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

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.