Anxiety DisordersHealthy VolunteersPsilocybin

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

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).

Authors

  • Franz Vollenweider
  • Felix Hasler

Published

Psychopharmacology
individual Study

Abstract

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.

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

Introduction

Psilocybin (PY, 4-phosphoryloxy-N,N-dimethyltryptamine) is the principal psychoactive constituent of certain hallucinogenic mushrooms and acts primarily at serotonergic receptors, notably 5-HT2A, with additional affinity at 5-HT1A and 5-HT2C subtypes. Previous human and animal work has implicated 5-HT2A activation in alterations of perception, mood and cognition, and suggested downstream interactions with other neurotransmitter systems such as dopamine. Although a small number of human studies have examined somatic effects after single doses, the dose–response relationships of psilocybin across psychological (including altered states of consciousness and attention) and physiological domains had not been characterised comprehensively in a controlled within-subject design. Hasler and colleagues therefore set out to map acute, dose-dependent psychological and physiological effects of psilocybin in healthy volunteers and to assess its short-term somatic safety. The study aimed to measure subjective experience (using a multi-dimensional altered-states scale), mood, sustained attention, cardiac electrophysiology, cardiovascular and thermoregulatory responses, endocrine markers and standard clinical chemistry across four ascending doses plus placebo, thereby informing both mechanistic inquiry and safety considerations for human challenge studies.

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Study Details

References (2)

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