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

Official Title: “Oral Fluid, Plasma and Whole Pharmacokinetics and Stability Following Smoked Cannabis”

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.

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. Oral fluid is an important alternative matrix for monitoring in drug treatment, criminal justice, military and workplace settings, and for driving under the influence of drugs detection. Characterization of cannabinoid pharmacokinetics in oral fluid, correlations between oral fluid, whole blood and plasma concentrations, and relationships between biomarker concentrations and concurrent pharmacodynamic effects are critical for the appropriate interpretation of cannabinoid tests. Furthermore, of great practical significance, 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. Our own cannabinoid pharmacokinetic data have been questioned by reviewers due to the lack of stability data. Few investigators have the ability to conduct controlled administration studies and analyze these complex biological matrices with highly sensitive and specific instrumentation.

Objectives: (1) Characterize cannabinoid (Delta-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 whole blood/oral fluid and plasma/oral fluid cannabinoid ratios in authentic specimens following controlled smoked cannabis (3) Correlate concentrations of THC and its metabolites in whole blood, plasma and oral fluid with impairment as determined through subjective assessments and neurocognitive tasks. (4) Determine stability over time of free and conjugated cannabinoids in authentic whole blood, plasma, oral fluid and urine from cannabis users following a single smoked dose of cannabis under various storage conditions.

Subject Population:

Up to 15 healthy cannabis users aged 18-45 with an average frequency of use of at least twice per month in the three months prior to study entry will be recruited for the study.

Ten completers are required.

Experimental Design and Methods:

Participants smoke one standardized NIDA THC cigarette during a single visit. Serial blood and oral fluid collections, and assessment of neurocognitive, physiological and subjective effects are performed once prior to and multiple times after smoking.

Outcome Measures:

Primary outcome measures include THC and metabolite concentrations in whole blood, plasma, and oral fluid, stability of these concentrations over time, performance on neurocognitive tasks and subjective assessments

Intervention(s) in this Clinical Trial

• Drug: Cannabis Cigarette
  • N/A

Primary Measures

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

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;
• 3. A positive urine cannabinoid screen;
• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: National Institute on Drug Abuse (NIDA) NIH

Overall Clinical Trial Officials and Contacts

Overall Contact: MMG Recruiting (800) 535-8254 researchstudies@mail.nih.gov

Information obtained from ClinicalTrials.gov on February 02, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01071616

Study ID Number: 999910458

ClinicalTrials.gov Identifier: NCT01071616

Health Authority: United States: Federal Government