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.

The number of participants with a self-reported adverse event of upset stomach was determined using a structured questionnaire of common varenicline symptoms

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

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.

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.

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).

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.

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.

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.

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.

Mean expired carbon monoxide (CO) per participant was measured using the Bedfont Smokerlyzer carbon monoxide monitor. Results reported in mean parts per million (ppm)

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.

Cannabis craving was assessed using the Marijuana Craving Questionnaire-Short Form (MCQ-SF) a self-reporting tool 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.

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.

The quantity of cannabis use was measured using the Timeline Follow-Back (TLFB) method. TLFB is a method in which participants use 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 for all study participants by tabulating the total number of days cannabis was actually used by all study participants over the prior 14-day period and dividing by the total number of calendar days over the period for the 7 participants (i.e., 14x7=98).

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.

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.

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.

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.

Mean expired carbon monoxide (CO) per participant was measured using the Bedfont Smokerlyzer carbon monoxide monitor. Results reported in mean parts per million (ppm)

Retention rate was determined by the percentage of participants who completed all study visits.

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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.

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

The number of participants with a self-reported adverse event of upset stomach was determined using a structured questionnaire of common varenicline symptoms

While receiving standard clinical care without Varenicline participants were not assessed for Varenicline associated adverse effects. In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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

While receiving standard clinical care without Varenicline participants were not assessed for Varenicline associated adverse effects. In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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.

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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.

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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).

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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.

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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.

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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.

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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.

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

Mean expired carbon monoxide (CO) per participant was measured using the Bedfont Smokerlyzer carbon monoxide monitor. Results reported in mean parts per million (ppm)

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

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.

In a deviation from the trial design, one participant completed SCC alone for two weeks, then SCC+VT for four weeks, followed by SCC alone for two weeks.

Participants received four weeks of standard clinical care (SCC) plus varenicline treatment (SCC and VT). SCC included individual counseling, at least once a month, that used motivational and cognitive behavioral strategies, addressed cannabis or tobacco use, as needed, and was delivered by trained substance use disorder treatment counselors; and medications for opioid use disorder (MOUD).Varenicline treatment included a four-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.