Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies

Abstract

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

Psychiatry & the psychedelic drugs. Past, present & future

“…A serious adverse event is defined as a reaction that results in death, is life threatening, results in prolonged hospitalisation or persistent or significant disability. The absence of this so far is consistent with research using psilocybin in healthy volunteers (Studerus et al, 2011), pre-prohibition research with LSD and mescaline (Cohen, 1960), modern population level data on recreational use of psilocybin mushrooms and other psychedelics Hendricks et al, 2014Hendricks et al, , 2015Johansen and Krebs, 2015;Krebs and Johansen, 2013a;Nutt et al, 2010;Walsh et al, 2016) and toxicology work (Gable, 2004). However, modern trials with psilocybin are notable for not collecting adverse event data systematically in a manner that allows aggregated analyses.…”

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

“…1) produce hallucinogenic effects with relative low potency in man (Repke et al, 1985). Psilocin is orally psychoactive above 5-10 mg, and DMT is active at parenteral doses of 20-100 mg (Araujo et al, 2015;Shulgin and Shulgin, 1997;Studerus et al, 2011;Tittarelli et al, 2015). In contrast, a 5-methoxy group, such as in 5-MeO-AMT ( Fig.…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…Similarly, although these substances are used frequently by humans, addiction appears to be very uncommon, and indeed they have been used to treat alcohol addiction (Gable, 1993;Studerus et al, 2011;van Amsterdam et al, 2011;Krebs and Johansen, 2013). This is consistent with the rather low-affinity, mixed and delayed efficacy of LSD on various types of DA receptors (Passie et al, 2008); with a very low affinity of psilocybin/psilocin to DA receptors (Passie et al, 2002) and with salvinorin A having selective high affinity to and agonistic efficacy on k-opioid receptors (Roth et al, 2002;Chavkin et al, 2004).…”

“…Persistent effects such as perception disorders have also been observed in healthy individuals after experimentally administered doses of psilocybin (Studerus et al, 2011), and these could all be managed by interpersonal discussion and support. Furthermore, drug-free visual experiences were observed in 62% of the respondents in a webbased study that analyzed a population of 2455 participants for abnormal experiences associated with a history of hallucinogen use, especially LSD (Baggott et al, 2011).…”