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

5-HT2A Agonist Psilocybin in the Treatment of Tobacco Use Disorder (NCT05452772) is a Phase 2 interventional studying Tobacco Use Disorder, sponsored by Johns Hopkins University. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Tobacco Use Disorder and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 66 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Tobacco Use Disorder subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Who Should NOT Join This Trial: - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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

Treatments Being Tested

DRUG

Psilocybin

Participants will received two psilocybin sessions, 1 week apart

DRUG

Niacin

Participants will received two niacin sessions, 1 week apart

Locations (3)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

University of Alabama at Birmingham

Birmingham, Alabama, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

New York University

New York, New York, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05452772), the sponsor (Johns Hopkins University), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05452772 clinical trial studying?

Who can participate in NCT05452772?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05452772?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05452772. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05452772. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.