Psilocybin-facilitated Smoking Cessation Treatment: A Pilot Study

Study Overview
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Brief Summary
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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.

Official Title
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Psilocybin-facilitated Smoking Cessation Treatment: A Pilot Study

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: Psilocybin-assisted treatment
* Drug: Nicotine Replacement Therapy (NRT)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psilocybin-assisted treatment<br>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. | Drug: Psilocybin-assisted treatment<br>* 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.<br>* Other names: O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine;|
| Active Comparator: Nicotine Replacement Therapy (NRT)<br>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). | Drug: Nicotine Replacement Therapy (NRT)<br> <br> * Other names: Nicoderm CQ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary cotinine | Urinary cotinine is a biological method used to verify smoking or non-smoking status of participants. | At study intake, then at 3, 6, and 12 month follow up. | 
| Breath CO | Breath Carbon Monoxide (CO) level is a biological method used to verify smoking or non-smoking status of participants. | For 13 weeks during active treatment, then at 3, 6, and 12 month follow up. | 
| MRI scanning | 50 participants will undergo MRI scanning in week 2 before their Target Quit Date, and in week 5 the day after their Target Quit Date. Participants who are biologically verified as smoking abstinent at 3-month follow-up will also complete an additional MRI scan at that time. For all MRI scanning sessions participants will be asked to refrain from smoking for 24 hours prior to the scan. | At 2 weeks (pre), 5 weeks (post), and 3 month follow up (for individuals still abstinent at this time point) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psilocybin, Smoking cessation