This double-blind, placebo-controlled, within-subjects study investigated various dosages of psilocybin (placebo – 22mg/70kg) and found dose-dependent increases in altered states of consciousness (5D-ASC) and physiological measures (but only small and transient effects).

Abstract of Acute psychological and physiological effects of psilocybin in healthy humans

“Rationale Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT2A agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness.

Objective Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters.

Methods Eight subjects received placebo (PL), and 45 (“very low dose, VLD”), 115 (“low dose, LD”), 215 (“medium dose, MD”), and 315 (“high dose, HD”) μg/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.

Results PY 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.

Conclusion PY 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.”

Authors: Felix Hasler, Ulrike Grimberg, Marco A. Benz, Theo Huber & Franz X. Vollenweider

Summary of Acute psychological and physiological effects of psilocybin in healthy humans

Psilocybin, the main psychoactive principle of hallucinogenic mushrooms, interacts mainly with serotonergic neurotransmission (5-HTj, 5-HT2, and 5-HT2 receptor subtypes) and has no affinity for dopamine D2 receptors. However, some of the psychotropic effects of PY might be due to downstream effects on other neurotransmitter systems. Psilocin, a metabolite of PY, can be used as an experimental tool in neurosciences to study the neurobiological basis of altered states of consciousness. Its pharmacological and toxicological properties in humans must be closely investigated.

Two human studies on the acute somatic effects of PY from 1959 and 1961, and one study published in 1999 by Gouzoulis-Mayfrank et al., found no significant response of cortisol, prolactin, or growth hormone on administration of a single moderate dose of PY.

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Find this paper

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

https://doi.org/10.1007/s00213-003-1640-6

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Cite this paper (APA)

Hasler, F., Grimberg, U., Benz, M. A., Huber, T., & Vollenweider, F. X. (2004). Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose–effect study. Psychopharmacology, 172, 145-156.

Study details

Compounds studied
Psilocybin Placebo

Topics studied
Healthy Subjects Safety

Study characteristics
Original Placebo-Controlled Double-Blind Within-Subject

Participants
8 Humans

Institutes

Institutes associated with this publication

University of Zurich
Within the Department of Psychiatry, Psychotherapy and Psychosomatics at the University of Zurich, Dr Mialn Scheidegger is leading team conducting psychedelic research and therapy development.

Compound Details

The psychedelics given at which dose and how many times

Psilocybin 8 - 22
mg | 5x