Prediction of Psilocybin Response in Healthy Volunteers

Abstract

Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

A placebo-controlled investigation of synaesthesia-like experiences under LSD

“…Although they should be interpreted with caution, these correlations are potentially consistent with previous research showing that absorption predicts the occurrence of LSD-induced synaesthesia-like experiences (Studerus et al, 2012) and evidence indicating that synaesthetes score higher on psychometric measures of absorption (Chun & Hupe, 2015;Glicksohn, Steinbach, & ElimalachMalmilyan, 1999;Rader & Tellegen, 1987) and the related trait of openness to experience (Banissy et al, 2013). However, the present results imply that individuals exhibiting high absorption who experience LSD-induced colours will exhibit reduced stimulus-colour consistency.…”

“…Complicating matters further is that we observed heterogeneity in response to LSD with some participants exhibiting pronounced effects and others displaying only minimal responses. We provide some preliminary evidence that these effects are moderated by proneness to states of absorption, in line with previous research (Studerus et al, 2012).…”

“…Data were analyzed with 2 (Condition: placebo v. LSD) × 2 (Task: grapheme v. sound) repeated measures ANOVAs. Data were further analyzed using 2 × 2 ANCOVAs with the same factors and including self-report measures (see above) as continuous covariates in order to follow-up on previous research suggesting that such variables may moderate drug-induced synaesthesia (Studerus et al, 2012).…”

“…Toward this end, as part of a larger placebo-controlled validation study of the feasibility of studying LSD in a neuroimaging environment (Carhart-Harris et al, 2015), participants rated the vividness of colour experiences and selected specific colours in response to a set of graphemes and sounds in LSD and placebo conditions. Participants also independently completed measures of absorption and visual imagery (Blajenkova, Kozhevnikov, & Motes, 2006;Jamieson, 2005;Ott, 2007;Tellegen & Atkinson, 1974), which may be related to the experience of drug-induced synaesthesia-like experiences (Studerus, Gamma, Kometer, & Vollenweider, 2012). We expected that LSD would produce synaesthesia-like experiences, particularly for sound stimuli, to a greater degree than placebo.…”

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

“…Oxytocin is thought to contribute to the empathogenic and prosocial effects of MDMA (60) The primary safety concerns with hallucinogen research are psychological rather than somatic adverse effects (1). In laboratory studies that use psilocybin, ketamine, or MDMA, moderate anticipatory anxiety is common at the beginning of the onset of the drug's effects (58,64,65). Acute anxiety was also infrequently reported when LSD was administered at the same dose as the one used in the present study for LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases (11).…”