Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study

Psilocybin, a serotonin 5-HT(2A) receptor agonist, dose-dependently altered consciousness, attention, and mood in eight healthy subjects. At medium and high doses (215 and 315 micrograms per kilogram body weight), performance on an attention test dropped by 50%, and participants reported increased emotional excitability, dreaminess, and general inactivation. Only one person experienced transient anxiety at the highest dose. Blood pressure rose modestly after the high dose, and levels of the hormones TSH, ACTH, cortisol, and prolactin increased during peak effects, with prolactin rising after both medium and high doses. No changes occurred in heart rhythm or body temperature. The authors conclude psilocybin affects core dimensions of consciousness and physiology in a dose-dependent manner and found no evidence of harm to physical health.

Study at a glance

Abstract

RationaleSerotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT(2A) agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness.ObjectiveInvestigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters.MethodsEight subjects received placebo (PL), and 45 ("very low dose, VLD"), 115 ("low dose, LD"), 215 ("medium dose, MD"), and 315 ("high dose, HD") microg/kg body weight PY. The "Altered States of Consciousness Rating Scale" (5D-ASC), the "Frankfurt Attention Inventory" (FAIR), and the "Adjective Mood Rating Scale" (AMRS) were used to assess the effects of PY on psycho(patho)logical core dimensions, attention, and mood. A 24-h electrocardiogram (EKG) was recorded and blood pressure was measured. Plasma concentrations of thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol (CORT), adrenocorticotropic hormone (ACTH), and standard clinical chemical parameters were determined.ResultsPY dose dependently increased scores of all 5D-ASC core dimensions. Only one subject reacted with transient anxiety to HD PY. Compared with PL, MD and HD PY led to a 50% reduction of performance in the FAIR test. "General inactivation", "emotional excitability", and "dreaminess" were the only domains of the AMRS showing increased scores following MD and HD PY. The mean arterial blood pressure (MAP) was moderately elevated only 60 min following administration of HD PY. Neither EKG nor body temperature was affected by any dose of PY. TSH, ACTH, and CORT plasma levels were elevated during peak effects of HD PY, whereas PRL plasma levels were increased following MD and HD PY.ConclusionPY affects core dimensions of altered states of consciousness and physiological parameters in a dose-dependent manner. Our study provided no cause for concern that PY is hazardous with respect to somatic health.