THCV Treatment for Smokers

Official title

Development of Tetrahydrocannabivarin as a Treatment for Smokers

Overview

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

• Drug Δ9-Tetrahydrocannabivarin (oral gummy)
  10mg Δ9-Tetrahydrocannabivarin oral gummy
• Drug Matched Placebo (oral gummy)
  Matched Placebo (oral gummy, 0mg Δ9-Tetrahydrocannabivarin)

Primary outcome measures

• Latency to initiate smoking [Time frame: Assessed during each 5-day medication condition, following overnight abstinence on Day 5]
• Number of cigarettes smoked during self-administration [Time frame: Assessed during each 5-day medication condition, following overnight abstinence on Day 5]

Secondary outcome measures (7)

• Questionnaire of Smoking Urges-Brief total score [Time frame: Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence]
• Minnesota Nicotine Withdrawal Scale score [Time frame: Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence]
• Modified Cigarette Evaluation Questionnaire satisfaction score [Time frame: Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence.]
• Modified Cigarette Evaluation Questionnaire psychological reward score [Time frame: Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence.]
• Modified Cigarette Evaluation Questionnaire nausea/dizziness score [Time frame: Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence.]
• Modified Cigarette Evaluation Questionnaire craving relief score [Time frame: 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 [Time frame: Assessed during each 5-day medication condition during the Day 5 laboratory session following overnight abstinence.]

Eligibility criteria

Inclusion criteria

• Be between the ages of 21 and 65;
• Smoke 10 or more combustible cigarettes per day;
• Have fewer than 3 months of smoking abstinence in the past year;
• Has self-reported ≥10 lifetime uses of cannabis products;
• Have self-reported recent (past 3-month) use of cannabis products;
• Agree to abstain from all other cannabinoid use during the study;
• 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;
• 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

• Have current (last 12 months) DSM-5 diagnosis of substance use disorder for any psychoactive substances other than nicotine;
• Have a lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any other psychotic disorder;
• Have a score of 3 or greater on the Columbia Suicide Severity Rating Scale (C-SSRS) at screening or anytime during study participation;
• Have a positive urine screen for any substances, including cannabis
• Have a breathalyzer reading above 0.000 g/dl;
• Be pregnant, nursing, or planning to become pregnant while taking part in the study;
• Have a medical condition that may interfere with safe study participation;
• Have clinically significant abnormalities on the EKG;
• Have evidence of renal impairment, defined by an eGFR value of <90 ml/min;
• Have evidence of hepatic impairment, defined by a score of ≥5 points on the Child-Pugh assessment of liver function;
• 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";
• Have past month use of cannabis or cannabis products;
• Have past month use of electronic nicotine delivery system (ENDS);
• 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;
• Have any other circumstances that, in the opinion of the investigators, would not be a good fit for study participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07636356 · IRB-26-1097 · R21DA059769

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗