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Cited by 224Psychedelics and Drug StudiesParanormal Experiences and BeliefsPain Management and Placebo Effect

Predicting Reactions to Psychedelic Drugs: A Systematic Review of States and Traits Related to Acute Drug Effects

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Aday, Jacob S., Davis, Alan K., Mitzkovitz, Cayla M., Bloesch, Emily K., Davoli, Christopher C.·2021·ACS Pharmacology & Translational Science
DOI 10.1021/acsptsci.1c00014PMC PMC8033773
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Abstract

Psychedelic drugs are increasingly being incorporated into therapeutic contexts for the purposes of promoting mental health. However, they can also induce adverse reactions in some individuals, and it is difficult to predict before treatment who is likely to experience positive or adverse acute effects. Although consideration of setting and dosage as well as excluding individuals with psychotic predispositions has thus far led to a high degree of safety, it is imperative that researchers develop a more nuanced understanding of how to predict individual reactions. To this end, the current systematic review coalesced the results of 14 studies that included baseline states or traits predictive of the acute effects of psychedelics. Individuals high in the traits of absorption, openness, and acceptance as well as a state of surrender were more likely to have positive and mystical-type experiences, whereas those low in openness and surrender or in preoccupied, apprehensive, or confused psychological states were more likely to experience acute adverse reactions. Participant sex was not a robust predictor of drug effects, but 5-HT2AR binding potential, executive network node diversity, and rACC volume may be potential baseline biomarkers related to acute reactions. Finally, increased age and experience with psychedelics were individual differences related to generally less intense effects, indicating that users may become slightly less sensitive to the effects of the drugs after repeated usage. Although future well-powered, placebo-controlled trials directly comparing the relative importance of these predictors is needed, this review synthesizes the field’s current understanding of how to predict acute reactions to psychedelic drugs.

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Crossref · 10.1021/acsptsci.1c00014

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  • Patients who exhibit apprehension, preoccupation, or baseline attachment avoidance appear to be more likely to have challenging experiences following administration of a psychedelic drug.

    “patients who exhibit apprehension, preoccupation, or baseline attachment avoidance appear to be more likely to have challenging experiences following administration of a psychedelic drug”

    From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [281]

  • Previous research suggested a general trend toward reduced psychedelic drug effects with advancing age.

    “To our knowledge, this is the first report of a relationship between age and psychedelic-induced ego dissolution, but previous research suggested a general trend toward reduced psychedelic drug effects (Aday et al., 2021) or fewer impairments of control and cognition with advancing age (Studerus et al., 2012).”

    From Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response (2024) · cites this paper as Aday et al., 2021

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Authors
Aday, J. S., Davis, A. K., Mitzkovitz, C. M., Bloesch, E. K., & Davoli, C. C.
Affiliations
  • Central Michigan University (US)
  • Johns Hopkins University (US)
Corresponding author
Aday, Jacob S.
ORCID
Venue
ACS Pharmacology & Translational Science
Publisher
American Chemical Society (ACS)
Published
2021-03-05
Volume
4
Issue
2
Pages
424-435
ISSN
2575-9108 (ISSN-L)
DOI
10.1021/acsptsci.1c00014
PMC
PMC8033773
OpenAlex
W3134897339
Cited by
224
References
78
Citations by year
2026: 32 · 2025: 46 · 2024: 58 · 2023: 42 · 2022: 32 · 2021: 14
FWCI
4.85
Type
journal article
Language
en
Open access
Licence
Locations
  • ACS Pharmacology & Translational Science (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • the?Steven?and Alexandra Cohen Foundation
  • Blake Mycoskie
  • Craig?Nerenberg
  • Matt Mullenweg
  • Tim Ferriss
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Social Sciences › Psychology › Social Psychology › Paranormal Experiences and Beliefs
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Keywords
psychedelics, acute drug effects, adverse drug reactions, mystical experience, personality traits, absorption, openness to experience, acceptance, psychological state, surrender, executive network, biomarkers, individual differences, psychedelic experience

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