Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers
This placebo-controlled, double-blind study (n=16) investigated the effects of psilocybin (18.2mg/70kg) on sensorimotor gating, an automatic ability to filter unnecessary information, and controlled response inhibition, a deliberate ability to ignore conflicting information in healthy volunteers. Psilocybin disrupted both of these processes, and this effect was reversed by selectively blocking the serotonergic pathway with ketanserin (40mg) pretreatment.
Authors
- Franz Vollenweider
- Matthias Kometer
- Boris Quednow
Published
Abstract
Introduction
The serotonin-2A receptor (5-HT2AR) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioural 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.
Methods
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 behavioural inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test.
Results
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.
Discussion
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.
Research Summary of 'Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers'
Introduction
Automatic and controlled information-processing deficits, including impairments in early and late inhibitory gating, are considered core features of schizophrenia and have been linked to the serotonin system. Quednow and colleagues note that early automatic inhibition (sensorimotor gating) and controlled behavioural inhibition have been associated specifically with serotonin-2A receptors (5-HT2A R), and that changes at this receptor might contribute to the inhibitory deficits seen in schizophrenia. The hallucinogen psilocybin is metabolised to psilocin, which acts at multiple 5-HT receptor subtypes including 5-HT2A and 5-HT1A, and prior studies have shown that psilocybin alters prepulse inhibition (PPI) and certain measures of cognitive control in humans; however, it remained unclear which receptor actions (5-HT2A vs 5-HT1A or others) mediate these effects. This study set out to test whether the 5-HT2A/2C receptor antagonist ketanserin would attenuate psilocybin-induced deficits in automatic and controlled inhibition in healthy volunteers. Using a placebo-controlled, double-blind, randomized, counterbalanced design, the investigators examined effects on sensorimotor gating (PPI), behavioural inhibition and attentional control (a trial-by-trial Color–Word Stroop Test), and subjective altered states of consciousness (5D-ASC), comparing placebo, ketanserin, psilocybin, and psilocybin plus ketanserin conditions. The working hypothesis was that ketanserin pretreatment would reduce psilocybin-induced disruptions of PPI and Stroop interference and prevent the altered state of consciousness induced by psilocybin.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Quednow, B. B., Kometer, M., Geyer, M. A., & Vollenweider, F. X. (2012). Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers. Neuropsychopharmacology, 37(3), 630-640. https://doi.org/10.1038/npp.2011.228
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