Investigation of Kava Effects on NNK Metabolism

Investigation of Kava Effects on the Metabolism of the Tobacco-specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Humans

This is a non-therapeutic, single-arm pilot clinical trial in adult healthy smokers to assess whether kava can alter NNK metabolism in humans.

Inclusion Criteria:

• Adult ≥ 18 years

• Current smoker of ≥ 5 cigarettes daily, determined by self-report

• Adequate liver and kidney function, defined as:

  • Bilirubin, alkaline phosphatase, ALT, and AST within normal limits
  • Creatinine <1.2

• Adequate hemoglobin, defined as a hemoglobin ≥12 mg/dL for men and ≥11 for women.

• Ability and willingness to abstain from all medication and dietary supplements for 3 days prior to kava administration, continuing until a minimum of 7 days after kava administration. Topical medications and inhaled medications that do not contain steroids are permitted.

• Ability and willingness to completely abstain from alcohol consumption for 3 days prior to kava administration, continuing until a minimum of 7 days after kava administration

• Ability to understand the investigational nature of the study and provide informed consent

• Willingness to take kava supplement as instructed

Exclusion Criteria:

• Known hepatobiliary disease or impairment
• History of gastric bypass surgery, gastric banding, bowel resection, malabsorption syndromes such as celiac sprue or pancreatic insufficiency, or other conditions that may affect the absorption of kava
• Chronic medication use that cannot be safely stopped
• Use of tobacco products other than cigarettes (i.e. snuff, snuz, smokeless tobacco, cigars, pipes)
• Major or chronic medical medical disease, including heart disease, poorly controlled diabetes, etc., to be adjudicated by the principal investigator
• Women who are pregnant, intend to become pregnant within 3 months of the study period, or who are breastfeeding
• Current or recent (within 12 months) problems with drug use or alcohol dependence by self-report
• Antibiotic use within 2 months of study enrollment by self-report
• Alcohol dependence, abuse, or history of dependence/abuse by self-report