Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function

Johnson, Matthew W.; Hendricks, Peter S.; Barrett, Frederick S.; Griffiths, Roland R.

doi:10.1016/j.pharmthera.2018.11.010

Cited by 367 publications

(357 citation statements)

References 194 publications

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“…Here, we extended these findings by revealing that the whole-brain effects of LSD can be conceptualized as a contraction or levelling of the brain's macroscale functional hierarchy -directly in line with a recently proposed unified model of psychedelic brain action (Carhart-Harris & Friston, 2019). Future work is needed to ascertain whether reductions in cortical hierarchy in the acute psychedelic experience relate to findings of rapid and sustained positive changes in relevant mental health parameters observed via psychotherapeutically-mediated experiences with these drugs (Barrett, Doss, Sepeda, Pekar, & Griffiths, 2020;Carhart-Harris, Bolstridge, et al, 2016;Griffiths et al, 2016;Johnson et al, 2019;Ross et al, 2016).…”

Section: Discussionmentioning

confidence: 89%

“…Interestingly, the mPFC/ACC is strongly implicated in self-referential processing as well as mentalizing about others (D'Argembeau et al, 2007;Dixon, Thiruchselvam, Todd, & Christoff, 2017). This association between hierarchical position and ego-dissolution is particularly noteworthy given past findings that ego-dissolution and related mystical-type phenomena are key mediators of positive outcomes in psychedelic treatment paradigms (Belser et al, 2017;Johnson et al, 2019;Roseman, Nutt, & Carhart-Harris, 2018;Watts, Day, Krzanowski, Nutt, & Carhart-Harris, 2017).…”

Section: Discussionmentioning

confidence: 92%

“…LSD is a potent psychedelic compound that elicits a wide variety of subjective effects via 5-HT2A receptor agonism and has been shown to have significant potential in the treatment of mental health conditions (Gasser et al, 2014;Johnson et al, 2019;Krebs & Johansen, 2012). Past investigations into the neural underpinnings of the LSD state revealed a number of spatially distributed changes in functional organization and dynamics, collectively suggestive of a more globally-integrated and 'entropic' mode of neural processing (Carhart-Harris, 2018;Carhart-Harris, Muthukumaraswamy, et al, 2016;Lebedev et al, 2016;Schartner et al, 2017;Tagliazucchi et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Recent years have seen a resurgence of scientific interest in lysergic acid diethylamide (LSD) and related serotonergic psychedelic compounds such as psilocybin (the active compound in 'magic mushrooms') and DMT/ayahuasca (Johnson, Hendricks, Barrett, & Griffiths, 2019;Nichols, 2016). This interest has been motivated by preliminary clinical trials suggesting their effectiveness in the treatment of multiple mental health conditions (Carhart-Harris, Bolstridge, et al, 2016;Gasser, Kirchner, & Passie, 2014;Griffiths et al, 2016;Johnson et al, 2019;Krebs & Johansen, 2012). While mechanisms underlying the potential effectiveness of psychedelic therapy remain poorly understood, investigating alterations in brain function related to the acute psychedelic state may provide relevant insights.…”

Section: Introductionmentioning

confidence: 99%

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Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex

Girn

Roseman

Bernhardt

et al. 2020

Preprint

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LSD is a potent serotonergic psychedelic compound. Findings indicate that psychotherapeutic applications of LSD and related psychedelic compounds have value in the treatment of mental health disorders. Deepening our understanding of LSD brain action may shed light on the mechanisms underlying the effectiveness of psychedelic therapy. A recent model hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested. Here, we applied an unsupervised manifold learning technique that is sensitive to cortical hierarchy to pharmacological resting-state fMRI data to assess cortical organization in the LSD state. Results directly supported our primary hypothesis: The Principal Gradient, describing a hierarchical transition from unimodal to transmodal cortex, was significantly contracted under LSD relative to placebo. Between-condition contrasts revealed that this was primarily driven by a reduction of functional differentiation at both hierarchical extremes -default and frontoparietal networks at the upper end, and somatomotor cortex at the lower. In addition, results pertaining to the visual-somatomotor Second Gradient revealed that LSD reduced the differentiation of visual from auditory/somatomotor and association regions. Significantly, gradient changes tracked state-specific changes in specific dimensions of self-reported LSD experience. These findings support a recent mechanistic model of the psychedelic state that has relevance to therapeutic applications of psychedelics. More fundamentally, these findings provide the first evidence that cortical hierarchical organization can be modulated in a state-dependent manner, highlighting an important relationship between the features of neural topography and ongoing conscious experience.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex

Girn

Roseman

Bernhardt

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Even though the recreational use of psilocybin is widespread and psilocybin has found its applications in basic research as well as in clinical studies exploring therapeutic potentials [6][7][8], so far no doseresponse relationships have been reported with regards to the psychoactive properties. Multiple reasons play a role in this.…”

Section: Introductionmentioning

confidence: 99%

How does it feel to be on psilocybin? Dose-response relationships of subjective experiences in humans

Hirschfeld

Schmidt

2020

Preprint

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Psilocybin is the active component of magic mushrooms and is well known for its psychoactive properties. Different questionnaires have been developed to systematically quantify altered states of consciousness induced by psychoactive drugs. The aim of this study was to obtain the dose-response relationships of the subjective experiences induced by psilocybin in healthy study participants. For this purpose, we applied a linear meta-regression approach on questionnaire ratings after oral administration of psilocybin in a controlled setting. Data was obtained from The Altered States Database, which contains psychometric data extracted from peer-reviewed articles published in MEDLINE-listed journals that used standardized and validated questionnaires. Our meta-analysis included data of the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire (MEQ30), and the Hallucinogen Rating Scale (HRS). We used the Robust Variance Estimation Framework to obtain linear dose-response relationship estimates for each dimension of the given questionnaires. Ratings on most dimensions and subscales of the included questionnaires correlated positively with dose. Since subjective experiences are not only determined by dose, but also by individual differences and environmental factors, our results do not necessarily generalize to recreational use, as our analyses are based on data from controlled laboratory experiments. The paper at hand could serve as a general literature citation for the use of psilocybin in experimental and clinical research, especially for the comparison of expected and observed subjective drug experiences.

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Disruptive Psychopharmacology

Heifets

Malenka

2019

JAMA Psychiatry

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Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function

Cited by 367 publications

References 194 publications

Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex

Serotonergic psychedelic drugs LSD and psilocybin reduce the hierarchical differentiation of unimodal and transmodal cortex

How does it feel to be on psilocybin? Dose-response relationships of subjective experiences in humans

Disruptive Psychopharmacology

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