Tolerability, assessment, and prediction of psilocybin-induced altered states of consciousness

Psilocybin, a hallucinogenic drug, is generally well tolerated when administered in a controlled clinical or research setting. In pooled data from eight double-blind placebo-controlled studies involving 110 healthy subjects who received 1-4 oral doses (45-315 μg/kg), most described the experience as pleasurable, enriching, and non-threatening. Strong anxiety or dysphoria occurred only at the two highest doses in a small proportion of subjects, resolving with emotional support alone. Mild complaints 24 hours after intake included headache and fatigue. Follow-up interviews 8-16 months later found no flashbacks, prolonged psychosis, or subsequent drug abuse among any subjects.

Study at a glance

Abstract

Since the early 1990s, hallucinogenic drugs, such as psilocybin, have been increasingly used to investigate the neuronal basis of altered states of consciousness and psychosis. Furthermore, renewed interest has emerged in using these drugs as an adjunct to psychotherapy. Nevertheless, the therapeutic and experimental use of these substances is still controversial due to fears of potential harm. Although the experience of many investigators suggests that potential risks are minimal when these drugs are administered in a carefully monitored clinical or research environment, the subjective tolerability of these drugs under these conditions has not yet been evaluated in large samples. The revival of hallucinogen research during the past 20 years has also greatly increased the need for well-validated instruments assessing the the acute subjective effects of these drugs. Although Adolf Dittrich’s questionnaires for the assessment of altered states of consciousness (ASCs) were frequently used for this purpose, especially in Europe, the factorial structure of these questionnaires is not clearly established because previous psychometric investigations have serious methodological limitations. Finally, the effects of hallucinogens are believed to be critically dependent on non-pharmacological variables (e.g., the user’s personality, current mood state and environment), but few empirical studies have investigated several of these predictor variables at a time. Thus, little is known about the order of importance of these variables. To solve these problems, three empirical studies were conducted, all of which were based on pooled data from Prof. Vollenweider’s research group at the University Hospital of Psychiatry in Zurich. Vollenweider’s group was one on the first to restart human hallucinogen research in the early 1990s and since then has collected an amount of data that is unrivaled in the world. In the first study, acute, subacute, and long-term subjective effects of psilocybin were investigated by analyzing the pooled data of eight double-blind placebo-controlled experimental studies. The sample included 110 healthy subjects who had received 1-4 oral doses of psilocybin in a dose range of 45-315 μg/kg body weight. It was found that the effects of psilocybin were generally well tolerated. Most subjects described the experience as pleasurable, enriching, and non-threatening. Strong anxiety and/or dysphoria occurred only in the two highest dose conditions in a relatively small proportion of subjects and in all cases resolved by providing emotional support and without pharmacological intervention. Complaints 24 h after drug intake were mild and mostly included headache and fatigue. Furthermore, follow-up interviews conducted 8-16 months after the psilocybin sessions indicated that all of the subjects were healthy and that none of them had experienced any of the most feared negative consequences of hallucinogen exposure, that is, flashbacks, prolonged psychosis, or subsequent drug abuse.