Mindfulness-assisted Psychedelic Therapy

Phase 2

Recruiting

• Conditions: Mental Health
• Interventions: Drug: Psilocybin plus mindfulness training; Drug: Psilocybin

• Registration Number: NCT06233344
• Lead Sponsor: University of Southern California

Brief Summary

The goal of this clinical trial is to test psilocybin in combination with mindfulness training in healthy adults. The main question it aims to answer is "Does mindfulness training enhance the effects of psychedelic therapy (psilocybin) on mental health?" Interested individuals will complete an initial eligibility session and eligible participants will then be randomized into one of two groups: one dose of psilocybin (administered under the supervision of study therapists) combined with 8 weeks of weekly mindfulness training classes (Arm 1) or psilocybin alone (Arm 2). Both groups will complete baseline and post-treatment assessment sessions where they will complete questionnaires, computerized cognitive tests, and have an EEG (a measure of electrical activity in the brain). Both groups will also complete 2 follow-up surveys (at 8 weeks and 1 year after the post-treatment assessment) either online through REDCap or by phone or video call with a research assistant.

Detailed Description

Psilocybin is a psychoactive compound found in a variety of mushrooms that has been used for centuries to facilitate spiritual experiences. Recent evidence suggests that the combination of psilocybin with mindfulness training may enhance the therapeutic effects of these interventions for mental health; however, to date, only few studies have investigated a combination approach, and no studies have yet investigated the effects of psilocybin in combination with a formal mindfulness training program in participants with little or no prior meditation experience. We propose here to conduct a pilot study to evaluate the efficacy of psilocybin administration in combination with 8 weeks of mindfulness training. Participants (N = 40) will complete an initial eligibility session and eligible participants will then be randomized into one of two groups: psilocybin integrated with mindfulness training (MT) (Arm 1) and psilocybin alone (Arm 2). Both groups will complete baseline and post-treatment assessment sessions where they will complete questionnaires and cognitive assessments. Both groups will also complete 2 brief follow-up surveys (at 8 weeks and 1 year after the post-treatment assessment) either online through REDCap or by phone or video call with a research assistant. The primary feasibility outcome will be retention rate at the 8-week follow-up time point (percent of eligible enrolled participants who complete the 8-week follow-up). Secondary efficacy outcomes include change in psychological and mood measures, blood inflammatory \& neurotrophic markers and neurocognitive measures (EEG outcomes) from baseline to post-treatment. Safety outcomes will include the number of participants reporting adverse events and the mean severity of events. Logistic regression models will be used to examine the relationships between intervention group and the primary and secondary outcome variables. The results of this pilot study will be used to support a larger NIH and other external grant application as well as the extension of this intervention to clinical populations.

Study Timeline

• Study First Submitted: 2023-12-19
• Study First Submitted QC: 2024-01-22
• Study First Posted: 2024-01-31
• Study Start: 2025-07-30
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-22
• Last Update Posted: 2025-09-26
• Primary Completion: 2026-08
• Study Completion: 2027-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mindfulness-assisted psilocybin therapy	Psilocybin plus mindfulness training	8 weeks of mindfulness training plus one 25mg dose of psilocybin
Psilocybin only	Psilocybin	One 25mg dose of psilocybin

Primary Outcome Measures

Name	Time	Method
Retention at 8-week follow-up	8-week follow-up	The primary feasibility outcome will be participant retention (percent of eligible enrolled participants who complete the 8-week follow-up session)
Change in stress symptoms	8-week follow-up	The primary efficacy outcome will be the Short Perceived Stress Scale. This 10-item scale asks participants to rate how frequently they felt certain ways (such as nervous, "stressed", or unable to control important things in their lives) on a scale from 0 (Never) to 4 (Very often). Total scores range from 0-40; higher scores indicate higher levels of perceived stress.

Secondary Outcome Measures

Name	Time	Method
Change in P300 amplitude to self vs. other name	1 week post psilocybin therapy	Amplitude of the P300 response to hearing one's own name vs. another stranger's name
Change in blood inflammatory markers	acute on same day as psilocybin therapy	V-PLEX Neuroinflammation Panel-1 Human Kit -The ProcartaPlex Human Inflammation Panel 20plex enables the exploration of immune function by analyzing 20 protein targets in a single well using Luminex xMAP technology.
Number of participants reporting adverse events	8-week follow-up	The total number of participants reporting adverse events from the time of psilocybin administration through the 8 week follow-up.
Mean severity of adverse events	8-week follow-up	The mean severity of adverse events reported from the time of psilocybin administration through the 8-week follow-up. Severity of adverse events will be rated using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0: 1 = Mild, 2 = Moderate, 3 = Severe; 4 = Life threatening; 5 = Death.

Trial Locations

Locations (1)

Univeristy of Southern California Brain and Creativity Institute; 🇺🇸 Los Angeles, California, United States