Nicotine Dependence
Conditions
Keywords
Psilocybin, Smoking cessation
Brief summary
One of the most promising lines of investigation for the therapeutic use of hallucinogens in the 1960s and 1970s was in the treatment of drug dependence. The investigators propose to examine psilocybin administration combined with a structured smoking cessation treatment program in nicotine dependent individuals in order to provide preliminary data on the efficacy of this combined treatment for smoking cessation. Prior work in the investigators laboratory has shown that under carefully prepared and supportive conditions, psilocybin administration can facilitate highly salient experiences with enduring personal meaning and spiritual significance. It is plausible that embedding such highly meaningful experiences into a drug dependence cessation attempt may provide an enduring motivation for remaining abstinent. Cigarette smoking is a good model system for studying drug dependence because users are less likely to be challenged by the many social and economic impairments that often accompany dependence on other drugs such as cocaine, heroin, or alcohol. More specifically, the investigators propose to conduct a randomized controlled comparative efficacy study in which either psilocybin or transdermal nicotine patch are administered under highly supportive conditions to individuals who are nicotine-dependent cigarette smokers, who have had multiple unsuccessful quit attempts, and who continue to desire to quit smoking. Other than nicotine dependence, participants will be healthy. Fifteen participants have already completed a preliminary open-label pilot-study with no control condition. Eighty additional participants will be enrolled and randomized to either psilocybin (n=40), or nicotine patch (n=40) treatment. Participants will receive a 13-week course of cognitive behavioral therapy for smoking cessation, with Target Quit Date set for week 5. After several preparation meetings with study monitors, participants will have either a single day-long psilocybin session using a high dose (30 mg/70 kg), or a standard 8 to 10-week course of nicotine patch treatment. Participant smoking status will be assessed repeatedly for 8 weeks after the Target Quit Date, including biological verification of smoking status through breath and urine samples. Smoking status will also be assessed at three follow up sessions approximately 3, 6, and 12 months after the Target Quit Date. Additionally, 50 of these participants (25 per treatment condition) will undergo MRI scanning before and after Target Quit Date to assess the brain-based mechanisms associated with these treatments. Individuals assigned to the nicotine patch study treatment condition will be eligible to undergo an optional high dose psilocybin session after completing the 6-month follow-up meeting.
Interventions
DRUGPsilocybin-assisted treatment
Participants will be administered 30 mg/70 kg psilocybin. Preliminary evidence from our ongoing psilocybin dose-effects study suggests that this dose is associated with mystical-type experiences.
DRUGNicotine Replacement Therapy (NRT)
Sponsors
Beckley Foundation
Heffter Research Institute
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 6 Months | From the target quit date to the 6-month follow up | Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 6-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 3 Months | From the target quit date to the 3-month follow up | Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 3-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report. |
| Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 12 Months | From the target quit date to the 12-month follow up | Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 12-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Psilocybin-assisted Treatment Participants will receive a 13-week cognitive behavioral intervention for smoking cessation, with a high dose of psilocybin (30mg / 70kg) to be administered on the Target Quit Date in week 5.
Psilocybin-assisted treatment: Participants will be administered 30 mg/70 kg psilocybin. Preliminary evidence from our ongoing psilocybin dose-effects study suggests that this dose is associated with mystical-type experiences. | 42 |
| Nicotine Replacement Therapy (NRT) First, Then Psilocybin-assisted Treatment Participants will receive a 13-week cognitive behavioral intervention for smoking cessation, with a standard 8 to 10-week regimen of NRT to be administered beginning on the Target Quit Date in week 5. NRT for this study will be a transdermal nicotine patch administered according to recommended label usage (For individuals who smoke more than 10 cigarettes per day: 21mg daily weeks 1-6, 14mg daily weeks 7-8, 7mg daily weeks 9-10. For individuals who smoke 10 or less cigarettes per day: 14mg daily for weeks 1-6, 7mg daily for weeks 7-8).
Participants who were initially assigned to the Nicotine Replacement Therapy (NRT) Arm/Group had the option to cross-over to Psilocybin-assisted Treatment at 6 months. | 40 |
| Total | 82 |
Baseline characteristics
| Characteristic | Nicotine Replacement Therapy (NRT) First, Then Psilocybin-assisted Treatment | Total | Psilocybin-assisted Treatment |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 4 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 78 Participants | 38 Participants |
| Age, Continuous | 46.75 years STANDARD_DEVIATION 12.26 | 47.63 years STANDARD_DEVIATION 12.05 | 48.48 years STANDARD_DEVIATION 11.93 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 73 Participants | 38 Participants |
| Region of Enrollment United States | 40 Participants | 82 Participants | 42 Participants |
| Sex: Female, Male Female | 14 Participants | 33 Participants | 19 Participants |
| Sex: Female, Male Male | 26 Participants | 49 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 40 | 0 / 26 |
| other Total, other adverse events | 37 / 42 | 31 / 40 | 25 / 26 |
| serious Total, serious adverse events | 0 / 42 | 1 / 40 | 1 / 26 |
Outcome results
Primary
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 6 Months
Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 6-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report.
Time frame: From the target quit date to the 6-month follow up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Psilocybin-assisted Treatment | Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 6 Months | 17 Participants |
| Nicotine Replacement Therapy (NRT) | Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 6 Months | 4 Participants |
p-value: 0.00395% CI: [1.99, 23.26]Regression, Logistic
Secondary
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 12 Months
Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 12-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report.
Time frame: From the target quit date to the 12-month follow up
Population: Participants with data collected
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Psilocybin-assisted Treatment | Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 12 Months | 15 Participants |
| Nicotine Replacement Therapy (NRT) | Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 12 Months | 0 Participants |
| Cross-over to Psilocybin-assisted Treatment | Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 12 Months | 7 Participants |
Secondary
Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 3 Months
Cigarette smoking abstinence from the target quit (allowing for an initial 14-day grace period) to the 3-month follow up, as verified by breath carbon monoxide, urine cotinine, and retrospective self-report.
Time frame: From the target quit date to the 3-month follow up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Psilocybin-assisted Treatment | Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 3 Months | 20 Participants |
| Nicotine Replacement Therapy (NRT) | Prolonged Abstinence: Biologically Verified Cigarette Smoking Abstinence for 3 Months | 12 Participants |