The Promise of Therapeutic Psilocybin: An Evaluation of the 134 Clinical Trials, 54 Potential Indications, and 0 Marketing Approvals on ClinicalTrials.gov

Summary & key facts

The authors reviewed 134 clinical trials of psilocybin listed on ClinicalTrials.gov and found many small, often unblinded, single-site studies that take years to finish and rarely post results. Only three trials have reached advanced phases recently, and there are no FDA marketing approvals for psilocybin. The paper concludes that the field needs better, sequentially planned and well-funded trials with proper blinding and multicenter expertise to show whether psilocybin can meet regulatory standards.

Key facts:

• The review analyzed 134 trials that specifically listed psilocybin as an intervention on ClinicalTrials.gov.
• Many trials were small and often unblinded, commonly enrolling about 10–20 participants per study.
• Only three advanced trials were submitted (1 Phase 2/3 and 2 Phase 3), and these appeared only in the last two years.
• Of the 134 trials, 28 (20.9%) were marked complete, and only 9 of those 28 (32.1%) had posted results.
• The average reported time to complete a trial was 1,217 ± 345 days (about 3.3 years); the shortest completed trial lasted 254 days and the longest 3,532 days.
• A large recent surge occurred: 102 trials were started in the last five years (including proposed 2024 starts).
• The trials targeted 54 different conditions; 27 were healthy volunteer studies, major depressive disorder (MDD) appeared in 17 trials, treatment-resistant depression (TRD) in 16, and combined depression categories total 39 trials. Substance
• The authors report that psilocybin is not FDA-approved for marketing (no Phase 4 trials listed), though the FDA granted breakthrough therapy designation for psilocybin in 2018 for TRD and in 2019 for MDD.

Abstract

The hundreds of psilocybin clinical trials initiated over the past twenty years comprising a myriad of potential indications may actually be slowing this potential game-changing mental health therapeutic agent's approval and is costing excessive amounts of capital. To fully evaluate the actual potential of psilocybin, purposeful clinical trials need to be designed well, executed efficiently, and analyzed utilizing sequential and statistically valid processes for each potential indication. This will require a change from the current exploratory forays to defined, well-funded, sequential pharmaceutical development practices, including adequate and appropriate blinding of studies, statistical design to determine the number of participants and more importantly, professional expertise in conducting multicenter trials. Unfortunately, these results demonstrate little real progress towards FDA approval of psilocybin and a field with no clear direction forward.

Topics

Chemical synthesis and alkaloids Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Blinding Clinical trial Hallucinogen Internal medicine Medicine Pharmacology Psilocybin