The effects of the preferential 5-HT2A agonist psilocybin on prepulse inhibition of startle in healthy human volunteers depend on interstimulus interval
OrthoEvidence Journal (OE Journal) - ACE Report
OE Journal. 2022;10(11):12 Neuropsychopharmacology. 2007 23-Feb;():. 10.1038/sj.npp.1301324What this means for my practice?
In addition to the reduced PPI at 30 ms ISIs and increased PPI at 120-2000 ms ISIs, psilocybin dose-dependently impaired sustained attention. Psilocybin also increased all scores on the 5D-ASC except auditory alteration. The finding that psilocybin did not affect startle reactivity is consistent with previous animal studies using other 5-HT2A/C receptor agonists such as DOI. The correlation between reduced PPI at 30 ms and sustained attention impairments reflects deficits in early pre-attentive information processing. Altogether, these findings demonstrate that 5-HT2A/5-HT1A receptor activation can affect PPI of the acoustic startle and clarify contradictory findings of effects on PPI in animals vs humans. The results are limited by the small sample size.
Study Summary
Sixteen healthy subjects underwent a double-blind, randomized placebo-controlled study to test the effects of psilocybin on the prepulse inhibition (PPI) of the startle response. Subjects randomly received a placebo and three different doses of psilocybin (115, 215 and 315 microg/kg) at four-week intervals. PPI was measured at various interstimulus intervals (ISIs) at the peak and post-peak effects of psilocybin. In a dose-dependent manner, psilocybin reduced PPI at short (30 ms) ISIs, had no effect at medium (60 ms) ISIs and increased PPI at long (120-2000 ms) ISIs. Psilocybin did not affect startle reactivity or habituations and the reduced PPI at the 30 ms ISI was positively correlated with psilocybin-induced impairments in sustained attention performance.
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