Drug-InteractionsPhase 1NCT04201197
Interactions Between Cannabinoids and Cytochrome P450-Metabolized Drugs
A Phase 1 study testing Inje cocktail, THC Cannabis extract and THC/CBD Cannabis Extract in people with Drug-Interactions, run by Johns Hopkins University at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug-Interactions
- What is being tested?
- Inje cocktail, THC Cannabis extract and THC/CBD Cannabis Extract
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Nov 2020to 28 Jul 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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).
Read the 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.
- Conditions
- Drug-Interactions
- Being tested
- Inje cocktail, THC Cannabis extract, THC/CBD Cannabis Extract
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inje cocktailDrug
Acute drug exposure
THC Cannabis extractDrug
Acute drug exposure
THC/CBD Cannabis ExtractDrug
Acute drug exposure
| Study group | Role | What they receive |
|---|---|---|
| Inje Cocktail | Active comparator | Single oral administration of caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) Receives: Drug: Inje cocktail |
| Inje Cocktail + THC extract | Experimental | Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC Receives: Drug: Inje cocktail; Drug: THC Cannabis extract |
| Inje Cocktail + THC/CBD extract | Experimental | Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD Receives: Drug: Inje cocktail; Drug: THC/CBD Cannabis Extract |
What is being measured
The primary outcome is the main question the study is designed to answer.
Losartan Area Under the Curve (AUC) in Plasma
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
Measured: 24 hours
Peak Change From Baseline Number of Correct Trials on Paced Auditory Serial Addition Task (PASAT)
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.
Measured: 8 hours
Peak Change From Baseline Cognitive Performance as Assessed by the Divided Attention Task
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.
Measured: 8 hours
Drug Effect Questionnaire (DEQ) - Peak Score for Feel Drug Effect
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.
Measured: 24 hours
Number of Correct Trials on the Digit Symbol Substitution Task (DSST)
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.
Measured: 8 hours
Peak Change From Baseline Beats Per Minute for Heart Rate (HR)
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.
Measured: 8 hours
Secondary outcomes (4)
Caffeine AUC in Plasma
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
Measured: 24 hours
Omeprazole AUC in Plasma
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
Measured: 24 hours
Dextromethorphan AUC in Plasma
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
Measured: 24 hours
Midazolam AUC in Plasma
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
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2019
- Study start10 Nov 2020
- Primary completion16 Mar 2022
- Study completion28 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug-InteractionsStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Washington State University, National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Sponsor
- Investigators
- Ryan Vandrey, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04201197
- Sponsor's protocol ID
- IRB00207237
- Other IDs
- U54AT008909
- Status last verified
- Jun 2023
- First submitted
- 13 Dec 2019
- Last updated
- 24 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will share protocol information and data to other scientists with reasonable requests for data sharing.
Publications
Zamarripa CA, Spindle TR, Surujunarain R, Weerts EM, Bansal S, Unadkat JD, Paine MF, Vandrey R. Assessment of Orally Administered Delta9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Delta9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial. JAMA Netw Open. 2023 Feb 1;6(2):e2254752. doi: 10.1001/jamanetworkopen.2022.54752.
PubMed 36780161
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interactions Between Cannabinoids and Cytochrome P450-Metabolized Drugs
- ClinicalTrials.gov ID
- NCT04201197
- Acronym / sponsor ID
- IRB00207237
- Conditions
- Drug-Interactions
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Washington State University, National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 10 Nov 2020 (actual)
- Primary completion
- 16 Mar 2022 (actual)
- Study completion
- 28 Jul 2022 (actual)
- First posted
- 17 Dec 2019 (actual)
- Results
- Posted 24 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Inje Cocktail | Active comparator | Drug: Inje cocktailSingle oral administration of caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) |
| Inje Cocktail + THC extract | Experimental | Drug: Inje cocktail, Drug: THC Cannabis extractSingle oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC |
| Inje Cocktail + THC/CBD extract | Experimental | Drug: Inje cocktail, Drug: THC/CBD Cannabis ExtractSingle oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
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 |
|---|---|---|
| Inje cocktailAcute drug exposure | Drug | Inje Cocktail, Inje Cocktail + THC extract, Inje Cocktail + THC/CBD extract |
| THC Cannabis extractAcute drug exposure | Drug | Inje Cocktail + THC extract |
| THC/CBD Cannabis ExtractAcute drug exposure | Drug | Inje Cocktail + THC/CBD extract |
Primary outcome
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
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.
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.
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.
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.
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.
4 secondary outcomes
Caffeine AUC in Plasma
Time frame: 24 hours
Omeprazole AUC in Plasma
Time frame: 24 hours
Dextromethorphan AUC in Plasma
Time frame: 24 hours
Midazolam AUC in Plasma
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36780161Zamarripa CA, Spindle TR, Surujunarain R, Weerts EM, Bansal S, Unadkat JD, Paine MF, Vandrey R. Assessment of Orally Administered Delta9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Delta9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial. JAMA Netw Open. 2023 Feb 1;6(2):e2254752. doi: 10.1001/jamanetworkopen.2022.54752.
- Individual participant dataSharing planned: Yes. We will share protocol information and data to other scientists with reasonable requests for data sharing.
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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.
Ryan Vandrey, PhD principal investigator
Johns Hopkins University
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 Inje cocktail, THC Cannabis extract and THC/CBD Cannabis Extract in people with Drug-Interactions, run by Johns Hopkins University 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 4 inclusion and 4 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 24 Jul 2023. 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?
Yes. Results are posted in the registry (first posted 24 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Losartan Area Under the Curve (AUC) in Plasma (time frame: 24 hours). The study lists 6 primary outcomes in all. 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 NCT04201197, which also lists 1 linked publication.
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 24 Jul 2023.