Interactions Between Cannabinoids and Cytochrome P450-Metabolized Drugs

NCT04201197 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: IRB00207237U54AT008909
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Drug-Interactions

Outcome Measures

Primary Outcomes (6)

• 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.

  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

Secondary Outcomes (4)

• Caffeine AUC in Plasma

  24 hours

• Omeprazole AUC in Plasma

  24 hours

• Dextromethorphan AUC in Plasma

  24 hours

• Midazolam AUC in Plasma

  24 hours

Study Arms (3)

Inje Cocktail

ACTIVE COMPARATOR

Single oral administration of caffeine (100mg), omeprazole (20mg), losartan (25mg), dextromethorphan (30mg), and midazolam (1mg)

Drug: Inje cocktail

Inje Cocktail + THC extract

EXPERIMENTAL

Single oral administration of Inje Cocktail + brownie infused with cannabis extract containing 20mg THC

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

Drug: Inje cocktail; Drug: THC/CBD Cannabis Extract

Interventions

Inje cocktail DRUG

Acute drug exposure

Inje Cocktail; Inje Cocktail + THC extract; Inje Cocktail + THC/CBD extract

THC Cannabis extract DRUG

Acute drug exposure

Inje Cocktail + THC extract

THC/CBD Cannabis Extract DRUG

Acute drug exposure

Inje Cocktail + THC/CBD extract

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Washington State University: collaborator
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

• 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.

  PMID: 36780161 DERIVED

Results Point of Contact

• Title: Dr. Ryan Vandrey
• Organization: Johns Hopkins School of Medicine

rvandrey@jhmi.edu

410-550-4036

Study Officials

• Ryan Vandrey, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Placebo controlled, double blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2019
• First Posted: December 17, 2019
• Study Start: November 10, 2020
• Primary Completion: March 16, 2022
• Study Completion: July 28, 2022
• Last Updated: July 24, 2023
• Results First Posted: July 24, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After publication of the primary outcomes. Availability is indefinite.
• Access Criteria: Send request to PI.

Locations

US (1)