Smoking Cessation, Tobacco Use Disorder
Conditions
Keywords
smoking cessation, tobacco use disorder, cigarette smoking, THCV, Tetrahydrocannabivarin
Brief summary
This study will randomize 32 non-treatment-seeking individuals who smoke cigarettes daily into a randomized, crossover, double-blind, placebo-controlled study testing the safety, tolerability, and initial efficacy of Δ9-tetrahydrocannabivarin (Δ9-THCV).
Detailed description
The objective of this study is to examine the safety, tolerability, and initial efficacy of Δ9-tetrahydrocannabivarin (Δ9-THCV) in daily smokers. We will randomize 32 non-treatment-seeking adults who smoke cigarettes daily (50% female) into a randomized, double-blind, placebo-controlled, counter-balanced, within-subject human laboratory study of Δ9-THCV (10 mg oral) and matched placebo. Specifically, participants will complete two 5-day outpatient medication periods, with a 14-day washout period in between, during which they will receive either Δ9-THCV or placebo in a counter-balanced order, such that all participants will complete both medication conditions across the study. Following each 5-day medication period, participants will complete a laboratory study visit during which they will undergo the McKee Smoking Lapse Task to assess the ability to resist smoking, cigarette self-administration, craving, withdrawal, and subjective effects of nicotine. Total study participation will be approximately 4 weeks.
Interventions
DRUGΔ9-Tetrahydrocannabivarin (oral gummy)
10mg Δ9-Tetrahydrocannabivarin oral gummy
DRUGMatched Placebo (oral gummy)
Matched Placebo (oral gummy, 0mg Δ9-Tetrahydrocannabivarin)
Sponsors
University of California, Los Angeles
National Institute on Drug Abuse (NIDA)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
This study uses a randomized, double-blind, placebo-controlled crossover design in which participants receive both Δ9-THCV (10mg) and a matched placebo across two separate 5-day outpatient medication conditions. Treatment order will be counter-balanced across participants, and the medication conditions will be separated by a 14-day washout period.
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Be between the ages of 21 and 65; 2. Smoke 10 or more combustible cigarettes per day; 3. Have fewer than 3 months of smoking abstinence in the past year; 4. Has self-reported ≥10 lifetime uses of cannabis products; 5. Have self-reported recent (past 3-month) use of cannabis products; 6. Agree to abstain from all other cannabinoid use during the study; 7. Agree to abstain from all other medication use during the study, other than methods of birth control as listed in inclusion criteria for female participants; 8. Agree to one of the following methods of birth control (if female), unless she or partner are surgically sterile: oral contraceptives, Contraceptive sponge, patch, double barrier, intrauterine contraceptive device, etonogestrel implant, medroxyprogesterone acetate contraceptive injection, hormonal vaginal contraceptive ring, complete abstinence from sexual intercourse.
Exclusion criteria
1. Have current (last 12 months) DSM-5 diagnosis of substance use disorder for any psychoactive substances other than nicotine; 2. Have a lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any other psychotic disorder; 3. Have a score of 3 or greater on the Columbia Suicide Severity Rating Scale (C-SSRS) at screening or anytime during study participation; 4. Have a positive urine screen for any substances, including cannabis 5. Have a breathalyzer reading above 0.000 g/dl; 6. Be pregnant, nursing, or planning to become pregnant while taking part in the study; 7. Have a medical condition that may interfere with safe study participation; 8. Have clinically significant abnormalities on the EKG; 9. Have evidence of renal impairment, defined by an eGFR value of \<90 ml/min; 10. Have evidence of hepatic impairment, defined by a score of ≥5 points on the Child-Pugh assessment of liver function; 11. Exceed Grade 2 laboratory or vital sign abnormalities, based on FDA Guidance Document "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; 12. Have past month use of cannabis or cannabis products; 13. Have past month use of electronic nicotine delivery system (ENDS); 14. Have use of any medications (other than methods of birth control as listed in inclusion criteria for female participants) within 14 days or 5 half-lives (whichever is longer) prior to study drug administration, and throughout the study, including medication for smoking cessation, any prescription, OTC, dietary supplements, herbal products, or vitamins; 15. Have any other circumstances that, in the opinion of the investigators, would not be a good fit for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Latency to initiate smoking | Assessed during each 5-day medication condition, following overnight abstinence on Day 5 | Participants will complete the McKee Smoking Lapse Task following overnight abstinence to assess the effects of oral Δ9-THCV (10 mg), compared with placebo, on the ability to resist smoking. The primary outcome is latency to initiate smoking during the 50-minute delay period, defined as the number of minutes participants delay smoking their first cigarette (range: 0-50 minutes). |
| Number of cigarettes smoked during self-administration | Assessed during each 5-day medication condition, following overnight abstinence on Day 5 | Participants will complete the McKee Smoking Lapse Task following overnight abstinence to assess the effects of oral Δ9-THCV (10 mg), compared with placebo, on cigarette self-administration. The outcome is the number of cigarettes smoked during the 60-minute self-administration period of the task (no set range). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Questionnaire of Smoking Urges-Brief total score | Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence | Participants will complete the 10-item Questionnaire of Smoking Urges-Brief (QSU-Brief) during the McKee Smoking Lapse Task to assess cigarette craving. The QSU-Brief assesses urges and cravings using a 7-point Likert response scale, with higher scores indicating greater craving (range: 10-70). Cue-induced cigarette craving in response to cigarette (vs. neutral) cues will be calculated and compared between the Δ9-THCV and placebo conditions. |
| Minnesota Nicotine Withdrawal Scale score | Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence | Participants will complete ratings of nicotine withdrawal following overnight abstinence using the 8-item Minnesota Nicotine Withdrawal Scale (MNWS), with higher values indicating more severe withdrawal (range: 0-32). Differences in MNWS scores will be evaluated between the Δ9-THCV and placebo conditions. |
| Modified Cigarette Evaluation Questionnaire satisfaction score | Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence. | Participants will complete the 12-item Modified Cigarette Evaluation Questionnaire (mCEQ) during the cigarette self-administration period of the McKee Smoking Lapse Task to assess satisfaction associated with smoking. Items are rated on a 7-point scale, with higher scores indicating greater endorsement. The satisfaction subscale score is calculated as the sum of Items 1, 2, and 12 (range: 3-21). Differences in satisfaction scores will be evaluated between the Δ9-THCV and placebo conditions. |
| Modified Cigarette Evaluation Questionnaire psychological reward score | Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence. | Participants will complete the 12-item Modified Cigarette Evaluation Questionnaire (mCEQ) during the cigarette self-administration period of the McKee Smoking Lapse Task to assess psychological reward associated with smoking. Items are rated on a 7-point scale, with higher scores indicating greater endorsement. The psychological reward subscale score is calculated as the sum of Items 4, 5, 6, 7, 8 (range: 5-35). Differences in psychological reward scores will be evaluated between the Δ9-THCV and placebo conditions. |
| Modified Cigarette Evaluation Questionnaire nausea/dizziness score | Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence. | Participants will complete the 12-item Modified Cigarette Evaluation Questionnaire (mCEQ) during the cigarette self-administration period of the McKee Smoking Lapse Task to assess nausea and dizziness associated with smoking. Items are rated on a 7-point scale, with higher scores indicating greater endorsement. The nausea/dizziness subscale score is calculated as the sum of Items 9 and 10 (range: 2-14). Differences in nausea/dizziness scores will be evaluated between the Δ9-THCV and placebo conditions. |
| Modified Cigarette Evaluation Questionnaire craving relief score | Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence. | Participants will complete the 12-item Modified Cigarette Evaluation Questionnaire (mCEQ) during the cigarette self-administration period of the McKee Smoking Lapse Task to assess craving relief associated with smoking. Items are rated on a 7-point scale, with higher scores indicating greater endorsement. The craving relief subscale score is based on Item 11 (range: 1-7). Differences in craving relief scores will be evaluated between the Δ9-THCV and placebo conditions. |
| Modified Cigarette Evaluation Questionnaire enjoyment of airway sensations score | Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence. | Participants will complete the 12-item Modified Cigarette Evaluation Questionnaire (mCEQ) during the cigarette self-administration period of the McKee Smoking Lapse Task to assess the enjoyment of airway sensations associated with smoking. Items are rated on a 7-point scale, with higher scores indicating greater endorsement. The enjoyment of airway sensations subscale score is based on Item 3 (range: 1-7). Differences in enjoyment of airway sensations scores will be evaluated between the Δ9-THCV and placebo conditions. |
Contacts
CONTACTJessica Jenkins, MS
PRINCIPAL_INVESTIGATORLara A Ray, PhD
University of California, Los Angeles
PRINCIPAL_INVESTIGATORErica N Grodin, PhD
University of California, Los Angeles
Outcome results
None listed