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

• Status: Not yet recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-site, double-blind, randomized clinical trial of the 5-HT2A receptor agonist psilocybin for smoking cessation. Three 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA); New York University; University of Alabama at Birmingham
• Treatments: Niacin; Psilocybin

Criteria

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