microdosing: improved mood and anxiety, enhanced connection to others and environment, and cognitive enhancement; and three factors examining negative and potentially unwanted effects: stronger-than-expected psychedelic effects, anxiety-related effects, and physical adverse effects. Most participants (78%) reported at least one harm reduction practice they routinely performed while microdosing.
CONCLUSION:
Our findings suggest that people microdosing are commonly doing so as a self-managed therapy for mental health, either as an alternative or adjunct to conventional treatments. This is despite psychedelics remaining prohibited substances in most jurisdictions. Recent findings from clinical trials with standard psychedelic doses for depression and anxiety suggest that a neurobiological effect beyond placebo is not unreasonable. Randomised controlled trials are needed, complemented by mixed methods social science research and the development of novel resources on microdosing harm reduction.

Lea, T., Amada, N., Jungaberle, H., Schecke, H., & Klein, M. (2020). Microdosing psychedelics: Motivations, subjective effects and harm reduction. International Journal of Drug Policy75, 102600., https://doi.org/10.1016/j.drugpo.2019.11.008
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Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects.

Abstract

Lysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and D-amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and D-amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), D-amphetamine (40 mg), and placebo in a randomized, double-blind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than D-amphetamine, and D-amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and D-amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and D-amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and D-amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with D-amphetamine. D-Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or D-amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and D-amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.
Holze, F., Vizeli, P., Müller, F., Ley, L., Duerig, R., Varghese, N., … & Liechti, M. E. (2019). Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects. Neuropsychopharmacology, 1-11., https://doi.org/10.1038/s41386-019-0569-3
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The ethics of psychedelic research in disorders of consciousness.

Abstract

This article provides an ethical analysis of psychedelic research involving disorders of consciousness patients. We apply two internationally accepted approaches for analyzing the ethics of human research, the Value-Validity Framework and Component Analysis, to a research program recently proposed by Scott and Carhart-Harris. We focus on Scott and Carhart-Harris’s proposal, but the ethical frameworks outlined are applicable to other novel research protocols in the science of consciousness.
Peterson, A., Tagliazucchi, E., & Weijer, C. (2019). The ethics of psychedelic research in disorders of consciousness. Neuroscience of Consciousness2019(1), niz013., https://doi.org/10.1093/nc/niz013
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Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada

Abstract

Introduction and Aims

A previous observational study of ayahuasca‐assisted therapy demonstrated statistically significant reductions in self‐reported problematic cocaine use among members of an Indigenous community in Canada. This paper aims to qualitatively explore the impact of ayahuasca‐assisted therapy on addiction and other substance use‐related outcomes and elucidate the lived experiences of participants.

Design and Methods

Qualitative interviews were conducted with 11 adult Indigenous participants of the ayahuasca‐assisted ‘Working with Addiction and Stress’ ceremonial retreats (June–September 2011). Semi‐structured interviews assessed experiences of participants following the retreats at 6‐month follow up. Thematic analysis of interview transcripts was conducted.

Results

Narratives revealed that the retreats helped participants identify negative thought patterns and barriers related to their addiction in ways that differed from conventional therapies. All participants reported reductions in substance use and cravings; eight participants reported complete cessation of at least one substance at follow up. Increased connectedness with self, others and nature/spirit was described as a key element associated with reduced substance use and cravings.

Discussion and Conclusions

This analysis expands upon prior quantitative results highlighting the therapeutic potential of ayahuasca‐assisted therapy and provides important contextual insights into why ayahuasca‐assisted therapy may have been beneficial for members of an Indigenous community seeking to address their problematic use of substances. Given limited efficacy of conventional treatments for resolving addiction issues, further research should investigate the role of ayahuasca and other psychedelic‐assisted therapies in enhancing connectedness and other key factors that may improve well‐being and reduce harmful substance use

Argento, E., Capler, R., Thomas, G., Lucas, P., & Tupper, K. W. (2019). Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada. Drug and alcohol review.

Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects

Abstract

Both psychedelics and meditation exert profound modulatory effects on consciousness, perception and cognition, but their combined, possibly synergistic effects on neurobiology are unknown. Accordingly, we conducted a randomized, double-blind, placebo-controlled study with 38 participants following a single administration of the psychedelic psilocybin (315 μg/kg p.o.) during a 5-day mindfulness retreat. Brain dynamics were quantified directly pre- and post-intervention by functional magnetic resonance imaging during the resting state and two meditation forms. The analysis of functional connectivity identified psilocybin-related and mental state–dependent alterations in self-referential processing regions of the default mode network (DMN). Notably, decoupling of medial prefrontal and posterior cingulate cortices, which is thought to mediate sense of self, was associated with the subjective ego dissolution effect during the psilocybin-assisted mindfulness session. The extent of ego dissolution and brain connectivity predicted positive changes in psycho-social functioning of participants 4 months later. Psilocybin, combined with meditation, facilitated neurodynamic modulations in self-referential networks, subserving the process of meditation by acting along the anterior–posterior DMN connection. The study highlights the link between altered self-experience and subsequent behavioral changes. Understanding how interventions facilitate transformative experiences may open novel therapeutic perspectives. Insights into the biology of discrete mental states foster our understanding of non-ordinary forms of human self-consciousness and their concomitant brain substrate.

Smigielski, L., Scheidegger, M., Kometer, M., & Vollenweider, F. X. (2019). Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects. NeuroImage196, 207-215., https://doi.org/10.1016/j.neuroimage.2019.04.009
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30 April - Q&A with Rick Strassman

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