Relative Bioavailability of Two Orally Administered CBD Formulations in Healthy Male Adults

Phase 1

Recruiting

• Conditions: Pharmacokinetics
• Interventions: Drug: Cannabidiol

• Registration Number: NCT06574100
• Lead Sponsor: University of Saskatchewan

Brief Summary

This project is aimed at understanding whether a new fast-dissolving cheek-administered cannabidiol strip will be absorbed better into the body than cannabidiol powder. The results of this study will help guide dosage formulation choices as well as dosing regimens in NFL athletes for concussion management.

Detailed Description

Cannabis formulations are typically administered by the oral route of administration. This route represents the most common administration route for most pharmaceuticals due to the ease of administration and convenience. Inhalational products are not acceptable for the sport's athlete population due to potential damage to lung tissues. Topical products do not have adequate bioavailability to meet our therapeutic objectives. Our PK studies, then, need to employ the same dosage form and route of administration we expect to use in future clinical efficacy trials.

Given the low bioavailability expected with CBD oral formulations, we wish to assess two different formulations and the relative extent of CBD absorption. Our future planned CBD intervention studies in athletes will require use of larger doses of CBD. The formulation with the larger bioavailability will help to reduce the overall size of the dose utilized and therefore reduce the amount of product exposure in our clinical intervention studies. This will increase the likelihood that a Cannabis company can supply the necessary amount of product and reduce the overall cost associated with the studies. Generally speaking, based on current literature published around CBD administration for therapeutic application, higher doses of CBD (i.e., 50mg/kg/d) were found to correlate to more positive outcomes than lower doses (i.e., 1mg/kg/d). Assuming an average weight of 70 kg, a 1000 mg dose would be around 14.29 mg/kg, and a 3000 mg dose around 42.86 mg/kg. This will allow us to investigate the pharmacokinetics of CBD on both ends of the hypothetical efficacy trend. Studies have examined single orally administered doses up to 6000 mg with no serious adverse effects reported.

Study Timeline

• Study First Submitted: 2024-06-28
• Study First Submitted QC: 2024-08-23
• Study First Posted: 2024-08-27
• Study Start: 2024-10-26
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30
• Primary Completion: 2025-11
• Study Completion: 2025-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

1. Age 18 - 35 years old
2. Clinical labs within the stated normal range of the Royal University Hospital Test Centre, or values outside the stated normal range that are not of clinical significance as determined by the qualified investigator.
3. No clinically significant disease on medical history or clinically significant findings on physical examination including vital signs as determined by the qualified investigator.
4. Ability to stay in the clinic trial unit for 13 hours on the day of each single oral dose.
5. Ability to return for blood draws in the subsequent days.

Exclusion Criteria

1. History or presence of significant gastrointestinal, liver or kidney disease or any other condition known to interfere with drug pharmacokinetics including bioavailability or increase risk of adverse effects.
2. History or presence of serious cardiovascular disease, such as ischaemic heart disease, arrhythmias, poorly controlled hypertension or severe heart failure
3. Males whose partners are trying to conceive (i.e. male subjects intending to start a family during the study period)
4. Lack of medically acceptable contraception by participants whose female partners have childbearing potential for the duration of the study.
5. Personal or family history of schizophrenia or any other psychotic disorder
6. Current or past drug or alcohol dependence or abuse
7. Use of Cannabis-based therapy within 2 months (Participants who have previously used a Cannabis-based therapy may be included if they have a 2-month period without use of Cannabis-based therapy prior to enrolment in the study)
8. Use of recreational Cannabis within 2 months (Participants who have previously used recreational Cannabis may be included if they have a 2-month period without use of recreational Cannabis prior to enrolment in the study)
9. Use of psychotropic medications with serotonergic activity (e.g. Selective Serotonin Reuptake Inhibitors, Tricyclic Antidepressants, Atypical Neuroleptics) within one week
10. Use of narcotic medications (e.g. Codeine, Morphine, Oxycontin) within one week
11. Use of any other medication known to interact with medicinal Cannabis within one week.
12. Allergy or known intolerance to any of the compounds within the study preparation.
13. Resting heart rate HR < 50 bpm or > 100 bpm or seated blood pressure < 100/60 or higher than 140/90
14. Inability of study participants to attend and complete all study visits
15. Bleeding disorder
16. Known low hematocrit

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Single Oral Dose Administration of 250mg Buccally or 1000 mg Orally of two CBD formulations	Cannabidiol	participants receiving the buccal formulation will be required to receive 10 strips by the cheeks, they will be instructed to only swallow at maximum once every 2 mins for the first 5 mins. This is to minimize the amount of CBD that will be carried into the GIT. This buccal administration group will receive 2 strips at a time, one on each cheek side, following 5 mins of dissolving, patients will receive 100mL of water to swish the residue in their mouths and swallow, then receive another pair of strips to repeat the process for a total of 5 times over the course of 30 minutes (i.e., 10 strips total). The group receiving the 1000mg oral CBD extract will mimic the buccal group in that they will receive that dose over the course of 30 minutes in 5 parts, 200mg per part, and will drink 100mL of water to accompany its administration
Single Oral Dose Administration of 3000mg CBD Extract in Fed vs Fasting	Cannabidiol	In the fasting group, participants will be asked to fast overnight (at least 10 hours fast) but are allowed to drink water.In the fed state group, participants will start their meal 30 minutes prior to receiving the dose. The meal will consist of high caloric (800-1000 Cal), high fat (\~50% of total calories), with protein, and carbohydrates (\~150 kcal, and \~250 kcal, respectively) content. No food will be administered 4 hours after the dose, and no water will be given 1 hour prior to dose administration and 1 hour after administration. The dose will be given however with a total of 235 mL of water.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Parameters	1 week of samples will be collected. 2 week washout. Then another week of samples after cross over	half-life

Secondary Outcome Measures

Name	Time	Method
Optimal washout periods	3 weeks	Measure CBD and it's metabolites over the course of the study to determine what the optimal washout period is for future studies
Tolerability of the drug using the Integrated Addendum to ICH E6(R1)	During the first week of administration and the 4th week of administration	Tolerability of the study drug will be determined by reporting of incidence of adverse events for each participant.
Safety of the drug using the Integrated Addendum to ICH E6(R1)	During the first week of administration and the 4th week of administration	Safety will be assessed by reporting of incidence of adverse events for each participant.
Compare Fed vs Fast state on oral absorption kinetics	1 week of samples will be collected. 2 week washout. Then another week of samples after cross over	relative bioavailability (F)

Trial Locations

Locations (1)

University of Saskatchewan; 🇨🇦 Saskatoon, Saskatchewan, Canada