Oral Fluid, Plasma and Whole Pharmacokinetics and Stability Following Smoked Cannabis
Condition: Cannabis Use; Drug Abuse
MeSH terms: Marijuana Abuse; Substance-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Little research has been done on how different components of cannabis (marijuana) appear in
      oral fluid (i.e., saliva) after smoking. Cannabinoids have been well studied in whole blood,
      plasma, and urine after cannabis use, but less is known about how cannabinoids appear in oral
      fluid after controlled drug administration and how long these biomarkers last after use. In
      addition, the issue of stability of cannabinoids and their glucuronide metabolites is a
      controversial topic that is poorly understood. These data are critical to the interpretation
      of cannabinoid test results.

      Objectives:

        -  To collect whole blood, plasma, urine, and oral fluid specimens after smoking cannabis,
           to characterize the disposition and pharmacokinetics of cannabinoids in multiple
           biological matrices and to provide scientifically reliable data on the stability of
           cannabinoids and metabolites.

        -  To test basic brain function and thinking processes after smoking cannabis.

      Eligibility:

      - Healthy volunteers between 18 and 45 years of age who use cannabis (an average of at least
      twice per month in the 3 months before the study.)

      Design:

        -  Participants may complete the single study session as outpatients, or they may spend the
           night prior to and/or following drug administration at the residential research unit in
           Baltimore, MD. Participants must provide a negative urine drug screen if they have not
           spent the evening prior to testing at the research unit.

        -  Participants will provide whole blood, plasma, oral fluid, and urine samples, and will
           complete several tests of thinking and brain function at the start of the study.

        -  Participants will smoke one standardized cannabis cigarette. Blood and oral fluid
           samples will be collected, and participants will repeat the tests of thinking and brain
           function multiple times after smoking.

        -  Six hours after smoking the cigarette, participants must pass a neuromotor exam (testing
           balance and coordination) before they can be discharged from the study. Participants may
           be asked to stay overnight at the clinical center if there are concerns for their safety
           because of intoxication.
    

Detailed description: 
      Background: Smoking is the most common route of cannabis administration, yet the
      pharmacokinetic properties of cannabinoids in oral fluid following cannabis smoking have not
      been adequately characterized. Characterization of cannabinoid pharmacokinetics in oral
      fluid, correlations between concentrations in different matrices and relationships between
      biomarker concentrations and concurrent pharmacodynamic effects are critical for the
      appropriate interpretation of cannabinoid tests. Furthermore, the short- and long-term
      stability of cannabinoid biomarkers, including glucuronide conjugates, in authentic whole
      blood, plasma, and oral fluid specimens following cannabis smoking is poorly defined. The
      only stability data available are from fortified samples, rather than authentic specimens.

      Objectives: Part A: (1) Characterize cannabinoid ( -9-tetrahydrocannabinol, [THC];
      11-hydroxy-THC, [11-OH-THC]; 11-nor-9-carboxy-THC, [THCCOOH]; and their Phase II conjugates)
      pharmacokinetics in whole blood, plasma, oral fluid and urine following a single smoked dose
      of cannabis. (2) Determine inter-matrix cannabinoid ratios in authentic specimens following
      controlled smoked cannabis (3) Correlate cannabinoid concentrations in whole blood, plasma
      and oral fluid with impairment and risk-taking behavior as determined through subjective
      assessments, risk-behavior trait assessments and neurocognitive tasks. (4) Determine
      stability over time of free and conjugated cannabinoids in authentic whole blood, plasma, and
      oral fluid from cannabis users following a single smoked dose of cannabis under various
      storage conditions. (5) Characterize the sensitivity, specificity, efficiency and duration of
      detection of cannabinoids with the Draeger DrugTest 5000 after a single smoked dose of
      cannabis.

      Part B: Characterize cannabinoid pharmacokinetics in whole blood, plasma, oral fluid, breath,
      and urine following a single smoked dose of cannabis. (2) Characterize the sensitivity,
      specificity, accuracy and length of detection of cannabinoids with the Draeger DrugTest 5000
      after a single smoked dosed of cannabis. (3) Determine inter-matrix cannabinoid ratios in
      authentic specimens following controlled smoked cannabis. (4) Correlate cannabinoid
      concentrations in whole blood, plasma, breath, and oral fluid with impairment as determined
      through subjective assessments and neurocognitive tasks. (5) Determine stability over time of
      free and conjugated cannabinoids in urine from cannabis users following a single smoked dose
      of cannabis under various storage conditions.

      Subject Population: Up to 50 healthy cannabis users aged 18-45 will be recruited for the
      study. In Part A, 10 completers with an average frequency of use of at least twice per month
      in the three months prior to study are required. In Part B, 10 occasional cannabis smokers
      with an average frequency of less than twice per week in the past three months and 10 chronic
      frequent cannabis smokers with an average frequency at least four times per week in the past
      three months are required.

      Experimental Design and Methods: In parts A and B, participants smoke one standardized NIDA
      THC cigarette during a single visit. Serial blood and oral fluid collections (part A and B)
      and breath collections (part B only), and assessment of neurocognitive, physiological and
      subjective effects are performed once prior to and multiple times after smoking.

      Outcome Measures: Primary outcome measures for part A include cannabinoid concentrations in
      whole blood, plasma, and oral fluid, stability of these concentrations over time, performance
      on neurocognitive tasks, and subjective assessments. Primary outcome measures for part B
      include cannabinoid concentrations in whole blood, plasma, breath, and oral fluid, evaluation
      of the DrugTest 5000 and correlation of cannabinoid breath concentration with performance on
      neurocognitive tasks and subjective assessments. An outcome measure for subsequent occasional
      smoker participants after the 9th completer is stability over time of cannabinoid
      concentrations in whole blood and plasma collected in gray-top Vacutainer tubes containing
      sodium fluoride and potassium oxalate.

      Benefits: There is no direct benefit to participants, but the study is likely to yield
      generalizable knowledge regarding cannabinoid pharmacokinetics, and pharmacodynamics for both
      Part A and Part B.

      Risks: Participation in this study represents more than minimal risk for both Part A and Part
      B because of the administration of smoked cannabis.
    

Intervention name(s): Cannabis Cigarette
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Cannabinoids; Oral Fluid; Pharmacokinetics; Stability; Smoked Cannabis