Exposure‐Response Analysis to Assess the Concentration‐QTc Relationship of Psilocybin/Psilocin
Elyes Dahmane, Paul R. Hutson, Jogarao Gobburu
Clinical Pharmacology in Drug Development April 6, 2020 DOI: 10.1002/cpdd.796 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label single ascending dose study Peer reviewed |
|---|---|
| Intervention | Psilocybin |
| Dose | 0.3 to 0.6 mg/kg |
| Topics | Psilocybin |
| Keywords | Hallucinogen Pharmacology Qt interval Traditional medicine Anesthesia |
| Citations | 44 |
| Key points | Psilocin shows a shallow concentration-dependent QTc prolongation, with clinically meaningful effects only at concentrations above those expected with a 25 mg dose. |
Abstract
Abstract Psilocybin is being developed for treating major depressive disorder. Psilocybin is readily dephosphorylated to psilocin upon absorption. The potential for psilocin proarrhythmic effect was assessed using a concentration‐QTc interval (C‐QTc) analysis from an open‐label single ascending dose study of psilocybin. Psilocybin doses ranged from 0.3 to 0.6 mg/kg. This trial showed a significant but shallow C‐QTc relationship. At the clinical dose of 25 mg, the mean psilocin maximum concentration is 18.7 ng/mL, and the associated mean (upper 90% confidence interval of mean) QTcF change is 2.1 (6.6) milliseconds. Given the short half‐life of psilocin of about 4 hours, there would be no accumulation after monthly oral doses used in clinical trials. The upper limit of the 90% confidence interval of the model‐predicted mean ΔQTcF crossed 10 milliseconds at a psilocin concentration of 31.1 ng/mL. At a supraclinical psilocin maximum concentration of about 60 ng/mL, ΔQTcF remains low, with a mean (upper limit of the 90% confidence interval) of 9.1 (17.9) milliseconds. This analysis enabled the characterization of the C‐QTc relationship and prediction of QTc prolongation at the expected clinical and possible higher psilocybin doses.
Comparable studies
Other non-randomized and open-label trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Patients with moderate-to-severe, unipolar, treatment-resistant major depression | 2016 | Open-label feasibility trial | n = 12 |
| Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression | 2017 | Open-label trial | n = 20 |
| Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Psychiatrically healthy nicotine-dependent smokers | 2014 | Open-label pilot study | n = 15 |
| Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression | 2018 | Clinical trial | n = 20 |
| Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder Subjects with obsessive-compulsive disorder (OCD) | 2006 | Controlled clinical trial |
Citations in the library
Cited by 39
- Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double‐Blind, Placebo‐Controlled, Crossover Study in Healthy Subjects Clinical Pharmacology & Therapeutics November 7, 2021
- Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants Clinical Pharmacology & Therapeutics December 12, 2022
- Therapeutic use of psilocybin: Practical considerations for dosing and administration Frontiers in Psychiatry December 1, 2022
- Assessing the risk–benefit profile of classical psychedelics: a clinical review of second-wave psychedelic research Psychopharmacology January 13, 2022
- Adverse experiences resulting in emergency medical treatment seeking following the use of magic mushrooms Journal of Psychopharmacology April 7, 2022
and 34 more in the library
Cites 8
- The pharmacology of psilocybin Addiction Biology October 1, 2002
- Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Therapeutic Advances in Psychopharmacology March 18, 2016
- Potential Therapeutic Effects of Psilocybin. Neurotherapeutics July 1, 2017
- Psilocybin – Summary of knowledge and new perspectives European Neuropsychopharmacology December 17, 2013
- Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults Clinical Pharmacokinetics March 28, 2017
and 3 more in the library