Oral Fluid, Plasma and Whole Pharmacokinetics and Stability Following Smoked Cannabis

July 3, 2018 updated by: National Institute on Drug Abuse (NIDA)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • National Institute on Drug Abuse, Biomedical Research Center (BRC)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

    1. 18 to 45 years of age;
    2. Cannabis use with a minimum frequency of at least twice per month during the three months prior to study entry for Part A or average frequency of cannabis smoking of less than twice per week (occasional cannabis smoker) in the past 3 months or at least four times per week (chronic frequent cannabis smoker) in the past 3 months for Part B;
    3. A positive urine cannabinoid screen if in the chronic frequent cannabis smoker group;
    4. Peripheral veins suitable for repeated venipuncture and/or placement of an intravenous catheter;
    5. Blood pressure (BP) and heart rate (HR) at or below the following values while sitting after five min rest: Systolic BP (SBP) 140 mm Hg, diastolic BP (DBP) 90 mm Hg, heart rate (HR) 100 bpm;
    6. ECG and three-minute rhythm strip without clinically relevant abnormalities;

EXCLUSION CRITERIA:

  1. History or presence of any clinically significant illness, as detected by history, physical examination, and/or laboratory tests, that might put the subject at increased risk of adverse events;
  2. History of a clinically significant adverse event associated with cannabis intoxication;
  3. Donation of more than 450 mL of blood within 30 days of study drug administration;
  4. If female, pregnant or nursing;
  5. Currently interested in or participating in drug abuse treatment, or participated in drug abuse treatment within 60 days preceding study enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
THC and metabolite concentrations in whole blood, plasma, and oral fluid, stability of these concentrations over time, performance on neurocognitive tasks and subjective assessments.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Marilyn Huestis, Ph.D., National Institute on Drug Abuse (NIDA)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 22, 2010

Study Completion (Actual)

November 29, 2013

Study Registration Dates

First Submitted

February 18, 2010

First Submitted That Met QC Criteria

February 18, 2010

First Posted (Estimate)

February 19, 2010

Study Record Updates

Last Update Posted (Actual)

July 5, 2018

Last Update Submitted That Met QC Criteria

July 3, 2018

Last Verified

November 29, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 999910458
  • 10-DA-N458

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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