THCV Treatment for Smokers

University of California, Los Angeles (UCLA)

Status and phase: Begins enrollment in 1 month; Phase 2

Conditions: Tobacco Use Disorder; Smoking Cessation

Treatments: Drug: Δ9-Tetrahydrocannabivarin (oral gummy); Drug: Matched Placebo (oral gummy)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07636356

R21DA059769 (U.S. NIH Grant/Contract)

IRB-26-1097

Details and patient eligibility

About

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).

Full 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.

Enrollment: 32 estimated patients

Sex: All

Ages: 21 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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32 participants in 2 patient groups

Δ9-THCV first, then placebo.

Experimental group

Description:

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.

Treatment:

Drug: Matched Placebo (oral gummy)

Drug: Δ9-Tetrahydrocannabivarin (oral gummy)

Placebo first, then THCV

Experimental group

Description:

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.

Treatment:

Drug: Matched Placebo (oral gummy)

Drug: Δ9-Tetrahydrocannabivarin (oral gummy)