Mindfulness-assisted Psychedelic Therapy

NCT06233344 | Recruiting Phase 2 FDA Drug

• 1 other identifier: APP-23-05800
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Mental Health

Keywords

Psychedelic therapy; Psilocybin; Mindfulness

Outcome Measures

Primary Outcomes (2)

• Retention at 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)

  8-week follow-up

• Change in stress symptoms

  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.

  8-week follow-up

Secondary Outcomes (4)

• Change in P300 amplitude to self vs. other name

  1 week post psilocybin therapy

• Change in blood inflammatory markers

  acute on same day as psilocybin therapy

• Number of participants reporting adverse events

  8-week follow-up

• Mean severity of adverse events

  8-week follow-up

Study Arms (2)

Mindfulness-assisted psilocybin therapy

EXPERIMENTAL

8 weeks of mindfulness training plus one 25mg dose of psilocybin

Drug: Psilocybin plus mindfulness training

Psilocybin only

ACTIVE COMPARATOR

One 25mg dose of psilocybin

Drug: Psilocybin

Interventions

Psilocybin plus mindfulness training DRUG

Participants will receive a single 25 mg dose of psilocybin under the supervision of study therapists. The psilocybin dosing session will take place approximately halfway through an 8-week mindfulness training course. The mindfulness training course will consist of weekly 2-hour classes with experienced mindfulness teachers; participants will be encouraged to practice mindfulness for 45 minutes per day between classes.

Mindfulness-assisted psilocybin therapy

Psilocybin DRUG

Participants will receive a single 25 mg dose of psilocybin under the supervision of study therapists.

Psilocybin only

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

Eligible participants will be: * Adults of any race, ethnicity, or gender who are age 25 years or older * Have not had formal mindfulness training * Have not previously used classic psychedelics * Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the morning of the drug session day. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on the session day. * Agree to refrain from using any psychoactive drugs, including alcoholic beverages and nicotine, within 24 hours of each drug administration. The exception is caffeine. * Agree not to take any PRN medications on the mornings of drug sessions * Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of psilocybin administration. * Agree that for one week before the drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals. Participants will be excluded if they present with any of the following: * Prior exposure to formal mindfulness or meditation training * Previous use of psilocybin or other psychedelic drugs (LSD, mescaline, DMT/ayahuasca, 5-methoxy-DMT) * Current use of tricyclic antidepressants, serotonin reuptake inhibitors, antipsychotics, atypical antipsychotics, monoamine oxidase inhibitors (MAOIs), mood stabilizers (lithium), buspirone, mirtazapine, trazodone, or other drugs that modulate the serotonin system. For individuals who have intermittent or PRN use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose. * Current use of St. John's Wort or 5-hydroxytryptophan * Currently taking psychoactive prescription medication on a regular (e.g., daily) basis * Current or lifetime history of schizophrenia, other psychotic disorders, or bipolar I or II disorder; or a first or second degree relative with one of these disorders * Current or recent past (within the past 5 years) history of alcohol or drug dependence (other than caffeine or nicotine) or major depressive episode * Current or recent suicidal ideation (within the past month) or behavior (within the past 6 months), as assessed by a response of "yes" to any of questions in the "Suicidal Ideation" or "Suicidal Behavior" on the C-SSRS at the eligibility screen or baseline session * Current (past two weeks) self-reported risky alcohol use (\>7 drinks/week for women or \>14 drinks/week for men) * Current obsessive-compulsive disorder, dysthymic disorder, panic disorder, dissociative disorder, anorexia nervosa, or bulimia nervosa * Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin * Self-reported use of or positive urine drug screen for amphetamines/methamphetamine, opioids, barbiturates, methadone, cocaine, or PCP at the eligibility screen visit or the psilocybin visit * Positive breath alcohol test at the eligibility screen visit or the psilocybin visit (BrAC \> 0.01) * Current pregnancy, planned pregnancy in the next 6 months (at phone screen or eligibility screen), positive urine pregnancy test (for participants of childbearing potential) at the eligibility screen or the psilocybin session, or current breastfeeding * Unwilling to use a medically-accepted highly effective form of birth control (such as hormonal implants, intrauterine devices (IUDs), hormonal birth control pills, surgical sterility, or other methods deemed highly effective (\<1% failure rate) by the study physician) during the study (applies to male participants as well as female participants of childbearing potential) * Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrillation, QTc greater than 450 msec), artificial heart valve, or TIA in the past year * Epilepsy with history of seizures * Current unstable medical condition (including uncontrolled or poorly controlled hypertension - resting blood pressure greater than 140 (systolic) or 90 (diastolic) mmHg at the eligibility screening will be reviewed by the study physician and participants with stable hypertension will be asked to follow-up with their primary care physician to initiate appropriate hypertensive treatment prior to proceeding) * Diabetes (type 1 or 2) with insulin dependence; if taking oral hypoglycemic agent, then no history of hypoglycemia * Any other medical condition that may be incompatible with safe exposure to psilocybin * Inability to speak English * Inability to provide informed consent

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

Univeristy of Southern California Brain and Creativity Institute

Los Angeles, California, 90089, United States

RECRUITING

Related Links

• Study website to assess eligibilty and enroll in study

MeSH Terms

Conditions

Psychological Well-Being

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Personal Satisfaction; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Baruch R Cahn, MD, PhD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Baruch R Cahn, MD, PhD

CONTACT

858-366-3615; bcahn@usc.edu

Mary Falcone, PhD

CONTACT

mary.falcone@med.usc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor of Psychiatry & Behavioral Sciences

Model Details: This is a randomized, open-label, parallel arm trial.

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: January 31, 2024
• Study Start: July 30, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)