Nicotine Patch for Marijuana Withdrawal

Study Overview
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Brief Summary
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The purpose of this 3-year trial is to test the efficacy of transdermal nicotine patch versus placebo patch on marijuana withdrawal symptoms in cannabis-dependent individuals, using a randomized, double-blind, and placebo-controlled design. This proposal is in response to RFA-DA-10-016(R01) Medications Development for Cannabis-Related Disorders. Consistent with the goals of this RFA, the overall goal of the proposed project is to assess the impact of transdermal nicotine patch (TNP) on marijuana (MJ) withdrawal (negative affect and craving motivated by negative affect) symptoms in MJ-dependent individuals.

Detailed Description
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The aim of this proposal is to accurately assess the effects of TNP on MJ withdrawal symptoms across 15 days of biochemically confirmed MJ abstinence using a placebo-controlled, double-blind, randomly assigned treatment design, while closely monitoring any potential adverse effects, including changes in nicotine use and dependence. To achieve these goals, 116 carefully screened cannabis-dependent individuals (58 female) will be randomly assigned to one of two doses (0 mg or 7mg nicotine) of TNP (transdermal nicotine patch) while they abstain from MJ for 15 days. Subjects will be administered a follow-up phone interview 30 days after the termination of treatment to assess the effects of nicotine-patch treatment on: 1) frequency of nicotine and tobacco smoking intake, 2) Fagerstrom Test of Nicotine Dependence (FTND)-assessed nicotine dependence, 3) new use of nicotine during the time since completion of the study, and 4) marijuana and other drug use patterns. Large financial contingencies will be used to provide a high degree of abstinence and study completion. This will be the first adequately powered study to assess the effects of TNP on MJ negative affect-related withdrawal symptoms and urges to use MJ. Withdrawal patterns and abstinence will be assessed in two groups of MJ-dependent individuals: 1) those who rarely or never smoke tobacco, and 2) those who smoke four or fewer tobacco cigarettes per day (very-light tobacco smokers). A stratified randomization method will be used to control for gender and tobacco-smoker status. It is hypothesized that MJ withdrawal symptoms will be less severe in the group assigned to the 7 mg patch than in the group assigned to the placebo. It is also hypothesized that individuals high in anxiety/neuroticism and those high in aggression/hostility will exhibit greater benefits from TNP than those low in these traits. Given that no gender differences were observed in our preliminary study, gender differences are not predicted. The over-the-counter availability, minimal abuse risks, and minimal adverse side-effects associated with TNP would make it an ideal and highly implementable treatment for MJ dependence if it can be demonstrated to be efficacious in reducing MJ withdrawal symptoms.

Official Title
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Nicotine for Marijuana Withdrawal

Conditions
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Marijuana Dependence

Intervention / Treatment
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* Drug: Nicotine
* Drug: Placebo Patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male cannabis-dependent MJ smokers aged 18 years or older will be recruited. Inclusion criteria include cannabis dependence as assessed by a Diagnostic and Statistical Manual (DSM-IV)-based structured interview and MJ use on 10-28 occasions per week and be willing to abstain for 15 days. Only individuals who are in good mental and physical health, with a BMI of 17-30 kg/m2, as verified by health questionnaires and the Structured Clinical Interview for DSM-IV (SCID), will participate in this study. Potential subjects will be asked to indicate, on a scale of 1-10, how strong they currently want to quit smoking MJ (from 1 = not at all to 10 = very strong) and will also be assessed with the four-item MJ Stages of Change. Additionally, subjects will fulfill one of two criteria: 1) not smoke or use other tobacco products or 2) smoke tobacco cigarettes or use other nicotine delivery systems (e.g., hookah, cigars, chewing tobacco) fewer than 5 times per day (on average) for the past year. Current use of MJ and tobacco will be verified by detectable urine Tetrahydrocannabinol (THC) and nicotine metabolites. All subjects will be required to provide four pre-quit baseline urine samples. The mean creatinine-normalized THC concentration across these samples must be of 175 ng/ml or greater based. - Exclusion Criteria: Criteria include meeting DSM-IV criteria for current abuse or dependence on a substance other than MJ, nicotine, or caffeine, using psychoactive substances (other than MJ, alcohol, nicotine, & caffeine) 6+ times/month, testing positive for stimulants, antidepressants, anxiolytics, and/or opiates (10-panel urine drug test), testing above a salivary cotinine concentration of 150 ng/ml during the initial screening, using creatinine or creatinine-containing supplements, testing positive for adulteration of urine samples, consuming more than 6 alcoholic drinks per day continuously for a month, mental disorders including bipolar disorder, schizophrenia, psychotic symptoms, currently, recently, or ever chronically at significant suicidal risk or experiencing violent thoughts or current major depression. Others that will be excluded include women who are pregnant, lactating, not taking precautions to avoid pregnancy, individuals with significant physical disorders or unstable physical disorders that may represent a severe untreated condition, such as hypertension, as well as those with less than a high school education or equivalent, primary language other than English, and those with significant cognitive impairment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Patch<br>Placebo patch for 15-day quit period | Drug: Placebo Patch<br>* Placebo patch<br>* Other names: Placebo patch from Rejuvenations Lab;|
| Active Comparator: Nicotine Patch<br>7 mg Habitrol nicotine patch-15 day quit period | Drug: Nicotine<br>* Nicotine patch 7mg<br>* Other names: Habitrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Mood Scale Total Negative Affect (Tension + Depression + Anger) | POMS Total negative affect was assessed during the final pre-quit baseline session and the 8 post-quit sessions (1, 3, 5, 7, 9, 11, 13, and 15 days post-quit). The Total negative affect score has a minimum potential value of 0 = best possibly level and a maximum value of 154 = worst possible level. | 16 days (prequit baseline and 15 days of abstinence) | 
| Marijuana Withdrawal Questionnaire (MWC) Total Score | The Marijuana Withdrawal Questionnaire Total Score includes items assessing anxiety, depression, irritability, appetite, aggression/anger, sleep disturbance, somatic disturbances, and craving to use marijuana. The potential range of this total score is from 0 = no withdrawal symptoms to 47 = maximally high levels of withdrawal. | 16 days (prequit baseline and at 1, 3, 5, 7, 9, 11, 13, and 15 days of abstinence) | 
| POMS Vigor/Positive Affect (PA) | Profile of Mood State questionnaire Vigor/Positive Affect scale. The potential range of the Vigor/Positive Affect scale is from 0 (no vigor) to 32 (maximally high vigor score). | 16 days (baseline through day 15 of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patch Guess and Attributions Questionnaire | The Patch Guess and Attributions Questionnaire assesses which type of patch (active versus placebo) the subject believes that he or she was given during the study. This assessment was made at end of treatment (Day 15 of abstinence), the last day on a patch. Scores range from 0 percent to 100 percent chance of being on the nicotine patch for those actually on the placebo patch and from 0 percent to 100 percent chance of being on the nicotine patch for those subjects actually on the nicotine patch. Each subject was asked to indicate the percentage chance that he or she was on the nicotine (as opposed to the placebo) patch. The mean values reported below are the group mean percentage averages. | Day 15 of abstinence | 
| Systolic Blood Pressure (SBP) | Systolic blood pressure was measured in mmHg during each experimental session prior and subsequent to quitting marijuana. | From baseline to Day 15 of abstinence | 
| Tobacco and Nicotine Intake | Nicotine intake was assessed by self-reported tobacco cigarettes per month (30 days) at baseline (prior to treatment) and also across the 30 days starting immediately after the end of treatment. | Basesline 30 days prior to study and during the 30 days following the 15-day abstinence phase. | 
| Urinary Tetrahydrocannabinol (THC) Concentration in ng/ml. | Tetrahydrocannabinol (THC) Intake assessed by assessing urine sample creatinine corrected THC in ng/ml urine. | across baseline and at 3, 5, 7, 9, 11, 13, and 15 days of abstinence | 
| Heart Rate | Heart rate measured during laboratory assessment sessions. | Baseline through Day 15 of abstinence | 
| Diastolic Blood Pressure (DBP) | Diastolic blood pressure measured during each of the experimental sessions-- baseline through 15-days post-quit. | From baseline to Day 15 of abstinence | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Marijuana, Drug withdrawal symptoms, Nicotine