The Impact of Product Formulation on the Pharmacokinetics and Pharmacodynamics of Cannabis Edibles

This study will examine the pharmacokinetics and pharmacodynamics of delta-9-tetrahydrocannabinol (THC)-infused chocolates, gummies, and drinks. Healthy adults (N=40) will complete 9 drug administration sessions, including an overnight stay prior to each session. Participants will consume THC containing products in a fasted state; following drug administration, the participants will complete cognitive and psychomotor tasks, subjective assessments, have blood collected, and vital signs monitored.

Study Overview

• Status: Recruiting
• Conditions: Cannabis Use
• Intervention / Treatment: Drug: Placebo; Drug: Cannabis

Detailed Description

The purpose of this study is to examine the pharmacokinetics (PK) and pharmacodynamics (PD) of 3 popular types of cannabis edibles: THC-infused chocolates, gummies, and drinks. This study will utilize a rigorous double-blind, placebo-controlled, within-subjects design. Healthy adults (N=40; 20 males, 20 females) will complete 9 outpatient drug administration sessions in a randomized order. After 8 hours of monitored fasting, participants will consume 1 of 3 types of edibles (chocolates, gummies, or drinks) that are representative of current retail cannabis products. Products will contain 0 (placebo), 10, or 25mg THC. PD assessments include a battery of cognitive/psychomotor performance tasks shown to be sensitive to oral cannabis at these doses and subjective drug effects. Blood samples will be drawn to measure THC and its primary metabolites. Vital signs will be recorded. These procedures will be completed during each of the 9 study sessions.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lindsay Howard; Phone Number: 410-550-0009; Email: lhowar29@jhmi.edu
• Study Contact Backup: Name: Tory Spindle, PhD; Phone Number: 410-550-0529; Email: tspindle@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • Johns Hopkins Behavioral Pharmacology Research Unit
      • Contact: Tory Spindle, PhD; Phone Number: 410-550-0529; Email: tspindle@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Have provided written informed consent.
• Be between the ages of 21 and 55.
• Be in good general health based on screening procedures (e.g., physical exam, medical history interview, vital signs, routine blood tests).
• Test negative for illicit drugs (including cannabis) and test negative for alcohol (0% BAC) at screening and before any study sessions.
• Not be pregnant or nursing (if female). All females must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at admission for each session.
• Have prior experience using THC-dominant cannabis.
• Have a body mass index (BMI) in the range of 16 to 38 kg/m2.
• Have not donated blood in the past 30 days.

Exclusion Criteria

• Self-reported use of illicit drugs (e.g., amphetamine, cannabis, cocaine, methamphetamine, MDMA, LSD, ketamine, heroin, psilocybin, prescription medications not prescribed to the person) in the past 30 days.
• History of significant allergic reaction or significant hypersensitivity to cannabis or to any of the other ingredients in the study products.
• Current concomitant medication use that may interact with the study drug including inhibitors and inducers of CYP2CP and CYP3A4 as well as highly-protein bound drugs and drugs with a narrow therapeutic index such as warfarin, cyclosporine, and amphotericin B.
• History of or current evidence of a significant medical condition that, in the opinion of the investigator or medical staff, will impact the participant's safety or interfere with study outcomes.
• Evidence of current psychiatric condition (based on MINI for DSM-5).
• Been in treatment previously for cannabis use disorder.
• Receiving of any drug as part of a research study within the past 30 days.
• History of epilepsy or other serious medical condition.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Gummy; Participants will self-administer a gummy containing 0mg THC	Drug: Placebo; Placebo will be orally ingested
Experimental: Low Dose Gummy; Participants will self-administer a gummy containing 10mg THC	Drug: Cannabis; Cannabis will be orally ingested; Other Names: marijuana
Experimental: High Dose Gummy; Participants will self-administer a gummy containing 25mg THC	Drug: Cannabis; Cannabis will be orally ingested; Other Names: marijuana
Placebo Comparator: Placebo Chocolate; Participants will self-administer chocolate containing 0mg THC	Drug: Placebo; Placebo will be orally ingested
Experimental: Low Dose Chocolate; Participants will self-administer chocolate containing 10mg THC	Drug: Cannabis; Cannabis will be orally ingested; Other Names: marijuana
Experimental: High Dose Chocolate; Participants will self-administer chocolate containing 25mg THC	Drug: Cannabis; Cannabis will be orally ingested; Other Names: marijuana
Placebo Comparator: Placebo Beverage; Participants will self-administer a beverage containing 0mg THC	Drug: Placebo; Placebo will be orally ingested
Experimental: Low Dose Beverage; Participants will self-administer a beverage containing 10mg THC	Drug: Cannabis; Cannabis will be orally ingested; Other Names: marijuana
Experimental: High Dose Beverage; Participants will self-administer a beverage containing 25mg THC	Drug: Cannabis; Cannabis will be orally ingested; Other Names: marijuana

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Working memory performance as assessed by the 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. Total correct trials out of 90 recorded is primary outcome (lower scores indicate worse performance).	8 hours
Psychomotor performance as assessed by the Correct Trials on the Digit Symbol Substitution Task(DSST)	Computerized version of Digit Symbol Substitution Task will be administered to assess psychomotor performance. Total correct trials in 90 seconds is primary outcome (lower scores indicate worse performance).	8 hours
Attention as assessed by the Mean Distance from the Center Target Stimulus on the Divided Attention Task (DAT)	Computerized version of the Divided Attention Task will be administered to assess attention. Mean distance (in computer pixels) of the mouse cursor from the center target stimulus is primary outcome (lower scores indicate worse performance).	8 hours
Executive functioning as assessed by the Mean Distance from the Center Target Stimulus on the Divided Attention Task (DAT)	Computerized version of the Divided Attention Task will be administered to assess executive functioning. Mean distance (in computer pixels) of the mouse cursor from the center target stimulus is primary outcome (lower scores indicate worse performance).	8 hours
DRiving Under the Influence of Drugs (DRUID) application global impairment score - Acute cognitive impairment	Acute cognitive impairment will be assessed with global impairment score(range 0-100) on the DRUID app (higher scores indicate greater impairment).	8 hours
DRUID application global impairment score - Acute behavioral impairment	Acute behavioral impairment will be assessed with global impairment score(range 0-100) on the DRUID app (higher scores indicate greater impairment).	8 hours
"Like Drug Effect" as assessed by the Drug Effect Questionnaire (DEQ)	The DEQ will be used to obtain subjective ratings of "like drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	8 hours
"Want to take again" as assessed by the Drug Effect Questionnaire	The DEQ will be used to obtain subjective ratings of "want to take drug again". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	8 hours
CMax for THC	Blood concentrations of THC will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The maximum concentrations (Cmax) is determined as the highest concentration reached for each individual.	8 hours
AUC for THC	Blood concentrations of THC will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The area under the curve (AUC) is calculated across all timepoints, minus the baseline.	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CMax for THC metabolite - 11-OH-THC	Blood concentrations of 11-OH-THC will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The maximum concentrations (Cmax) is determined as the highest concentration reached for each individual.	8 hours
CMax for THC metabolite- THCCOOH	Blood concentrations of THCCOOH will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The maximum concentrations (Cmax) is determined as the highest concentration reached for each individual.	8 hours
AUC for THC metabolite - 11-OH-THC	Blood concentrations of 11-OH-THC will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The area under the curve (AUC) is calculated across all timepoints, minus the baseline.	8 hours
AUC for THC metabolite - THCCOOH	Blood concentrations of THCCOOH will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The area under the curve (AUC) is calculated across all timepoints, minus the baseline.	8 hours
Tmax for THC	Blood concentrations of THC will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Time to max concentration (Tmax) will be calculated for each cannabinoid.	8 hours
Tmax for THC metabolite - 11-OH-THC	Blood concentrations of 11-OH-THC will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Time to max concentration (Tmax) will be calculated for each cannabinoid.	8 hours
Tmax for THC metabolite - THCCOOH	Blood concentrations of THCCOOH will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Time to max concentration (Tmax) will be calculated for each cannabinoid.	8 hours
Cmax for CBD	Blood concentrations of CBD will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The maximum concentrations (Cmax) is determined as the highest concentration reached for each individual.	8 hours
Cmax for CBN	Blood concentrations of CBN will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The maximum concentrations (Cmax) is determined as the highest concentration reached for each individual.	8 hours
Cmax for CBG	Blood concentrations of CBG will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The maximum concentrations (Cmax) is determined as the highest concentration reached for each individual.	8 hours
AUC for CBD	Blood concentrations of CBD will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The area under the curve (AUC) is calculated across all timepoints, minus the baseline.	8 hours
AUC for CBN	Blood concentrations of CBN will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The area under the curve (AUC) is calculated across all timepoints, minus the baseline.	8 hours
AUC for CBG	Blood concentrations of CBG will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. The area under the curve (AUC) is calculated across all timepoints, minus the baseline.	8 hours
Tmax for CBD	Blood concentrations of CBD will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Time to max concentration (Tmax) will be calculated for each cannabinoid.	8 hours
Tmax for CBN	Blood concentrations of CBN will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Time to max concentration (Tmax) will be calculated for each cannabinoid.	8 hours
Tmax for CBG	Blood concentrations of CBG will be measured using quantitative liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Time to max concentration (Tmax) will be calculated for each cannabinoid.	8 hours
Psychomotor performance as assessed by attempted Trials on the Digit Symbol Substitution Task(DSST)	Computerized version of Digit Symbol Substitution Task will be administered to assess psychomotor performance. Number of attempted trials is a secondary outcome.	8 hours
Working memory performance as assessed by Reaction Time on Paced Auditory Serial Addition Task (PASAT)	Computerized version of Paced Auditory Serial Addition Task will be administered to assess working memory performance. The secondary outcome is the mean reaction time (in milliseconds) to select correct responses.	8 hours
Attention as assessed by the Number of peripheral integers correct on Divided Attention Task (DAT)	Computerized version of the Divided Attention Task will be administered to assess attention. The secondary outcome is the number of peripheral stimuli correctly identified.	8 hours
Executive functioning as assessed by the Number of peripheral integers correct on Divided Attention Task (DAT)	Computerized version of the Divided Attention Task will be administered to assess executive functioning. The secondary outcome is the number of peripheral stimuli correctly identified.	8 hours
"Unpleasant Drug Effect" as assessed by the Drug Effect Questionnaire	The DEQ will be used to obtain subjective ratings of "unpleasant drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	8 hours
"Feel Drug Effect" as assessed by the Drug Effect Questionnaire-	The DEQ will be used to obtain subjective ratings of "feel drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	8 hours

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Tory Spindle, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 27, 2022
• First Submitted That Met QC Criteria: October 27, 2022
• First Posted (Actual): November 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Marijuana Abuse; nabiximols
• Other Study ID Numbers: IRB00354926; 1R01DA057201-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No