Set & SettingPersonality & Trait Factors

Predicting responses to psychedelics: a prospective study

This longitudinal survey study (n=654 > 535 > 379 > 315 > 212, with increasing dropout) gathered data from individuals at five different time points before and after they undertook a preregistered psychedelic experience, and assessed variables related to personality traits, intentions, and the set and setting to predict the acute effects of taking the psychedelic, as well as long-term outcomes of subjective well-being. Baseline trait variables, such as absorption, strongly influenced long-term well-being. However, acute variables such as the intention and intensity of having mystical experiences also positively influenced well-being up to four weeks after the psychedelic experience.

Authors

  • Robin Carhart-Harris
  • David Nutt
  • Christopher Timmermann

Published

Frontiers in Pharmacology
individual Study

Abstract

Introduction

Responses to psychedelics are notoriously difficult to predict, yet significant work is currently underway to assess their therapeutic potential and the level of interest in psychedelics among the general public appears to be increasing. We aimed to collect prospective data in order to improve our ability to predict acute- and longer-term responses to psychedelics.

Methods

Individuals who planned to take a psychedelic through their own initiative participated in an online survey (www.psychedelicsurvey.com). Traits and variables relating to set, setting and the acute psychedelic experience were measured at five different time points before and after the experience. Principle component and regression methods were used to analyse the data. Sample sizes for the five time points were N = 654, N = 535, N = 379, N = 315, and N = 212 respectively.

Results

Psychological well-being was increased 2 weeks after a psychedelic experience and remained at this level after 4 weeks. Higher ratings of a “mystical-type experience” had a positive effect on the change in well-being after a psychedelic experience, whereas the other acute psychedelic experience measures, i.e., “challenging experience” and “visual effects”, did not influence the change in well-being after the psychedelic experience. Having “clear intentions” for the experience was conducive to mystical-type experiences. Having a positive “set” as well as having the experience with intentions related to “recreation” were both found to decrease the likelihood of having a challenging experience. The baseline trait “absorption” and higher drug doses promoted all aspects of the acute experience, i.e., mystical-type and challenging experiences, as well as visual effects. When comparing the relative contribution of different types of variables in explaining the variance in the change in well-being, it seemed those baseline trait variables had the strongest effect on the change in well-being after a psychedelic experience. These results confirm the importance of extra-pharmacological factors in determining responses to a psychedelic.

Discussion

We view this study as an early step towards the development of empirical guidelines that can evolve and improve iteratively with the ultimate purpose of guiding crucial clinical decisions about whether, when, where and how to dose with a psychedelic, thus helping to mitigate risks while maximizing potential benefits in an evidence-based manner.

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Research Summary of 'Predicting responses to psychedelics: a prospective study'

Introduction

Haijen and colleagues situate this study within the recent resurgence of clinical and experimental work on serotonergic psychedelics, noting that single-dose administrations (notably of psilocybin) have been reported to produce enduring improvements in psychological well-being and promising clinical effects across diverse disorders. They point out that, despite accumulating evidence of therapeutic potential, the ability to predict individual acute and longer-term responses to psychedelics remains limited. Prior work has linked acute ‘‘mystical’’ or ‘‘peak’’ experiences and trait absorption to favourable outcomes and identified some predictors of challenging experiences, but most existing studies are limited either to controlled settings (often with psilocybin only) or to prediction of acute effects rather than longer-term change. This paper therefore set out to collect prospective, naturalistic data to improve prediction of both the acute psychedelic experience and subsequent changes in psychological well-being. Using an online, longitudinal survey administered at five time points (1 week before, 1 day before, 1 day after, 2 weeks after and 4 weeks after a planned psychedelic experience), the investigators aimed to test two primary hypotheses: that subjective well-being (measured by the WEMWBS) would increase at 2 weeks post‑experience, and that features of the acute experience—particularly mystical-type experiences—would predict later changes in well-being. They also planned to examine the relative contributions of baseline trait variables, ‘‘set’’ and ‘‘setting’’ factors, intentions for the experience, and drug dose to acute and longer-term outcomes.

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Dose-response relationships of psilocybin-induced subjective experiences in humans

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Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings

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Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing

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Development of the Psychological Insight Questionnaire among a sample of people who have consumed psilocybin or LSD

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108 cited
The History of Psychedelics in Psychiatry

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The potential synergistic effects between psychedelic administration and nature contact for the improvement of mental health

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Pivotal Mental States

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Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies

Andersen, K. A. A., Carhart-Harris, R. L., Nutt, D. J. et al. · Acta Psychiatrica Scandinavica (2020)

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

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82 cited
Mystical Experiences in Retrospective Reports of First Times Using a Psychedelic in Finland

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Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments

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Compassionate use of psychedelics

Greif, A., Šurkala, M. · Medicine Health Care and Philosophy (2020)

Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance

Wolff, M., Evens, R., Mertens, L. J. et al. · Frontiers in Psychiatry (2020)

Acute effects of psilocybin on glutamate concentration levels, functional connectivity and subjective state

Mason, N. L., Feilding, A., Ramaekers, J. G. · European Neuropsychopharmacology (2020)

Reported effects of psychedelic use on those with low well-being given various emotional contexts

Mason, N. L., Dolder, P. C., Kuypers, K. P. C. · Drug Science Policy and Law (2020)

12 cited
Therapeutic Use of LSD in Psychiatry: A Systematic Review of Randomized-Controlled Clinical Trials

Fuentes, J. J., Fonseca, F., Elices, M. et al. · Frontiers in Psychiatry (2020)

From Egoism to Ecoism: Psychedelics Increase Nature Relatedness in a State-Mediated and Context-Dependent Manner

Kettner, H., Gandy, S., Haijen, E. C. H. M. et al. · International Journal of Environmental Research and Public Health (2019)

131 cited
Emotional breakthrough and psychedelics: validation of the emotional breakthrough inventory

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REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)

Replication and extension of a model predicting response to psilocybin

Russ, S. L., Carhart-Harris, R. L., Maruyama, G. et al. · Psychopharmacology (2019)

55 cited
How do psychedelics work?

Carhart-Harris, R. L. · Current Opinion in Psychiatry (2019)

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