Clinical TrialTobacco/Nicotine Use Disorder (TUD)PsilocybinPlaceboRecruiting

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

Double-blind, randomised, multi-site trial (n=66) comparing two psilocybin sessions (30 mg; second session 30 or 40 mg) versus active placebo niacin (150 mg; second session 150 or 200 mg) plus CBT for smoking cessation.

Target Enrollment
66 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This multi-site, double-blind randomised trial will recruit 66 daily smokers across Johns Hopkins, UAB, and NYU to test psilocybin plus CBT versus niacin plus CBT for smoking cessation.

Participants receive two dosing sessions one week apart with dose adjustment for session two based on the Mystical Experiences Questionnaire (MEQ30). Primary outcome is biochemically-confirmed 7-day point-prevalence abstinence at 12 months.

Secondary aims include testing cognitive and psychological mediators of treatment response; safety and adverse events are monitored with standard labs, ECG, and clinical assessments.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Therapeutic Protocol

cbt

Study Arms & Interventions

Psilocybin

experimental

Oral psilocybin two-session regimen with dose adjustment per MEQ30.

Interventions

  • Psilocybin30 - 40 mg
    via Oral• two sessions• 2 doses total

    Session 1: 30 mg; Session 2: 30 mg or 40 mg based on MEQ30 score

Niacin

active

Oral niacin two-session active-placebo regimen with dose adjustment per MEQ30.

Interventions

  • Placebo150 - 200 mg
    via Oral• two sessions• 2 doses total

    Session 1: 150 mg; Session 2: 150 mg or 200 mg based on MEQ30; used as active placebo

Participants

Ages
21 – 99
Sexes
Male & Female

Inclusion 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

  • Exclusion Criteria:
  • Use of e-cigarettes or tobacco products other than machine-manufactured combustible cigarettes on more than 5 of the previous 30 days
  • Women who are pregnant or nursing, or are not practising an effective means of birth control
  • Positive urine drug screen for illicit drugs (excluding cannabis)
  • Positive breath test for alcohol; participants with positive tests will be rescheduled
  • Exclusionary lab values: transaminases greater than 2x the upper limit of normal, hemoglobin less than 11 g/d, creatinine clearance < 40 ml/min (Cockcroft-Gault)
  • ECG exclusion: corrected QT (QTc) greater than 450 msec
  • Baseline vitals exclusion: SBP > 139 mmHg, DBP > 89 mmHg, heart rate > 95 bpm (heart rate must be <=95 bpm on one of three attempts to be included)
  • Current regular use of antidepressants, antipsychotics, MAOIs, serotonin-acting dietary supplements, efavirenz, disulfiram, alcohol dehydrogenase inhibitors, or UGT1A9/1A10 inhibitors; for intermittent 'as needed' use, sessions postponed until 5 half-lives after last dose
  • Current use of medications for smoking cessation (varenicline, nicotine replacement, bupropion)
  • Current neurological illness (seizure disorder, frequent migraines on prophylaxis, multiple sclerosis, movement disorders, significant head trauma with LOC > 24 hours, CNS tumour)
  • Recent (within 12 months) or extensive history of psychedelic use (>20 lifetime uses)
  • Current or past history of schizophrenia, psychotic disorder, or bipolar I/II; current or past history within 5 years of alcohol or drug use disorder (excluding caffeine and nicotine) or severe major depression
  • Recent (past year) history of suicidal behaviour or attempt or high-level current suicidal ideation assessed by the C-SSRS
  • First- or second-degree relative with schizophrenia, psychotic disorder, or bipolar I/II
  • Current DSM-5 criteria for dissociative disorder, anorexia nervosa, bulimia nervosa, major depression, or PTSD

Study Details

Locations

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

Your Library