Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review
This systematic review (s=12, 2022) finds a significant association between the mystical experience (MEQ) and psychedelic-assisted therapy (psilocybin, ketamine, ayahuasca) outcomes in ten of the 12 studies. Although promising, half of the studies were open-label and all with small sample sizes.
Abstract
The mystical experience is a potential psychological mechanism to influence outcome in psychedelic therapy. It includes features such as oceanic boundlessness, ego dissolution, and universal interconnectedness, which have been closely linked to both symptom reduction and improved quality of life. In this review, 12 studies of psychedelic therapy utilizing psilocybin, ayahuasca, or ketamine were analyzed for association between mystical experience and symptom reduction, in areas as diverse as cancer-related distress, substance use disorder, and depressive disorders to include treatment-resistant. Ten of the twelve established a significant association of correlation, mediation, and/or prediction. A majority of the studies are limited, however, by their small sample size and lack of diversity (gender, ethnic, racial, educational, and socioeconomic), common in this newly re-emerging field. Further, 6 out of 12 studies were open-label in design and therefore susceptible to bias. Future studies of this nature should consider a larger sample size with greater diversity and thus representation by use of randomized design. More in-depth exploration into the nature of mystical experience is needed, including predictors of intensity, in order to maximize its positive effects on treatment outcome benefits and minimize concomitant anxiety.
Research Summary of 'Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review'
Introduction
Psychedelic-assisted therapies are being re-examined for a range of psychiatric and addictive disorders after a long hiatus following mid-20th century research and subsequent legal restrictions. Earlier studies and contemporary trials suggest these interventions can produce antidepressant and anxiolytic effects, reduce PTSD and substance use symptoms, and relieve end-of-life distress, while appearing relatively safe and intermittent in administration compared with conventional daily pharmacotherapies. Researchers have proposed multiple mechanisms for therapeutic effects, encompassing neurobiological processes (for example, increased neural plasticity) and psychological phenomena such as emotional breakthrough, enhanced psychological flexibility, and so-called mystical experiences characterised by oceanic boundlessness (OBN), ego dissolution, feelings of unity, and transcendence of time and space. Ko and colleagues set out to systematically review clinical trials that reported both measures of mystical-type subjective experience and quantitative therapeutic outcomes, with the primary aim of assessing whether presence or intensity of mystical experience during a psychedelic dosing session is associated with symptom reduction and improvements in quality of life. The review focused on adult clinical populations treated with psilocybin, ayahuasca or ketamine and sought evidence of correlation, mediation, or prediction between mystical experience metrics (for example MEQ, 5D-ASC, HRS, HMS) and clinical endpoints across diagnostic groups including cancer-related distress, depressive disorders, and substance use disorders.
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Ko, K., Knight, G., Rucker, J. J., & Cleare, A. J. (2022). Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review. Frontiers in Psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.917199
References (39)
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Show all 39 referencesShow fewer
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Nour, M. R., Evans, J., Nutt, D. J. et al. · Frontiers in Human Neuroscience (2016)
Carhart-Harris, R. L., Bolstridge, &. M., Day, C. M. J. et al. · Psychopharmacology (2017)
Watts, R., Luoma, J. B. · Journal of Contextual Behavioral Science (2020)
Hendricks, P. S. · International Review of Psychiatry (2018)
Krupitsky, E. M., Grinenko, A. Y. · Journal of Psychoactive Drugs (1997)
Holze, F., Vizeli, P., Müller, F. et al. · Neuropsychopharmacology (2019)
Jones, G. M., Nock, M. K. · Journal of Psychopharmacology (2022)
Rothberg, R. L., Azhari, N., Haug, N. A. et al. · Journal of Psychopharmacology (2020)
Dakwar, E., Nunes, E. V., Hart, C. L. et al. · Neuropharmacology (2018)
Griffiths, R. R., Richards, W. A., Mccann, U. et al. · Journal of Psychopharmacology (2006)
Yaden, D. B., Griffiths, R. R. · ACS Pharmacology and Translational Science (2020)
Barrett, F. S., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2015)
Strassman, R. J., Qualls, C. R., Uhlenhuth, E. H. et al. · JAMA Psychiatry (1994)
Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W. · Current Drug Abuse Reviews (2015)
Liechti, M. E., Dolder, P. C., Schmid, Y. · Psychopharmacology (2016)
Sanders, J. W. · ACS Pharmacology and Translational Science (2021)
Breeksema, J. J., van Elk, M. · ACS Pharmacology and Translational Science (2021)
Jylkkä, J. · ACS Pharmacology and Translational Science (2021)
Olson, D. E. · ACS Pharmacology and Translational Science (2020)
Romeo, B., Hermand, M., Pétillion, A. et al. · Journal of Psychiatric Research (2021)
Andersen, K. A. A., Carhart-Harris, R. L., Nutt, D. J. et al. · Acta Psychiatrica Scandinavica (2020)
Agin-Liebes, G. I., Malone, T., Yalch, M. M. et al. · Journal of Psychopharmacology (2020)
Griffiths, R. R., Johnson, M. W. · Journal of Psychopharmacology (2016)
Palhano-Fontes, F., Barreto, D., Onias, H. et al. · Psychological Medicine (2018)
Bogenschutz, M. P., Forcehimes, A. A., Pommy, J. A. et al. · Journal of Psychopharmacology (2015)
Johnson, M. W., Garcia-Romeu, A., Griffiths, R. R. · The American Journal of Drug and Alcohol Abuse (2016)
Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P. et al. · Journal of Psychopharmacology (2014)
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