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

The authors thank Drs Dieter Vonderschmitt, Arnold von Eckardstein, and Kathrin Rentsch, Institute of Clinical Chemistry of the University of Zürich, for analysis of hormones and clinical-chemical parameters, and Martin Dobricki for assistance during the experimental part of the study. The authors especially thank Drs Stephan Ludewig, David Nichols, George Greer, and Francisco Moreno for critical comments on the manuscript. This investigation was financially supported by the Heffter Research Institute, Santa Fe, New Mexico, USA, and the Swiss Federal Office for Public Health (BAG grant no. 00.001023).

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Correspondence to Felix Hasler.

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Hasler, F., Grimberg, U., Benz, M.A. et al. Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose–effect study. Psychopharmacology 172, 145–156 (2004). https://doi.org/10.1007/s00213-003-1640-6

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Keywords

  • Psilocybin
  • Dose–effect study
  • Psycho(patho)logy
  • Neuroendocrinology
  • Cardiovascular effects
  • Altered states of consciousness