THCV Treatment for Smokers

Development of Tetrahydrocannabivarin as a Treatment for Smokers

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Smoking Cessation; Tobacco Use Disorder
• Intervention / Treatment: Drug: Δ9-Tetrahydrocannabivarin (oral gummy); Drug: Matched Placebo (oral gummy)

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.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jessica Jenkins, MS; Phone Number: 310-206-6756; Email: jenkinsj@ucla.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Δ9-THCV first, then placebo.; Participants will first take a 10mg Δ9-THCV gummy once a day for 5 days. After a 14-day washout period, participants will take a matched placebo gummy (0mg Δ9-THCV) once a day for 5 days.	Drug: Δ9-Tetrahydrocannabivarin (oral gummy); 10mg Δ9-Tetrahydrocannabivarin oral gummy; Drug: Matched Placebo (oral gummy); Matched Placebo (oral gummy, 0mg Δ9-Tetrahydrocannabivarin)
Experimental: Placebo first, then THCV; Participants will take a placebo gummy (0mg Δ9-THCV) once a day for 5 days. After a 14-day washout period, participants will take a 10mg Δ9-THCV gummy once a day for 5 days.	Drug: Δ9-Tetrahydrocannabivarin (oral gummy); 10mg Δ9-Tetrahydrocannabivarin oral gummy; Drug: Matched Placebo (oral gummy); Matched Placebo (oral gummy, 0mg Δ9-Tetrahydrocannabivarin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Latency to initiate smoking	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).	Assessed during each 5-day medication condition, following overnight abstinence on Day 5
Number of cigarettes smoked during self-administration	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).	Assessed during each 5-day medication condition, following overnight abstinence on Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Questionnaire of Smoking Urges-Brief total score	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.	Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence
Minnesota Nicotine Withdrawal Scale score	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.	Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence
Modified Cigarette Evaluation Questionnaire satisfaction score	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.	Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence.
Modified Cigarette Evaluation Questionnaire psychological reward score	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.	Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence.
Modified Cigarette Evaluation Questionnaire nausea/dizziness score	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.	Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence.
Modified Cigarette Evaluation Questionnaire craving relief score	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.	Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence.
Modified Cigarette Evaluation Questionnaire enjoyment of airway sensations score	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.	Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence.

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Lara A Ray, PhD, University of California, Los Angeles; Principal Investigator: Erica N Grodin, PhD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: May 26, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: smoking cessation; tobacco use disorder; cigarette smoking; THCV; Tetrahydrocannabivarin
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Behavior; Smoking; Health Behavior; Tobacco Smoking; Tobacco Use; Tobacco Use Disorder; Smoking Cessation; Cigarette Smoking
• Other Study ID Numbers: IRB-26-1097; R21DA059769 (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
• Studies a U.S. FDA-regulated device product: No