NCT06853912

Psilocybin With Psychological Support (Psi-PS) for Military Veterans and First Responders With Co-occurring PTSD & Alcohol Use Disorder (AUD)

A Phase 2 Single-site, Double-blind, Placebo-controlled, Randomized Clinical Trial With an Open-label Extension Phase to Examine the Safety, Subjective Experiences, Acute Effects, and Suitability of Psilocybin Combined With Psychological Support (Psi-PS) for Military Veterans and First Responders With Co-occurring Alcohol Use Disorder (AUD) and Posttraumatic Stress Disorder (PTSD)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Nathan Brashares Sackett · Academic / Other
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This study is a phase 2 single-site, double-blind, placebo-controlled, randomized clinical trial with an open-label extension phase to examine the safety of psilocybin (25 mg) combined with psychological support (Psi-PS) for treatment of approximately 40 military veterans and first responders (ages 21-65) with co-occurring alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). Psychological support is defined as providing safety, reassurance, active listening, and empathetic presence during the drug administration session in a nondirective manner. We hypothesize that Psi-PS may provide a safe treatment for participants. The primary objective of study is to characterize the safety of psilocybin combined with psychological support (Psi-PS) for individuals with co-occurring alcohol use disorder (AUD) and PTSD.

Detailed description

There is growing evidence suggesting that psychedelic drugs, when paired with therapy, may constitute a safe and effective form of treating a diverse range of psychopathological issues such as alcohol use disorder (AUD) and PTSD (Bogenschutz et al., 2015, 2022; Dakwar et al., 2020; Grabski et al., 2022; Mitchell et al., 2021, 2023). However, to date, no studies have explored any form of psychedelic-assisted therapy in the treatment of patients with co-occurring AUD and PTSD, despite high rates of comorbidity. This study will be the first of its kind to evaluate the safety of psilocybin paired with therapy to target symptoms of comorbid AUD and PTSD. Data derived from this clinical trial will help shed light on whether Psi-PS may be safe for those suffering from both PTSD and AUD. Taken together, we propose the following primary, secondary, and exploratory objectives: 1. Primary Objective: Characterize the safety of psilocybin combined with psychological support (Psi-PS) for participants during the drug administration session (DAS) while the drug's acute effects are ongoing, approximately 24 hours after the DAS when the drug's acute effects have subsided, and approximately one-week post-DAS. 2. Exploratory Objective: (1) Explore the subjective experiences of Psi-PS within approximately 24 hours following the DAS, i.e., when the drug's acute effects have subsided, approximately one-week following the DAS, and at follow-up at approximately three-months. (2) Assess acute effects of Psi-PS on a range of variables at baseline and weeks 1, 2, 4, 12, and 24 post-DAS; (3) Further, assess suitability at baseline and approximately 4-weeks post-DAS. This study is a single-site, double-blinded, placebo-controlled, randomized clinical trial with an open-label extension phase assessing safety in two conditions: 1. Psi-PS (psilocybin combined with psychological support); and 2. placebo and nondirective psychological support. The study will last approximately 26-32 weeks and is composed of two preparation sessions; one Drug Administration Session (DAS), where 25 mg of oral psilocybin (PEX010) or inert placebo (PCB2) is administered in a clinical setting with two facilitators present; and three integration sessions. Placebo conditions will receive the same psychological support but will receive an inert placebo. 4-weeks after DAS, the study will be unblinded and those who received placebo will be offered Psi-PS for the open-label extension phase, following the same procedures. The intended sample size for the study is approximately 40 military veterans and first responders (ages 21-65) with co-occurring alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). Study drug shipments will arrive on-site pre randomized by the manufacturer, and double-blinding will be maintained throughout the study by using a placebo that is designed to have similar physical characteristics as the study drug. All participants will then be followed for a total of 6 months (24 weeks) following the DAS to assess durability of potential effects.

Conditions

• Alcohol Use Disorder (AUD)
• PTSD

Interventions

Type	Name	Description
DRUG	Psilocybin 25 mg	Botanical drug product PEX010(25) contains the drug substance, PYEX, which is primarily composed of psilocybin (delivered in a capsule)
DRUG	Maltodextrin (Placebo)	25 mg of Maltodextrin (delivered in a capsule)

Timeline

• Start date: 2025-06-01
• Primary completion: 2026-06-01
• Completion: 2026-06-01
• First posted: 2025-03-03
• Last updated: 2025-08-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study