Predicting Responses to Psychedelics: A Prospective Study

Abstract

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. 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. 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 that 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. 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.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers

“…Recent clinical trials have demonstrated potent and enduring antidepressive and anxiolytic effects of classical psychedelic drugs psilocybin and LSD Carhart-Harris et al 2016;Horstmann et al 2010;Ross et al 2016;Griffiths et al 2016;Grob et al 2011). Several studies have highlighted the mystical nature of the subjective experience resulting from administration of high dose psilocybin or LSD as a mediator for the psychiatric therapeutic benefits (Russ et al 2019;Garcia-Romeu et al 2014;Roseman et al 2018;Haijen et al 2018). However, recent evidence of sustained antidepressant-like effects of psilocybin in an animal rodent model for the study of depression after only a single dose suggests that solely biological mechanisms dependent on 5-HT 2A receptor activation may effectively underlie key CNS effects observed for this class of drug (Hibicke et al 2019).…”

How does it feel to be on psilocybin? Dose-response relationships of subjective experiences in humans

“…Although psilocybin dose is the most important determinant of the acute psychedelic experience, there is considerable inter-and intra-individual variability in subjective responses to psilocybin [55][56][57][58]. To what extend responses to psilocybin varied among studies included in our main analysis is reflected in heterogeneity parameters.…”

“…In general, current mood and psychological distress prior to the psilocybin administration have been shown to contribute to the subjective experience [55,62,63]. Previous work demonstrated that the trait absorption and having clear intentions strongly correlated with all subjective experience measures [55,56]. Further, scoring high on trait extroversion was associated with increases in visionary experience [55,63,64].…”

“…Likewise, feeling well prepared, having a recreational intention and emotional reappraisal reduced the occurrence of challenging experiences [56,64] which were associated with preoccupation [57,58] and emotional excitability prior to the experience [55]. While there are indications that challenging experiences are also associated with trait neuroticism [63,66,67], other studies found no such association [55,56,64]. These factors relating to set are often not obtained in studies but potentially contributed to the variability of subjective experiences.…”

“…Nevertheless, it should be noted that studies which used linear regression models to predict the acute subjective experience reported relatively large proportions of unexplained variances in subjective responses to psilocybin [55,56]. Despite psilocybin dose being the most important determinant of subjective experiences, the influence of non-pharmacological factors should be considered when interpreting dose-response relationships.…”