Varenicline for Co-occurring Cannabis and Tobacco Use

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

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

Study Overview

• Status: Completed
• Conditions: Cannabis Dependence; Tobacco Dependence
• Intervention / Treatment: Drug: Standard clinical care first, followed by standard clinical care and varenicline; Drug: Standard clinical care and varenicline first, followed by standard clinical care

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. Pilot, eight week, open-label, within-subject cross over trial of four weeks of standard clinical care (SCC) in an outpatient substance use disorder treatment program and four weeks of SCC and varenicline among current and former tobacco smokers with frequent cannabis use. Participants were recruited from an urban, outpatient substance use disorder treatment program that offers both intensive behavioral counseling and medications for opioid use disorder (MOUD). Participants were randomized to receive either SCC or SCC and varenicline first and then were crossed over to receive the opposite intervention. The study consisted of two 4-week treatment periods with no washout period. Outcomes are reported in pooled analyses of all participants in each treatment phase.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard clinical care first, followed by standard clinical care and varenicline; Four weeks of standard clinical care (SCC) in an outpatient substance use disorder treatment program. SCC includes individual counseling, at least once a month, that uses motivational and cognitive behavioral strategies, may address cannabis or tobacco use, and is delivered by trained substance use disorder treatment counselors; and medications for opioid use disorder (MOUD). This is followed by four weeks of SCC plus varenicline treatment (SCC and VT). Varenicline treatment included a gour-week 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.	Drug: Standard clinical care first, followed by standard clinical care and varenicline; Standard clinical care includes substance use disorder treatment program-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.; Other Names: SCC first, then SCC+VT
Experimental: Standard clinical care and varenicline first, followed by standard clinical care; Four weeks of standard clinical care (SCC) plus varenicline treatment (SCC and VT). SCC includes individual counseling, at least once a month, that uses motivational and cognitive behavioral strategies, may address cannabis or tobacco use, and is delivered by trained substance use disorder treatment counselors; and medications for opioid use disorder (MOUD).Varenicline treatment included a gour-week 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. This is followed by four weeks of SCC in an outpatient substance use disorder treatment program, as described above.	Drug: Standard clinical care and varenicline first, followed by standard clinical care; Standard clinical care includes substance use disorder treatment program-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.; Other Names: SCC+VT first, then SCC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enrollment Rate	Percentage of the eleven eligible subjects willing to participate	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retention Rate	Retention rate was determined by the percentage of participants who completed all study visits.	Week 8
Overall Medication Adherence	Overall medication adherence was calculated as a percentage based on the number of pills prescribed during the study, corrected for the number of pills returned, divided by the period (in days), and multiplied by 100. An aggregate percentage of pills was calculated and reported for all seven study participants.	Upon conclusion of SCC+Varenicline treatment (4 weeks or 8 weeks based on randomization to arm/group)
Number of Participants With Treatment-Emergent Adverse Events: Upset Stomach	The number of participants with a self-reported adverse event of upset stomach was determined using a structured questionnaire of common varenicline symptoms	Upon conclusion of SCC+VT treatment (4 weeks or 8 weeks based on randomization to arm/group)
Number of Participants With Treatment-Emergent Symptoms of Major Depressive Disorder	The number of participants with self-reported Treatment-Emergent symptoms of major depressive disorder was determined using the MINI International Neuropsychiatric Interview (M.I.N.I), a short structured diagnostic interview tool used to assess DSM-IV and ICD-10 psychiatric disorders	Upon conclusion of SCC+VT treatment (4 weeks or 8 weeks based on randomization to arm/group)
Cannabis Craving	Cannabis craving was assessed using the Marijuana Craving Questionnaire-Short Form (MCQ-SF). The MCQ-SF is a valid and reliable, self-report instrument with 12 items rated on a 7-point Likert scale from 1 (strongly disagree) to 7 (strongly agree). The 12 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). Scores from the four subscales are summed with total possible scores ranging from 12 - 84. Higher scores are indicative of increased craving.	Week 4 and Week 8
Cannabis Withdrawal	Cannabis withdrawal was measured by the 15-item version of the Marijuana Withdrawal Checklist (MWC). Participants rated 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 was obtained by summing the responses. Possible total scoring ranges from 0 - 45, with 0 signifying no withdrawal symptoms and 45 signifying the most severe withdrawal symptoms.	Week 4 and Week 8
Quantity of Cannabis Use	The quantity of cannabis use over the prior 14-day period was measured using the Timeline Follow-Back (TLFB) method. TLFS is a method in which participants used a physical calendar to quantify the number of days over a specified period of time (in this study 14 days) during which cannabis was used. An aggregate value for percentage of days of cannabis use was calculated by tabulating the total number of days cannabis was used by all study participants over the prior 14-day period and dividing by the total number of calendar days over this period across the 7 participants (i.e., 14x7=98).	Week 4 and Week 8
Frequency of Cannabis Use	The frequency of cannabis use per day was evaluated over the prior 14-day period using the Timeline Follow-Back method (TLFB), a method in which participants used a physical calendar to self-report the number times per days cannabis was used.	Week 4 and Week 8
Number of Cigarettes Smoked Per Day	The number of cigarettes smoked per day was measured using Timeline Follow-Back (TLFB). TLFB is a method in which participants used a physical calendar to self-report the number of cigarettes smoked per day over the prior 14-day period in order to evaluate ongoing tobacco usage.	Week 4 and Week 8
Number of Participants With Toxicology-verified Cannabis Abstinence	The number of participants with Toxicology-verified cannabis abstinence was determined by applying the TLFB method and then biochemically confirming the number of participants with a urine tetrahydrocannabinol (THC) levels less than 50 ng/ml.	Week 4 and Week 8
Number of Participants With Biochemically-verified Tobacco Abstinence	The number of participants with biochemically-verified tobacco abstinence was determined by applying the TLFB method and then biochemically verified by measuring participant levels of expired carbon monoxide < 8 parts per million (CO < 8ppm). The Bedfont Smokerlyzer carbon monoxide monitor was used in the analysis.	Week 4 and Week 8
Mean Expired Carbon Monoxide	Mean expired carbon monoxide (CO) per participant was measured using the Bedfont Smokerlyzer carbon monoxide monitor. Results reported in mean parts per million (ppm)	Week 4 and Week 8
Number of Participants With Treatment-Emergent Suicidal Ideation Events	The number of participants with treatment-emergent suicidal ideation events was determined using the Columbia Suicide Severity Rating Scale (C-SSRS). The C-SSRS 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 as well as during the 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 final three questions indicates high-risk.	Week 4 and Week 8

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Institute on Drug Abuse (NIDA); National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Shadi Nahvi, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: April 28, 2016
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: August 30, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Marijuana Abuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 2010-279-12; K23DA025736 (U.S. NIH Grant/Contract); R25GM104547 (U.S. NIH Grant/Contract); R25DA023021 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• product manufactured in and exported from the U.S.: Yes