- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04201197
Interactions Between Cannabinoids and Cytochrome P450-Metabolized Drugs
June 30, 2023 updated by: Johns Hopkins University
This study will evaluate drug-drug interactions between cannabis extracts containing Tetrahydrocannabinol (THC) and THC+ Cannabinoids (CBD) and probe drugs for select CYP450 pathways including: caffeine (CYP1A2), omeprazole (CYP2C19), losartan (CYP2C9), dextromethorphan (CYP2D6), and midazolam (CYP3A).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Despite the widespread use and availability of cannabis products, substantive deficiencies remain regarding the potential risks for cannabis or cannabinoids to precipitate adverse interactions with conventional drugs.
Evidence from the few systematic clinical studies that have been conducted suggests that THC and CBD can inhibit metabolism of other drugs, via interactions with cytochrome P450 (CYP) enzymes, a large family of enzymes involved in the metabolism of numerous drugs and foreign chemicals in the body.
Accordingly, evaluating the potential for drug-drug interactions between cannabis-derived products and common CYP-metabolized drugs merits further investigation.
This double-blind, randomized crossover design study will evaluate whether, and to what extent, oral administration of cannabis extracts containing high doses of CBD and/or THC alter the pharmacokinetics of 5 drugs metabolized via CYP pathways including: caffeine (CYP1A2), omeprazole (CYP2C19), losartan (CYP2C9), dextromethorphan (CYP2D6), and midazolam (CYP3A).
Healthy adults will complete three experimental dosing sessions, in which participants will orally ingest brownies containing (1) a high THC cannabis extract with a target THC dose of 40mg, (2) a high CBD cannabis extract with a target CBD dose of 1350mg + a THC dose of 40mg, or (3) placebo.
In all three experimental dosing sessions, consumption of the cannabis extract infused brownie will be followed by ingestion of a drug "cocktail" comprised of commercial formulations of therapeutic or subtherapeutic doses of each drug.
This collection of probe drugs, coined the Inje Cocktail, has been demonstrated to be safe, both administered alone and with various CYP450 inhibitors.
At baseline and following administration of the study drugs, a battery of subjective, physiological, and cognitive performance assessments will be completed and biological specimens obtained.
Each session will consist of a 12-hour outpatient drug administration visit and a 1-hour outpatient visit the subsequent day for additional biospecimen collection, cognitive testing, and subjective drug effect questionnaires.
The study will conclude when 18 participants complete all 3 experimental sessions.
The outcomes of this study will be useful to inform clinical decision-making regarding co-administration of cannabinoid-containing products with drugs that are either commonly prescribed by physicians or readily available over-the-counter.
Study Type
Interventional
Enrollment (Actual)
22
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
-
-
Maryland
-
Baltimore, Maryland, United States, 21224
- Johns Hopkins University
-
-
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
18 years to 50 years (Adult)
Accepts Healthy Volunteers
Yes
Description
Inclusion Criteria:
- Healthy adult between 18-50 years old
- BMI between 18 to 34 kg/m2
- Willing to use birth control
- Willing to abstain from all medications and citrus fruits for the duration of the study
Exclusion Criteria:
- Medical or psychiatric illness judged by the investigator to put the participant at greater risk of experiencing an adverse event due to drug exposure or completion of other study procedures.
- Use of medications which, in the opinion of the investigator or medical staff, will interfere with the study outcomes or the safety of the participant.
- Clinically significant impairment of kidney, liver, or thyroid function (serum creatinine >1.2 mg/ml (kidney), liver function tests >3x the upper limit of normal (alanine amino transferase >99 U/L; aspartate amino transferase > 99 U/L), and thyroid stimulating hormone > 4.2 uIU/ml), or evidence of current anemia based on blood chemistry testing.
- History of adverse events associated with the ingestion of cannabis or any medications in the Inje cocktail judged by the investigator to present an undue risk of harm to the participant.
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: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Inje Cocktail
Single oral administration of caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg)
|
Acute drug exposure
|
Experimental: Inje Cocktail + THC extract
Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC
|
Acute drug exposure
Acute drug exposure
|
Experimental: Inje Cocktail + THC/CBD extract
Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
|
Acute drug exposure
Acute drug exposure
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Losartan Area Under the Curve (AUC) in Plasma
Time Frame: 24 hours
|
Area under the curve concentration (h*ng/mL) of losartan in plasma using data points obtained 0, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
|
24 hours
|
Peak Change From Baseline Number of Correct Trials on Paced Auditory Serial Addition Task (PASAT)
Time Frame: 8 hours
|
Computerized version of Paced Auditory Serial Addition Task will be administered to assess working memory performance.
Reported data reflect the peak change from baseline in the total correct trials out of 90 recorded (lower scores indicate worse performance) obtained 1, 2, 3, 4, 6, or 8 hours post-dose.
|
8 hours
|
Peak Change From Baseline Cognitive Performance as Assessed by the Divided Attention Task
Time Frame: 8 hours
|
Cognitive performance will be evaluated with the Divided Attention Task.
Reported data reflect the peak change from baseline performance measured as the mean distance (in computer pixels) of the mouse cursor from the central stimulus recorded 1, 2, 3, 4, 6, or 8 hours post-dose.
Higher scores indicate worse performance.
|
8 hours
|
Drug Effect Questionnaire (DEQ) - Peak Score for Feel Drug Effect
Time Frame: 24 hours
|
The DEQ will be used to obtain subjective ratings of "feel drug effects".
Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.
Peak rating within 24 hours post-dose is reported.
|
24 hours
|
Number of Correct Trials on the Digit Symbol Substitution Task (DSST)
Time Frame: 8 hours
|
Computerized version of Digit Symbol Substitution Task will be administered to assess psychomotor performance.
Results reported reflect the peak change from baseline on the total correct trials in 90 seconds (lower scores indicate worse performance) assessed 1, 2, 3, 4, 6, or 8 hours post-dose.
|
8 hours
|
Peak Change From Baseline Beats Per Minute for Heart Rate (HR)
Time Frame: 8 hours
|
HR will be obtained using an automated monitor to evaluate changes in beats per minute as a function of conditions.
Data reflect the peak change from baseline measured 1, 2, 3, 4, 6, or 8 hours post-dose.
|
8 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Caffeine AUC in Plasma
Time Frame: 24 hours
|
Area under the curve concentration (h*ng/mL) of caffeine in plasma using data points obtained 0, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
|
24 hours
|
Omeprazole AUC in Plasma
Time Frame: 24 hours
|
Area under the curve concentration (h*ng/mL) of omeprazole in plasma using data points obtained 0, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
|
24 hours
|
Dextromethorphan AUC in Plasma
Time Frame: 24 hours
|
Area under the curve concentration (h*ng/mL) of dextromethorphan in plasma using data points obtained 0, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
|
24 hours
|
Midazolam AUC in Plasma
Time Frame: 24 hours
|
Area under the curve concentration (h*ng/mL) of midazolam in plasma using data points obtained 0, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose
|
24 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Ryan Vandrey, PhD, Johns Hopkins University
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 (Actual)
November 10, 2020
Primary Completion (Actual)
March 16, 2022
Study Completion (Actual)
July 28, 2022
Study Registration Dates
First Submitted
December 13, 2019
First Submitted That Met QC Criteria
December 13, 2019
First Posted (Actual)
December 17, 2019
Study Record Updates
Last Update Posted (Estimated)
July 24, 2023
Last Update Submitted That Met QC Criteria
June 30, 2023
Last Verified
June 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Psychotropic Drugs
- Hallucinogens
- Cannabinoid Receptor Agonists
- Cannabinoid Receptor Modulators
- Dronabinol
Other Study ID Numbers
- IRB00207237
- U54AT008909 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
We will share protocol information and data to other scientists with reasonable requests for data sharing.
IPD Sharing Time Frame
After publication of the primary outcomes.
Availability is indefinite.
IPD Sharing Access Criteria
Send request to PI.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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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