Tobacco Use Disorder
Conditions
Keywords
Smoking Cessation, Smoking, Cigarettes, Cigarette Smoking
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.
Detailed description
This is a multi-site, double-blind, randomized clinical trial of the 5-HT2A receptor agonist psilocybin for smoking cessation. The investigators previously conducted an open-label pilot trial (N = 15) of psilocybin paired with cognitive behavior therapy (CBT). Data showed a biologically-verified 7-day point-prevalence abstinence rate of 67% at 12 months and 60% at 2.5 years (continuous abstinence rates: 53% and 47%, respectively). The investigators are now conducting an open-label randomized comparative efficacy trial of psilocybin vs. nicotine patch, both in combination with CBT. Interim results (N = 44; 22 per group) show greater biologically-verified abstinence rates at 12 months for psilocybin: 7-day point-prevalence: 59% vs. 27%; continuous abstinence: 36% vs. 9%. Despite these promising findings, the investigators have yet to conduct a double-blind study of psilocybin for smoking cessation. Furthermore, previous psilocybin study samples have been largely White with higher socioeconomic status (SES). The current trial will address these issues across four sites with experience in conducting psilocybin research: Johns Hopkins, the University of Alabama at Birmingham (UAB), and New York University (NYU). A diverse sample with regard to ethno-racial identity and SES will be recruited at each site. The proposed double-blind study will treat 66 participants (22 at each site), randomized to receive either: 1) psilocybin; 30 mg in session 1 and either 30 or 40 mg in session 2, with sessions 1 week apart; or 2) niacin; 150 mg in session 1 and either 150 mg or 200 mg in session 2, with sessions 1 week apart. Niacin was selected because it has been used as an active placebo in two previous randomized therapeutic trials of psilocybin, and the FDA has informed the investigators that niacin is the FDA's preferred active placebo for psilocybin. CBT will be administered to both groups and will allow the investigators to test psilocybin's efficacy above and beyond an established treatment approach. Biochemically-confirmed 7-day point-prevalence abstinence will be assessed throughout for up to 12 months. The investigators hypothesize that psilocybin (compared to niacin) will cause increased biologically-confirmed 7-day point-prevalence abstinence at 12-month follow-up. Based on pilot data, the investigators will test cognitive/psychological mediators of treatment response. The investigators hypothesize that psilocybin will be associated with improved cognitive control and decreased anticipation of withdrawal relief (from smoking) 1 day after the target quit date, which will be associated with greater 7-day point-prevalence abstinence at 12- month follow-up. This trial will provide a rigorous test of efficacy in a diverse study sample, and test relevant mechanisms, for an innovative smoking cessation treatment showing potential for substantial efficacy.
Interventions
DRUGPsilocybin
Participants will received two psilocybin sessions, 1 week apart
DRUGNiacin
Participants will received two niacin sessions, 1 week apart
Sponsors
Johns Hopkins University
University of Alabama at Birmingham
New York University
National Institute on Drug Abuse (NIDA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Potential Efficacy (Smoking Cessation) | 12 months | Smoking cessation will be dichotomously coded 7-day point prevalence abstinence at 12-month follow-up. This binary outcome (abstinent versus non-abstinent) will be verified via three measures of recent smoking-(1) timeline follow-back (TLFB), a self-report calendar completed retrospectively by participants indicating the number of cigarettes smoked each day; (2) exhaled carbon monoxide (CO), an objective and biological measure of smoking over approximately the past 24 hours; and (3) urinary cotinine level, an additional biological and objective measure of nicotine exposure and allows for detection of smoking or other nicotine product use over the previous six days. Though these measures are not study outcomes individually, they will verify 7-day point prevalence abstinence at 12-month follow-up - the primary outcome. Specifically, 0 cigarettes reported on the TLFB, breath CO of ≤6 ppm, and urine cotinine levels of \<200ng/mL will be considered smoking abstinence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Smoking Urges (Questionnaire on Smoking Urges; Factor 2) at Visit 5 | Approximately 1 day after the target quit date | The Questionnaire on Smoking Urges is a multidimensional assessment of smoking craving with demonstrated sensitivity to smoking cessation. Participants will respond using a 7-point scale, where 1 = "Strongly Disagree", 4 = "Neither Agree nor Disagree", and 7 = "Strongly Agree". The scale consists of 10 items and scores can range from 10 - 70, with higher scores reflecting stronger urges to smoke. The Questionnaire on Smoking Urges will be administered at Visit 5 - 1 day after the first psilocybin / niacin session (i.e., 1 day after the target quit date), and again at Visit 6. |
| Smoking Urges (Questionnaire on Smoking Urges; Factor 2) at Visit 6 | Approximately 2 days after the target quit date | The Questionnaire on Smoking Urges is a multidimensional assessment of smoking craving with demonstrated sensitivity to smoking cessation. Participants will respond using a 7-point scale, where 1 = "Strongly Disagree", 4 = "Neither Agree nor Disagree", and 7 = "Strongly Agree". The scale consists of 10 items and scores can range from 10 - 70, with higher scores reflecting stronger urges to smoke. The Questionnaire on Smoking Urges will be administered at Visit 6, the day of the second psilocybin / niacin session (i.e., 2 days after the target quit date). |
| Prolonged Abstinence | 12 months | A secondary measure of abstinence will be prolonged abstinence, defined as no smoking at all after the target quit date, with the exception that smoking lapses during an initial 2-week grace period after the target quit date are not counted. |
| Cognitive control (Multi-Source Interference Task) at Screening (Visit 0) | Approximately 4 weeks prior to the target quit date | The Multi-Source Interference Task is a measure of cognitive control that requires participants to inhibit a prepotent response when engaged in a voluntary task-based action. The Multi-Source Interference Task will be administered at screening - approximately 4 weeks prior to the first psilocybin / niacin session (i.e., 4 weeks prior to the target quit date), and again at Visits 5 and 6. |
| Cognitive control (Multi-Source Interference Task) at Visit 5 | Approximately 1 day after the target quit date | The Multi-Source Interference Task is a measure of cognitive control that requires participants to inhibit a prepotent response when engaged in a voluntary task-based action. The Multi-Source Interference Task will be administered at Visit 5 - 1 day after the first psilocybin / niacin session (i.e., 1 day after the target quit date), and again at Visit 6. |
| Smoking Urges (Questionnaire on Smoking Urges; Factor 2) at Screening | Approximately 4 weeks prior to the target quit date | The Questionnaire on Smoking Urges is a multidimensional assessment of smoking craving with demonstrated sensitivity to smoking cessation. Participants will respond using a 7-point scale, where 1 = "Strongly Disagree", 4 = "Neither Agree nor Disagree", and 7 = "Strongly Agree". The scale consists of 10 items and scores can range from 10 - 70, with higher scores reflecting stronger urges to smoke.The Questionnaire on Smoking Urges will be administered at screening - approximately 4 weeks prior to the first psilocybin / niacin session (i.e., 4 weeks prior to the target quit date), and again at Visits 5 and 6. |
| Cognitive control (Multi-Source Interference Task) at Visit 6 | Approximately 2 days after the target quit date | The Multi-Source Interference Task is a measure of cognitive control that requires participants to inhibit a prepotent response when engaged in a voluntary task-based action. The Multi-Source Interference Task will be administered at Visit 6, the day of the second psilocybin / niacin session (i.e., 2 days after the target quit date). |
Countries
United States
Contacts
CONTACTMatthew Johnson, Ph.D
CONTACTGideon Naudé, Ph.D.
PRINCIPAL_INVESTIGATORMatthew Johnson, Ph.D
Johns Hopkins University
Outcome results
None listed