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


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") 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.


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.


CONCLUSIONS
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.
Hasler
Felix
F
Heffter Research Center, Psychiatric University Hospital Zürich, Lenggstrasse 31, 8029 Zürich, Switzerland. fehasler@bli.unizh.ch
Grimberg
Ulrike
U
Benz
Marco A
MA
Huber
Theo
T
Vollenweider
Franz X
FX
D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D011562:Psilocybin / Q000494:pharmacology*
D011562:Psilocybin