The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval
This double-blind, placebo-controlled, randomised, counterbalanced, within-subjects study (n=16) investigated the effects of psilocybin (8, 15, & 22mg/70kg) on prepulse inhibition, and found that it inhibited this startle reflex at short interstimulus intervals in a dose-dependent manner. Results indicated the impairment of attention and an inability to filter out unnecessary sensory information under the influence of psilocybin that is similar to patients with schizophrenia.
Authors
- Franz Vollenweider
- Boris Quednow
Published
Abstract
Introduction
Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT2A receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT2A receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans.
Methods
Sixteen subjects each received placebo or 115, 215, and 315 μg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR).
Results
Psilocybin dose-dependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs.
Discussion
These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.
Research Summary of 'The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval'
Introduction
Prepulse inhibition (PPI) of the acoustic startle response (ASR) is an operational measure of sensorimotor gating: a weak non-startling prepulse reduces the magnitude of a subsequent startle reflex, and this gating process is thought to limit sensory overload and support selective attention. Reductions in PPI have been observed in schizophrenia and related disorders and are widely used in translational psychopharmacology to probe neurobiological mechanisms relevant to psychosis. Animal studies have shown that serotonergic hallucinogens acting at 5-HT2A receptors (for example DOI) reliably disrupt PPI in rats, whereas a prior small human study reported an increase in PPI after psilocybin, raising questions about cross-species comparability and the relevance of hallucinogen challenge models to schizophrenia. Vollenweider and colleagues set out to clarify these discrepant findings by testing dose-dependent effects of the mixed 5-HT2A/1A agonist psilocybin on PPI in healthy volunteers. The study tested PPI across a range of interstimulus intervals (ISIs) from short (30, 60 ms) to long (120–2000 ms) to capture both pre-attentive and attention-sensitive gating, and concomitantly assessed subjective altered states (5D-ASC) and sustained attention (Frankfurt Attention Inventory, FAIR). The authors hypothesised, based on animal literature, that psilocybin would reduce PPI in humans in a dose-dependent manner.
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Study Details
- Study Typeindividual
- Journal
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- APA Citation
Vollenweider, F. X., Csomor, P. A., Knappe, B., Geyer, M. A., & Quednow, B. B. (2007). The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval. Neuropsychopharmacology, 32(9), 1876-1887. https://doi.org/10.1038/sj.npp.1301324
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