Recruiting

Phase 2

Psilocybin5-HT2A Agonist Psilocybin in the Treatment of Tobacco Use Disorder

Sponsor:

Johns Hopkins University

Code:

NCT05452772

Conditions

Tobacco Use Disorder

Eligibility Criteria

Sex: All

Age: 21+

Healthy Volunteers: Accepted

Interventions

Psilocybin

Niacin

Study Details

Brief summary:

This is a multi-site, double-blind, randomized clinical trial of the 5-HT2A receptor agonist psilocybin for smoking cessation. Four sites with experience in conducting psilocybin research will be involved in this trial: Johns Hopkins University (JHU), the University of Alabama at Birmingham (UAB), and New York University (NYU). The proposed study will treat 66 participants (22 at each site), randomized to receive either: 1) oral psilocybin (30 mg in session 1 and either 30 mg or 40 mg in session 2); or 2) oral niacin (150 mg in session 1 and either 150 mg or 200 mg in session 2), with sessions 1 week apart.

Conditions

Tobacco Use Disorder

Study ID

NCT05452772

Start date

Nov 1, 2023

Status verified date

Jun, 2026

Completion date

May, 2027

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 21+

Healthy Volunteers: Accepted

Inclusion Criteria:

21 years old or older
Be a daily smoker (minimum of 5 cigarettes/day on a typical day and breath CO of 6 or greater at screening) with multiple unsuccessful previous quit attempts, and report a continued desire to quit smoking
Read, write, and speak English
Agree to abstain from smoking for the psilocybin/niacin session from 1 hour before psilocybin/niacin administration until at least 8 hours afterward
Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 hours of psilocybin/niacin administration
Be healthy as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis lab tests. See Exclusion Criteria below for specific ECG and specific blood test criteria

Exclusion Criteria:

The use of e-cigarettes or tobacco products other than machine-manufactured combustible cigarettes (e.g., cigarillos) on more than 5 of the previous 30 days
Women who are pregnant (positive pregnancy test) or nursing, or are not practicing an effective means of birth control
Positive urine drug screen for illicit drugs (excluding cannabis)
Positive urine breath test for alcohol. Participants with positive tests will be rescheduled
For blood samples, the following lab values will be exclusionary: transaminases greater than x2 the upper limit of normal lab reference range, hemoglobin less than 11 g/d, and creatinine clearance < 40 ml/min using the Cockroft-Gault equation.
For ECG screening: The ECG will be read by a cardiologist. Corrected heart rate (QTc) greater than 450 msec will be excluded.
Patients who have baseline vital signs that exceed the following measurements will be excluded from participation: Systolic blood pressure (SBP) > 139 mmHG, diastolic blood pressure (DBP)> 89 mmHG, and heart rate of <=95 beats per minute (BPM). The investigators will perform serial heart rate monitoring with 3 total attempts. That is, heart rate must be <=95 bpm on one of these attempts to be included in the study.
Currently taking on a regular basis (e.g., daily) antidepressants of any drug class, antipsychotics, or monoamine oxidase inhibitors (MAOIs), or serotonin-acting dietary supplements (e.g., 5-hydroxy- tryptophan, St. John's wort). Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, or uridine diphosphate glucuronosyltransferase 1-9 (UGT1A9) inhibitors or uridine diphosphate glucuronosyltransferase 1-10 (UGT1A10) inhibitors such as phenytoin, regorafenib, eltrombopag. For individuals who have intermittent or "as needed" 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 medications for smoking cessation (i.e., varenicline, nicotine replacement products, bupropion)
Current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head trauma (loss of consciousness > 24 hours), or central nervous system (CNS) tumor
Recent (within the past 12 months) or an extensive history of psychedelic use (>20 lifetime uses)
Current or past history of meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I or II Disorder. Current or past history within the last 5 years of meeting DSM-5 criteria for alcohol or drug use disorder (excluding caffeine and nicotine) or severe major depression
Recent (past year) history of suicidal behavior or attempt or high-level current suicidal ideation assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Have a first- or second-degree relative with schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), or bipolar I or II disorder
Currently meets DSM-5 criteria for Dissociative Disorder, Anorexia Nervosa, Bulimia Nervosa, Major Depression, or Post-traumatic Stress Disorder

Study Design

Enrollment

66 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Psilocybin

30 mg in session 1 and either 30 mg or 40 mg in session 2, with sessions 1 week apart. Dosing will be based on participants' responses to the Mystical Experiences Questionnaire (MEQ30), taken at the end of their first session. Participants with a score ≥60% of the maximum on the MEQ30 will remain at a dose of 30 mg of psilocybin for the second session. Participants with an MEQ30 score below 60% will receive a dose of 40 mg for the second session.

active comparator: Niacin

150 mg in session 1 and either 150 mg or 200 mg in session 2, with sessions 1 week apart. Dosing will be based on participants' responses to the Mystical Experiences Questionnaire (MEQ30), taken at the end of their first session. Participants with a score ≥60% of the maximum on the MEQ30 will remain at a dose of 150 mg niacin for the second session. Participants with an MEQ30 score below 60% will receive a dose of 200 mg niacin for the second session.

Interventions

Psilocybin

Participants will received two psilocybin sessions, 1 week apart

Niacin

Participants will received two niacin sessions, 1 week apart

Primary outcome measure

Potential Efficacy (Smoking Cessation) [ Time Frame: 12 months ]

Central Contacts and Locations

Central contacts

Matthew Johnson, Ph.D

410-550-0056 mwj@jhu.edu

Gideon Naudé, Ph.D.

410-550-2774 gnaude1@jhmi.edu

Locations

University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35294

Contacts

Seher Premani, M.P.H.

205-975-7721 spremani@uab.edu

Lindsey Owens, M.A.

205-975-7721 ltowens@uab.edu

Principal Investigator:

Peter Hendricks, Ph.D.

More Information

Sponsor

Johns Hopkins University

Last update posted

Jun 29, 2026

Last verified

Jun, 2026

Keywords

Smoking Cessation
Smoking
Cigarettes
Cigarette Smoking

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-06-29.