Exposure‐Response Analysis to Assess the Concentration‐QTc Relationship of Psilocybin/Psilocin
Clinical Pharmacology in Drug Development April 6, 2020 Elyes Dahmane, Paul R. Hutson, Jogarao Gobburu 44 citations
Psilocybin, a compound being developed for major depressive disorder, is converted to psilocin after absorption. A single ascending dose study (0.3 to 0.6 mg/kg) found a significant but shallow relationship between psilocin concentration and QTc interval prolongation. At a clinical dose of 25 mg, the mean peak psilocin concentration is 18.7 ng/mL, associated with a mean QTcF change of 2.1 milliseconds (upper 90% confidence interval: 6.6 ms). The upper confidence limit crossed 10 ms at 31.1 ng/mL psilocin. Even at a supraclinical concentration of 60 ng/mL, the mean QTcF increase is 9.1 ms (upper limit 17.9 ms). Psilocin's short half-life (about 4 hours) suggests no accumulation with monthly oral dosing.