OPEN Foundation

Day: 28 September 2011

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Abstract

The serotonin-2A receptor (5-HT2AR) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT2AR or 5-HT1AR agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT2A/2CR antagonist ketanserin. A total of 16 healthy participants received placebo,ketanserin (40 mg p.o.), psilocybin (260 µg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT2AR stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT2AR system.

Quednow, B. B., Kometer, M., Geyerand, M. A., & Vollenweider, F. X. (2012). Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers. Neuropsychopharmacology, 37, 630-640. http://dx.doi.org/10.1038/npp.2011.228
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Mystical Experiences Occasioned by the Hallucinogen Psilocybin Lead to Increases in the Personality Domain of Openness

Abstract

A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality – Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.

MacLean, K. A., Johnson, M. W., & Griffiths, R. R. (2011). Mystical Experiences Occasioned by the Hallucinogen Psilocybin Lead to Increases in the Personality Domain of Openness. Journal of Psychopharmacology, 25(11), 1453-1461. http://dx.doi.org/10.1177/0269881111420188
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30 April - Q&A with Rick Strassman

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