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

People who are more open, accepting, and prone to absorption, as well as those who enter a psychedelic session with a mindset of surrender, are more likely to have positive, mystical-type experiences. Conversely, individuals who are low in openness or surrender, or who arrive in a preoccupied, apprehensive, or confused state, are more likely to experience adverse reactions. A systematic review of 14 studies found that sex is not a robust predictor of drug effects, but certain brain-based measures—such as 5-HT2AR binding potential, executive network node diversity, and rACC volume—may serve as biomarkers. Older age and prior experience with psychedelics are linked to less intense effects, suggesting users may become slightly less sensitive after repeated use.

Study at a glance

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.