Clinical trial NCT05049733: The Pharmacokinetics and Pharmacodynamics of a Single Acute Dose of a Hemp-derived Oral Product With a 1:1 Ratio of CBD:CBD-A
Official title: The Pharmacokinetics and Pharmacodynamics of a Single Acute Dose of a Hemp-derived Oral Product With a 1:1 Ratio of CBD:CBD-A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cannabis
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Cultivate Biologics
First posted: 2021-09-20
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: All participants will complete all dose conditions (study arms) in a randomized order
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to examine the pharmacokinetics and pharmacodynamics of a hemp-derived oral product containing cannabidiol (CBD) and cannabidiolic acid (CBD-A) at a 1:1 ratio.

Detailed description: The purpose of the present study is to examine the pharmacokinetics and pharmacodynamics of a novel hemp-derived oral cannabinoid product, at various doses, in healthy adults. The study will utilize a within-subjects, placebo-controlled, double-blind, ascending-dose design. Drug administration will be double blind (the participant and research staff will be unaware of the dose administered). Upon enrollment, participants will complete 4 dosing conditions (placebo, 1 mg/kg, 2 mg/kg, 4 mg/kg of cannabinoids). Each condition will consist of a single acute drug exposure, followed by an 8-hour period to evaluate acute pharmacodynamic and pharmacokinetic (PK) drug effects. Biological specimens (blood and urine) will be obtained throughout these 8 hours to characterize the pharmacokinetics of CBD, CBD-A, delta-9-Tetrahydrocannabinol (THC), and THC-A, as well as other relevant cannabinoids and metabolites. Pharmacodynamic assessments including subjective drug effects, cognitive performance testing, and vital signs will also be collected for 8 hours post-drug administration. For each of the two days after each experimental session, participants will be asked to return to the lab for brief visits (\~20 min) to provide additional biospecimens (\~24 and \~48 hrs after dosing) to allow for further PK analysis. These procedures will be completed 4 separate times by each participant (sessions will be separated by at least 1 week to allow for sufficient drug washout between doses).

Eligibility criteria: Inclusion Criteria:

1. Have provided written informed consent
2. Be between the ages of 18 and 55
3. Be in good general health based on a physical examination, medical history, vital signs, and screening urine and blood tests
4. Test negative for recent cannabis use in urine at the screening visit and again upon admission for each experimental session
5. Test negative for other drugs of abuse, including alcohol, at the screening visit and upon arrival for the experimental session
6. 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 clinic admission
7. Weigh between 110 lbs (50 kg) and 220 lbs (100 kg)
8. Blood pressure at screening visit does not exceed a systolic blood pressure (SBP) of 150 mmHg or a diastolic blood pressure (DBP) of 90 mmHg
9. Self-report prior experience using cannabis or CBD products, but no cannabis, cannabinoid, or hemp product use in the prior 30 days
10. Have not donated blood in the prior 30 days
11. For women of children bearing potential and men with female partners of child-bearing potential, must be willing to use an effective form of contraception during the study and for at least 30 days after the last drug administration session

Exclusion Criteria:

1. Non-medical use of psychoactive drugs other than, nicotine, alcohol, or caffeine in the past 30 days
2. History of or current evidence of significant medical or psychiatric illness judged by the investigator to put the participant at greater risk of experiencing an adverse event due to exposure or completion of other study procedures
3. Use of an over-the-counter (OTC), systemic or topical drug(s), herbal supplement(s), or vitamin(s) within 14 days (or 5 half-lives for that specific drug) of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study results or the safety of the participant
4. Use of a prescription medication (with the exception of birth control prescriptions) within 14 days (or 5 half-lives for that specific drug) of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the participant. This includes any medication metabolized via CYP2D6, CYP2C9, CYP2B10, or which induce/inhibit CYP3A4 enzymes.
5. History of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina)
6. Enrolled in another clinical trial or have received any drug as part of a research study within 30 days prior to dosing
7. Epilepsy or a history of seizures.
8. Individuals with anemia for whom, in the opinion of the study team, participation would pose increased medical risk.

Primary outcomes:
measure: Pharmacokinetics - maximum concentration (CMax) for CBD
timeFrame: 48 hrs
measure: Pharmacokinetics - maximum concentration (CMax) for CBD-A
timeFrame: 48 hrs
measure: Pharmacokinetics - maximum concentration (CMax) for THC
timeFrame: 48 hrs
measure: Pharmacokinetics - maximum concentration (CMax) for THC-A
timeFrame: 48 hrs
measure: Pharmacokinetics - AUC for CBD
timeFrame: 48 hrs
measure: Pharmacokinetics - AUC for CBD-A
timeFrame: 48 hrs
measure: Pharmacokinetics - AUC for THC
timeFrame: 48 hrs
measure: Pharmacokinetics - AUC for THC-A
timeFrame: 48 hrs
measure: Pharmacokinetics - Tmax for CBD
timeFrame: 48 hrs
measure: Pharmacokinetics - Tmax for CBD-A
timeFrame: 48 hrs
measure: Pharmacokinetics - Tmax for THC
timeFrame: 48 hrs
measure: Pharmacokinetics - Tmax for THC-A
timeFrame: 48 hrs
Secondary outcomes:
measure: Driving Under the Influence of Drugs (DRUID) application global impairment score
timeFrame: 8 hrs
measure: Number of Correct Trials on Paced Auditory Serial Addition Task (PASAT)
timeFrame: 8 hrs
measure: Number of Correct Trials on the Digit Symbol Substitution Task (DSST)
timeFrame: 8 hrs
measure: Distance from Central Stimulus on the Divided Attention Task (DAT)
timeFrame: 8 hrs
measure: Feel Drug Effect as assessed by the Drug Effect Questionnaire (DEQ)
timeFrame: 8 hrs
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Behavioral Pharmacology Research Unit
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Tory Spindle, PhD
role: PRINCIPAL_INVESTIGATOR
References: