Trial Outcomes & Findings for Interactions Between Cannabinoids and Cytochrome P450-Metabolized Drugs (NCT NCT04201197)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

22 participants

Primary outcome timeframe

24 hours

Results posted on

2023-07-24

Participant Flow

This was a within-subjects design, so all participants were exposed to all three conditions in a randomized order.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	22
Overall Study Placebo, THC, THC+CBD	3
Overall Study Placebo, THC+CBD, THC	3
Overall Study THC, Placebo, THC+CBD	3
Overall Study THC, THC+CBD, Placebo	3
Overall Study THC+CBD, THC, Placebo	3
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Interactions Between Cannabinoids and Cytochrome P450-Metabolized Drugs

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Evaluable Study Completers n=18 Participants All study completers completed the following three conditions, in a randomized order: 1. Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) 2. Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC 3. Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Age, Continuous	30 years STANDARD_DEVIATION 7 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order.

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

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Losartan Area Under the Curve (AUC) in Plasma	164 h*ng/mL Geometric Coefficient of Variation 74	185 h*ng/mL Geometric Coefficient of Variation 72	289 h*ng/mL Geometric Coefficient of Variation 66

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Peak Change From Baseline Number of Correct Trials on Paced Auditory Serial Addition Task (PASAT)	-1.1 Correct trials Standard Deviation 14.2	-6.6 Correct trials Standard Deviation 19.1	-22.7 Correct trials Standard Deviation 24.6

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Peak Change From Baseline Cognitive Performance as Assessed by the Divided Attention Task	-2.1 Computer pixels Standard Deviation 9.4	15.9 Computer pixels Standard Deviation 24.7	32.7 Computer pixels Standard Deviation 39.2

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Drug Effect Questionnaire (DEQ) - Peak Score for Feel Drug Effect	9.4 Score on a scale Standard Deviation 27.8	59.2 Score on a scale Standard Deviation 31.1	72.8 Score on a scale Standard Deviation 25.9

PRIMARY outcome

Timeframe: 8 hours

Population: All participants were exposed to each of the 3 conditions

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.

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Number of Correct Trials on the Digit Symbol Substitution Task (DSST)	2.5 Correct trials Standard Deviation 7.5	-2.7 Correct trials Standard Deviation 11.2	-9.9 Correct trials Standard Deviation 17.6

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Peak Change From Baseline Beats Per Minute for Heart Rate (HR)	-4.4 Beats per minute Standard Deviation 12.4	10.1 Beats per minute Standard Deviation 14.1	25.4 Beats per minute Standard Deviation 20.9

SECONDARY outcome

Timeframe: 24 hours

Population: This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order.

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

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Caffeine AUC in Plasma	18948 h*ng/mL Geometric Coefficient of Variation 58	18554 h*ng/mL Geometric Coefficient of Variation 61	26264 h*ng/mL Geometric Coefficient of Variation 56

SECONDARY outcome

Timeframe: 24 hours

Population: This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order.

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

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Omeprazole AUC in Plasma	385 h*ng/mL Geometric Coefficient of Variation 90	379 h*ng/mL Geometric Coefficient of Variation 86	1183 h*ng/mL Geometric Coefficient of Variation 86

SECONDARY outcome

Timeframe: 24 hours

Population: This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order.

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

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Dextromethorphan AUC in Plasma	10.4 h*ng/mL Geometric Coefficient of Variation 108	13.2 h*ng/mL Geometric Coefficient of Variation 112	13.6 h*ng/mL Geometric Coefficient of Variation 104

SECONDARY outcome

Timeframe: 24 hours

Population: This was a within-subjects design in which all participants were exposed to all three conditions in a randomized order.

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

Outcome measures

Outcome measures
Measure	Inje Cocktail + Placebo n=18 Participants Single oral administration of Inje Cocktail: caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg) \+ placebo brownie	Inje Cocktail + THC n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC	Inje Cocktail + THC/CBD n=18 Participants Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC and 640mg CBD
Midazolam AUC in Plasma	23 h*ng/mL Geometric Coefficient of Variation 101	24 h*ng/mL Geometric Coefficient of Variation 75	36 h*ng/mL Geometric Coefficient of Variation 84

Adverse Events

Inje Cocktail + Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Inje Cocktail + THC

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Inje Cocktail + THC+CBD

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Inje Cocktail + Placebo n=22 participants at risk Participants ingested the Inje Cocktail and a brownie containing no cannabis	Inje Cocktail + THC n=22 participants at risk Participants ingested the Inje Cocktail and a brownie containing 20mg THC	Inje Cocktail + THC+CBD n=22 participants at risk Participants ingested the Inje Cocktail and a brownie containing 20mg THC and 640mg CBD
Gastrointestinal disorders Nausea	0.00% 0/22 • up to 38 days	0.00% 0/22 • up to 38 days	27.3% 6/22 • Number of events 6 • up to 38 days
Gastrointestinal disorders Emesis	0.00% 0/22 • up to 38 days	0.00% 0/22 • up to 38 days	9.1% 2/22 • Number of events 2 • up to 38 days

Additional Information

Dr. Ryan Vandrey

Johns Hopkins School of Medicine

Phone: 410-550-4036

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place