Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| U54AT008909 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Washington State University | OTHER |
| National Center for Complementary and Integrative Health (NCCIH) | NIH |
Not provided
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Inje Cocktail | Active Comparator | Single oral administration of caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) |
|
| Inje Cocktail + THC extract | Experimental | Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC |
|
| Inje Cocktail + THC/CBD extract | Experimental | Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inje cocktail | Drug | Acute drug exposure |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 24 hours |
| Omeprazole AUC in Plasma |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ryan Vandrey, PhD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University | Baltimore | Maryland | 21224 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36780161 | Derived | 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. |
Not provided
Not provided
We will share protocol information and data to other scientists with reasonable requests for data sharing.
After publication of the primary outcomes. Availability is indefinite.
Send request to PI.
Not provided
This was a within-subjects design, so all participants were exposed to all three conditions in a randomized order.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Inje Cocktail, Inje Cocktail + THC Extract, Inje Cocktail + THC/CBD Extract | Participants ingested THC, THC/CBD, and the Inje Cocktail in a within-subject crossover design. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Evaluable Study Completers | All study completers completed the following three conditions, in a randomized order:
|
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 24 hours |
|
up to 38 days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Inje Cocktail + Placebo | Participants ingested the Inje Cocktail and a brownie containing no cannabis |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ryan Vandrey | Johns Hopkins School of Medicine | 410-550-4036 | rvandrey@jhmi.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 22, 2021 | Apr 25, 2023 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
Not provided
Placebo controlled, double blind
| THC Cannabis extract | Drug | Acute drug exposure |
|
| THC/CBD Cannabis Extract | Drug | Acute drug exposure |
|
| 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. | 8 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 | 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 | 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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 | Inje Cocktail + THC/CBD | Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD |
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | Correct trials | 8 hours |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | Computer pixels | 8 hours |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | Score on a scale | 24 hours |
|
|
|
| Primary | 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. | All participants were exposed to each of the 3 conditions | Posted | Mean | Standard Deviation | Correct trials | 8 hours |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | Beats per minute | 8 hours |
|
|
|
| Secondary | 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 | This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 24 hours |
|
|
|
| Secondary | 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 | This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 24 hours |
|
|
|
| Secondary | 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 | This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 24 hours |
|
|
|
| Secondary | 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 | This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 24 hours |
|
|
|
| 0 |
| 22 |
| 0 |
| 22 |
| 0 |
| 22 |
| EG001 | Inje Cocktail + THC | Participants ingested the Inje Cocktail and a brownie containing 20mg THC | 0 | 22 | 0 | 22 | 0 | 22 |
| EG002 | Inje Cocktail + THC+CBD | Participants ingested the Inje Cocktail and a brownie containing 20mg THC and 640mg CBD | 0 | 22 | 0 | 22 | 8 | 22 |
| Emesis | Gastrointestinal disorders | Non-systematic Assessment |
|
Not provided
Not provided