Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose–effect study
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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.
Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters.
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.
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.
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.
KeywordsPsilocybin Dose–effect study Psycho(patho)logy Neuroendocrinology Cardiovascular effects Altered states of consciousness
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).
- Cuomo MJ, Dyment PG, Gammino VM (1994) Increasing use of ‘ecstasy’ (MDMA) and other hallucinogens on a college campus. Am College Health 42:271–274Google Scholar
- Derogatis LR, Lipman RS, Covi L (1973) SCL-90: an outpatient psychiatric rating scale—preliminary report. Psychopharm Bull 9:13–28Google Scholar
- Dittrich A (1993) Psychological aspects of altered states of consciousness of the LSD type: measurement of their basic dimensions and prediction of individual differences. In: Pletscher A, Ladewig D (eds) Fifty years of LSD. Current status and perspectives of hallucinogens. Parthenon, New York, pp 101–118Google Scholar
- Dittrich A (1996) Ätiologie-unabhängige Strukturen veränderter Wachbewusstseinszustände. VWB Verlag, BerlinGoogle Scholar
- Dittrich A (1998) The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychology 31:80–84Google Scholar
- Dittrich A, Lamparter D, Maurer M (1999) 5D-ABZ: Fragebogen zur Erfassung Aussergewöhnlicher Bewusstseinszustände. Eine kurze Einführung. PSIN Plus, ZürichGoogle Scholar
- Fahrenberg J, Hampel R, Selg H (1984) Das Freiburger Persönlichkeitsinventar FPI. D-Göttingen, HogrefeGoogle Scholar
- Fried R (2000) Aspartatamino-transferase (AST, ASAT, GOT) im Plasma. Manual of the Institute of Clinical Chemistry of the University Hospital of Zürich. ZürichGoogle Scholar
- Gouzoulis-Mayfrank E, Thelen B, Habermeyer E, Kunert HJ, Kovar KA, Lindenblatt H, Hermle L, Spitzer M, Sass H (1999) Psychopathological, neuroendocrine and autonomic effects of 3,4-methlyenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers. Results of an experimental double-blind placebo-controlled study. Psychopharmacology 142:41–50PubMedGoogle Scholar
- Hasler F (1997) Untersuchungen zur Humanpharmakokinetik von Psilocybin. Thesis, University of BernGoogle Scholar
- Isbell H (1959) Comparison of reactions induced by psilocybin and LSD-25 in man. Psychopharmacology 1:29–38Google Scholar
- Janke W, Debus G (1978) Die Eigenschaftswörterliste (EWL-K)—Ein Verfahren zur Erfassung der Befindlichkeit. Hogrefe, GöttingenGoogle Scholar
- Laux L, Glanzmann P, Schaffner P, Spielberger CD (1981) Das State-Trait-Angstinventar (STAI). Beltz, WeinheimGoogle Scholar
- Lindenblatt H, Kraemer E, Holzmann-Erens P, Gouzoulis-Mayfrank E, Kovar KA (1998) Quantitation of psilocin in human plasma by high-performance liquid chromatography and electrochemical detection: comparison of liquid–liquid extraction with automated on-line solid-phase extraction. J Chromatogr B 709:255–263CrossRefGoogle Scholar
- Lohrer F, Albers M (1999) Biological drugs—is there a change in substance abuse? Psychiatr Prax 26:199–201Google Scholar
- Meltzer HY, Nash JF (1988) Serotonin and mood: neuroendocrine aspects. In: Ganten D, Pfaff D (eds) Neuroendocrinology of mood. Springer, Berlin Heidelberg New York, pp 183–210Google Scholar
- Meneses A (1998) Physiological, pathophysiological and therapeutic roles of 5-HT systems in learning and memory. Rev Neurosci 4:275–289Google Scholar
- Moosbrugger H, Oehlschlägel J (1996) FAIR Frankfurter Aufmerksamkeitsinventar. Testmanual, Hans Huber, GöttingenGoogle Scholar
- O’Malley BP, Jennings PE, Cook N, Barnett DB, Rosenthal FD (1984) The role of serotonin (5-HT) in the control of TSH and prolactin release in euthyroid subjects assessed by the administration of ketanserin (5-HT2 antagonist) and zimelidine (5-HT re-uptake inhibitor). Psychoneuroendocrinology 9:13–19CrossRefPubMedGoogle Scholar
- Prescott RW, Kendall-Taylor P, Weightman DR, Watson MJ, Ratcliffe WA (1984) The effect of ketanserin, a specific serotonin antagonist on the PRL, HG, ACTH and cortisol response to hypoglycaemia in normal subjects. Clin Endocrinol 20:137–142Google Scholar
- Vollenweider FX, Leenders KL, Scharfetter C, Maguire P, Stadelmann O, Angst J (1997) Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis. Neuropsychopharmacology 16:357–372Google Scholar
- Vollenweider FX, Vontobel P, Hell D, Leenders KL (1999) 5-HT modulation of dopamine release in basal ganglia in psilocybin-induced psychosis in man—a PET study with (11C)raclopride. Neuropsychopharmacology 20:424–433Google Scholar
- Wittchen HU, Pfister H (1997) DIA-X-Interview. Swet Test Services, FrankfurtGoogle Scholar