Psilocybin-facilitated Smoking Cessation Treatment: A Pilot Study
Randomised, parallel-group study (n=82 actual) comparing a single high-dose psilocybin session (30 mg/70 kg) plus CBT versus standard transdermal nicotine patch plus CBT for nicotine-dependent smokers.
Detailed Description
Randomised, parallel-group comparative efficacy trial enrolling nicotine-dependent adults who receive a 13-week cognitive behavioural smoking-cessation programme with either a single high-dose psilocybin session (30 mg/70 kg) on the Target Quit Date or an 8–10 week transdermal nicotine-patch regimen.
Outcomes include repeated biologically verified smoking-status assessments through 8 weeks post-quit and follow-ups at ~3, 6 and 12 months; a subset (n=50) undergo MRI pre- and post-target quit date to probe neural mechanisms.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Psilocybin-assisted
experimental13-week CBT with a single high-dose psilocybin session (Target Quit Date, week 5).
Interventions
- Psilocybin30 mgvia Oral• single dose• 1 doses total
30 mg per 70 kg; single day-long session
Nicotine patch
active comparator13-week CBT with standard transdermal nicotine patch regimen beginning on Target Quit Date (week 5).
Interventions
- Placebovia Topical• daily
Transdermal nicotine patch per label: for >10 cig/day: 21 mg daily weeks 1–6, 14 mg weeks 7–8, 7 mg weeks 9–10; for ≤10 cig/day: 14 mg weeks 1–6, 7 mg weeks 7–8
Participants
Inclusion Criteria
- Inclusion Criteria:
- 21 to 65 years old.
- Have given written informed consent.
- Have a high school level of education.
- Be a daily smoker with multiple unsuccessful previous quit attempts, and report a continued desire to quit smoking.
- Agree to abstain from smoking and alcohol for 24-hours, and caffeine for 12-hours prior to MRI scanning (for MRI participants only).
- Agree to abstain from smoking for the psilocybin session from 1 hour before psilocybin administration until at least 30 hours afterwards.
- Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the morning of drug session day. If the volunteer does not routinely consume caffeinated beverages, he or she must agree not to do so on session day.
- Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 hours of psilocybin administration. Exceptions include caffeine and nicotine.
- 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 laboratory tests.
Exclusion Criteria
- Exclusion Criteria:
- Women who are pregnant (positive pregnancy test) or nursing, or are not practicing an effective means of birth control
- Cardiovascular conditions: uncontrolled hypertension, angina, a clinically significant ECG abnormality (e.g., atrial fibrilation), TIA in the last 6 months stroke, peripheral or pulmonary vascular disease
- Epilepsy with history of seizures
- Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
- Currently taking psychoactive prescription medication on a regular basis
- Currently taking on a regular (e.g., daily) basis any medications having a primary centrally-acting pharmacological effect on serotonin neurons or medications that are MAO inhibitors. For individuals who have intermittent or PRN 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.
- Have HIV or Syphilis.
- Have any current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head trauma, or CNS tumor.
- Morbidly obese, or severely underweight as determined by medical examination.
- Not suitable to undergo an MRI session due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia (for MRI participants only).
- Current or past history of meeting DSM-IV 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-IV criteria for alcohol or drug dependence (excluding caffeine and nicotine) or severe major depression.
- 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-IV criteria for Dissociative Disorder, Anorexia Nervosa, Bulimia Nervosa, Major Depression, or Post-traumatic Stress Disorder.
Primary Results(4 publications)
Participants
Adverse Events (from all publications)
| Arm / Group | n | Any TEAE | Severe | Serious | Discont. |
|---|---|---|---|---|---|
| Psilocybin-assistedexperimental | 15 | — | — | 0(0.0%) | — |
| Nicotine patchactive_comparator | — | — | — | — | — |
| Psilocybin-assistedexperimental | 15 | — | — | — | — |
| Psilocybin-assistedexperimental | 15 | — | — | — | — |
| Nicotine patchactive_comparator | — | — | — | — | — |
* The paper states 'no clinically significant adverse events occurred' during the 42 psilocybin sessions. Safety data included acute cardiovascular function, SOCQ ratings for acute adverse psychological effects, next-day headache ratings, and Visual Effects Questionnaire data. One participant reported extreme ratings on SOCQ (7%) and five others reported strong ratings of fear/insanity/feeling trapped (33%), but these were managed by staff and resolved by the end of the session. Eight participants reported at least one post-psilocybin headache (mean duration 5.8h, severity mild).
* This was an open-label pilot study with no active comparator arm (nicotine patch) used in the reported results; the study focused on psilocybin-assisted treatment.
* Pilot results reported: physiological adverse effects limited to mild post-session headache and modest acute elevations in blood pressure and heart rate. Six volunteers (40%) reported acute challenging (fearful, anxiety-provoking) psilocybin session experiences.
* The paper is a qualitative analysis of a pilot study. While it discusses 'challenging experiences' and 'withdrawal symptoms', it does not provide a formal summary table of TEAE counts. The study was open-label.
* No data provided for this arm in the text; the study focused on a psilocybin-facilitated intervention.
Study Details
- StatusCompleted
- PhasePhase NA
- Typeinterventional
- DesignRandomized
- Target Enrollment82 participants
- TimelineStart: 2008-09-01End: 2023-12-01
- Compounds
- Topic
Study Team
Sponsors & Collaborators
- Johns Hopkins UniversityPrimary Sponsor
- Beckley Med FoundationCollaborator
- Ketamine Research InstituteCollaborator
Investigators
- MJMatthew Johnson