Cannabis UsePhase 1NCT01071616
Oral Fluid, Plasma and Whole Pharmacokinetics and Stability Following Smoked Cannabis
A Phase 1 study testing Cannabis Cigarette in people with Cannabis Use and Drug Abuse, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Cannabis Use, Drug Abuse
- What is being tested?
- Cannabis Cigarette
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jan 2010to 29 Nov 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 18 to 45 years of age;
- 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;
- A positive urine cannabinoid screen if in the chronic frequent cannabis smoker group;
- Peripheral veins suitable for repeated venipuncture and/or placement of an intravenous catheter;
- 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;
- ECG and three-minute rhythm strip without clinically relevant abnormalities;
Who cannot join
- 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;
- History of a clinically significant adverse event associated with cannabis intoxication;
- Donation of more than 450 mL of blood within 30 days of study drug administration;
- If female, pregnant or nursing;
- Currently interested in or participating in drug abuse treatment, or participated in drug abuse treatment within 60 days preceding study enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute on Drug Abuse, Biomedical Research Center (BRC)
Baltimore, Maryland, 21224
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Cannabis Use, Drug Abuse
- Being tested
- Cannabis Cigarette
- Keywords
- Cannabinoids, Oral Fluid, Pharmacokinetics, Stability, Smoked Cannabis
- Medical subject headings
- Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cannabis CigaretteDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
THC and metabolite concentrations in whole blood, plasma, and oral fluid, stability of these concentrations over time, performance on neurocognitive tasks and subjective assessments.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2010 (estimated)
- Study start22 Jan 2010
- Study completion29 Nov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cannabis UseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Marilyn Huestis, Ph.D., Principal investigator, National Institute on Drug Abuse (NIDA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01071616
- Sponsor's protocol ID
- 999910458
- Other IDs
- 10-DA-N458
- Status last verified
- 29 Nov 2013
- First submitted
- 18 Feb 2010
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Vega WA, Aguilar-Gaxiola S, Andrade L, Bijl R, Borges G, Caraveo-Anduaga JJ, DeWit DJ, Heeringa SG, Kessler RC, Kolody B, Merikangas KR, Molnar BE, Walters EE, Warner LA, Wittchen HU. Prevalence and age of onset for drug use in seven international sites: results from the international consortium of psychiatric epidemiology. Drug Alcohol Depend. 2002 Dec 1;68(3):285-97. doi: 10.1016/s0376-8716(02)00224-7.
PubMed 12393223Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Frank RA. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry. 2001 Apr;58(4):322-8. doi: 10.1001/archpsyc.58.4.322.
PubMed 11296091Huestis MA. Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol. 2005;(168):657-90. doi: 10.1007/3-540-26573-2_23.
PubMed 16596792
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Fluid, Plasma and Whole Pharmacokinetics and Stability Following Smoked Cannabis
- ClinicalTrials.gov ID
- NCT01071616
- Acronym / sponsor ID
- 999910458
- Conditions
- Cannabis Use, Drug Abuse
- Keywords
- Cannabinoids, Oral Fluid, Pharmacokinetics, Stability, Smoked Cannabis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- 22 Jan 2010
- Study completion
- 29 Nov 2013 (actual)
- First posted
- 19 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
Key exclusion criteria (5 listed)
- 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;
- History of a clinically significant adverse event associated with cannabis intoxication;
- Donation of more than 450 mL of blood within 30 days of study drug administration;
- If female, pregnant or nursing;
- Currently interested in or participating in drug abuse treatment, or participated in drug abuse treatment within 60 days preceding study enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cannabis Cigarette | Drug | – |
Primary outcome
THC and metabolite concentrations in whole blood, plasma, and oral fluid, stability of these concentrations over time, performance on neurocognitive tasks and subjective assessments.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 12393223Vega WA, Aguilar-Gaxiola S, Andrade L, Bijl R, Borges G, Caraveo-Anduaga JJ, DeWit DJ, Heeringa SG, Kessler RC, Kolody B, Merikangas KR, Molnar BE, Walters EE, Warner LA, Wittchen HU. Prevalence and age of onset for drug use in seven international sites: results from the international consortium of psychiatric epidemiology. Drug Alcohol Depend. 2002 Dec 1;68(3):285-97. doi: 10.1016/s0376-8716(02)00224-7.
- Background: PubMed 11296091Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Frank RA. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry. 2001 Apr;58(4):322-8. doi: 10.1001/archpsyc.58.4.322.
- Background: PubMed 16596792Huestis MA. Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol. 2005;(168):657-90. doi: 10.1007/3-540-26573-2_23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marilyn Huestis, Ph.D. principal investigator
National Institute on Drug Abuse (NIDA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cannabis Cigarette in people with Cannabis Use and Drug Abuse, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01071616, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018.