Varenicline for Co-occurring Cannabis and Tobacco Use

Study Overview
=================
Brief Summary
-----------------
Pilot, eight week, open-label, within-subject cross over trial of four weeks of standard clinical care (SCC) in an outpatient substance abuse treatment program and four weeks of SCC and varenicline among current and former tobacco smokers with frequent cannabis use.

Detailed Description
-----------------
Treating co-occurring cannabis and tobacco use disorders might reduce the health burdens associated with both substances. However, few studies have evaluated pharmacological interventions, in combination with behavioral treatment, to address co-occurring cannabis and tobacco use; these are limited by high participant attrition, poor adherence to interventions, and lack of control. Participants were recruited from an urban, outpatient substance abuse treatment program that offers both intensive behavioral counseling and medication-assisted treatment (MAT) for opioid use disorder. The investigators selected these clinical sites because the investigators have successfully recruited and retained participants from these sites in prior clinical trials, and anticipated that they would find a high prevalence of persons with frequent cannabis use.

Official Title
-----------------
Feasibility and Preliminary Effectiveness of Varenicline for Co-occurring Cannabis and Tobacco Use

Conditions
-----------------
Cannabis Dependence, Tobacco Dependence

Intervention / Treatment
-----------------
* Drug: Standard clinical care and varenicline
* Other: Standard clinical care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to speak English Uses cannabis at least 5 days in the past 7 days Current or former tobacco smoker Has not taken varenicline in the past 30 days Not pregnant, trying to conceive or breastfeeding Able to provide informed consent Test positive for cannabinoids by urine toxicology Exclusion Criteria: Unstable medical or psychiatric illness Opioid use disorder was initially exclusionary but eligibility criteria were revised after 32 individuals were screened to facilitate recruitment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard clinical care<br>Four weeks of medication-assisted treatment (MAT) with standard clinical care (SCC). MAT includes individual counseling that uses motivational and cognitive behavioral strategies, may address cannabis or tobacco use, and is delivered by trained substance abuse counselors. | Other: Standard clinical care<br>* Standard clinical care includes methadone clinic-based individual behavioral counseling at least once a month using motivational and cognitive behavioral strategies<br>|
| Active Comparator: Standard clinical care and varenicline<br>Four weeks of MAT with standard clinical care plus varenicline therapy (SCC and VT). Varenicline therapy included a one-month supply of standard doses: 0.5mg for the first three days, 0.5mg twice a day for the following four days, and 1 mg twice a day for the remaining 21 days. MAT includes individual counseling that uses motivational and cognitive behavioral strategies, may address cannabis or tobacco use, and is delivered by trained substance abuse counselors. | Drug: Standard clinical care and varenicline<br>* Standard clinical care includes methadone clinic-based individual behavioral counseling at least once a month using motivational and cognitive behavioral strategies. Varenicline therapy includes a one month's supply of the medication in standard doses: 0.5 mg for 3 days, 0.5 mg twice a day for 4 days, then 1 mg twice a day for 21 days.<br>* Other names: stand clinical care and Chantix;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enrollment rate | proportion of screened subjects eligible and willing to participate | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retention rates of participants | Retention rate was determined as the proportion of completed study visits. | Week 8 | 
| Medication adherence measured by pill count. | Proportion of pills taken as prescribed. | Weeks 2, 4, 6, and 8. | 
| Incidence of Treatment-Emergent Adverse Events among participants as assessed by participant self-report on a structured questionnaire of common varenicline side effects. | Participants self-reported adverse events using a structured questionnaire of common varenicline symptoms. The questionnaire was developed ad hoc. | Weeks 2, 4, 6, and 8. | 
| Incidence of Treatment-Emergent psychiatric symptoms reported by participants as measured by the MINI International Neurospsychiatric Interview | To address psychiatric symptoms, the MINI International Neuropsychiatric Interview (M.I.N.I) was used. The Mini-International Neuropsychiatric Interview (M.I.N.I.) is a short structured diagnostic interview, developed jointly by psychiatrists and clinicians in the United States and Europe, for DSM-IV and ICD-10 psychiatric disorders. | Weeks 2, 4, 6, and 8. | 
| Cannabis craving as measured by the marijuana craving questionnaire. | The Marijuana Craving Questionnaire (MCQ) is a valid and reliable, self-report instrument with 47 items rated on a 7-point Likert scale from 1 (strongly disagree) to 7 (strongly agree). The 47 items are grouped by certain characteristics and the score of each of resulting groups correlates to the intensity of the four craving dimensions (compulsivity, emotionality, expectancy, and purposefulness). Total possible scores range from 47- 329. | Weeks 2, 4, 6, and 8. | 
| Cannabis withdrawal as measured by the marijuana withdrawal checklist. | Cannabis withdrawal is measured by the 15-item version of the marijuana withdrawal checklist. In the marijuana withdrawal checklist, respondents rate each symptom experienced during their most recent period of marijuana abstinence, based on a 4-point scale where 0 = none, 1 = mild, 2 = moderate, and 3 = severe. A total MWC score is obtained by summing the severity ratings. Total scores range from 0 - 45, with 0 as the least severe score and 45 as the highest score. | Weeks 2, 4, 6, and 8. | 
| Quantity of past two week cannabis use as measured by the timeline follow back method. | Measured using the timeline follow-back method, a method in which participants use a physical calendar to note the number of days over a specified period of time during which they used cannabis. | Weeks 2, 4, 6, and 8. | 
| Quantity of past two week tobacco use as measured by the timeline follow back method. | Measured using the timeline follow-back method, a method in which participants use a physical calendar to note the number of days over a specified period of time during which they used tobacco. | Weeks 2, 4, 6, and 8. | 
| Frequency of past two week cannabis use as measured by percentage of days self-reported in the timeline follow-back method. | Measured using the timeline follow-back method, a method in which participants use a physical calendar to note the number of days over a specified period of time during which they used cannabis. | Weeks 2, 4, 6, and 8. | 
| Frequency of past two week tobacco use as measured by percentage of days self-reported in the timeline follow-back method. | Measured using the timeline follow-back method, a method in which participants use a physical calendar to note the number of days over a specified period of time during which they used tobacco. | Weeks 2, 4, 6, and 8. | 
| Cannabis abstinence as measured by urine toxicology test. | Cannabis abstinence was measured by a urine toxicology test, defined as a tetrahydrocannabinol level less than 50 ng/ml. Urine samples were analyzed at a commercial laboratory. | Weeks 2, 4, 6, and 8. | 
| Biochemically verified tobacco abstinence as measured by a Bedfont Smokerlyzer carbon monoxide reader. | Tobacco abstinence was assessed via a Bedfont Smokerlyzer carbon monoxide reader and operationalized as a reading of less than 8 p.p.m. | Weeks 2, 4, 6, and 8. | 
| Cannabis abstinence as measured by timeline follow back method. | Measured using the timeline follow-back method, a method in which participants use a physical calendar to note the number of days over a specified period of time during which they used cannabis. Abstinence was defined as self-reported two-week abstinence. | Weeks 2, 4, 6, and 8. | 
| Tobacco abstinence as measured by timeline follow back method. | Measured using the timeline follow-back method, a method in which participants use a physical calendar to note the number of days over a specified period of time during which they used tobacco. Abstinence was defined as self-reported two-week abstinence. | Weeks 2, 4, 6, and 8. | 
| Mean expired carbon monoxide as measured by Bedfont Smokealyzer carbon monoxide reader. | Measured by Bedfont Smokealyzer carbon monoxide reader. | Weeks 2, 4, 6, and 8. | 
| Incidence of Treatment-Emergent suicidal ideation reported by participants as measured by the Columbia Suicide Severity Rating Scale. | The Columbia Suicide Severity Rating Scale contains 6 yes or no questions in which respondents are asked to indicate whether they have experienced several thoughts or feelings relating to suicide over the past month and behaviors over their lifetime and past 3 months. An answer of yes to any of the six questions may indicate a need for referral to a trained mental health professional and an answer of yes to questions to the last three questions (4,5, 6) indicate high-risk. | Weeks 2, 4, 6, and 8. |