Cannabidiol Formulations for Healthy Adults

Overseen By Abdul Salama, PharmD

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Saskatchewan

Must not be taking: Cannabis, Psychotropics, Narcotics, others

Disqualifiers: Cardiovascular disease, Schizophrenia, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 week

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires you to stop using certain medications, such as psychotropic medications, narcotic medications, and any drugs that interact with medicinal Cannabis, at least one week before starting. If you're using Cannabis-based therapies or recreational Cannabis, you need a two-month break before joining.

Is cannabidiol (CBD) generally safe for human use?

CBD is generally well tolerated in humans, but it can cause some side effects like diarrhea, sleepiness, and changes in liver function. It may also interact with other medications, so it's important to monitor for any adverse effects. Some CBD products may be contaminated with THC, which can also cause side effects. ^{1 2 3 4 5}

How is the drug Cannabidiol (CBD) unique compared to other treatments?

Cannabidiol (CBD) is unique because it offers potential therapeutic benefits with mild or no psychoactive effects, unlike other cannabis-derived products that contain higher levels of THC (the compound that causes a 'high'). It is also being explored for its safety and effectiveness in various health outcomes, including neurological and immune-related conditions, which are less frequently studied with other treatments. ^{2 6 7 8 9}

What is the purpose of this trial?

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.

Research Team

Abdul Salama, PharmD

Principal Investigator

University of Saskatchewan

Payam Dehghani, MD

Principal Investigator

Pasqua Hospital

Jane Alcorn, DVM;PhD

Principal Investigator

University of Saskatchewan

Eligibility Criteria

This trial is for healthy male adults interested in participating in a study to compare the absorption of two CBD formulations. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and not be taking conflicting medications.

Inclusion Criteria

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

Ability to return for blood draws in the subsequent days

I don't have any significant health issues apart from my current condition.

Exclusion Criteria

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)

I haven't taken any medication that interacts with medicinal Cannabis in the last week.

I haven't taken any antidepressants or similar meds in the last week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single oral doses of CBD formulations to assess relative bioavailability

1 week

1 visit (in-person)

Washout

Participants undergo a washout period to clear the drug from their system before crossover

2 weeks

Crossover Treatment

Participants receive the alternate CBD formulation to compare bioavailability

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cannabidiol

Trial Overview The trial is testing the relative bioavailability (how well a drug gets absorbed into the bloodstream) of two orally administered CBD products: a fast-dissolving cheek strip versus powder form. The goal is to determine which method delivers CBD more effectively.

Participant Groups

Group I: Single Oral Dose Administration of 250mg Buccally or 1000 mg Orally of two CBD formulations Active Control 1 Intervention

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

Group II: Single Oral Dose Administration of 3000mg CBD Extract in Fed vs Fasting Active Control 1 Intervention

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.

Cannabidiol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

University of Saskatchewan

Lead Sponsor

Trials

261

Recruited

156,000+

University of Regina

Collaborator

Trials

59

Recruited

9,100+

Findings from Research

Serious suspected adverse reactions (SARs) to unlicensed cannabidiol (CBD) products were found to be 18.9% of all adverse events, with a higher frequency in men and adults, indicating a need for careful monitoring of its use.

The most common adverse effects associated with unlicensed CBD included mental disorders, hepatic disorders, and worsening of pre-existing epilepsy, particularly in patients also taking antiepileptic medications like clobazam and valproic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. Calapai, F., Esposito, E., Ammendolia, I., et al.[2023]

A systematic review of 4186 studies on cannabidiol (CBD) revealed that most research focuses on neurological outcomes, with significant adverse events reported in this area, highlighting the need for careful assessment of CBD's safety.

There is a notable gap in research regarding the reproductive and developmental toxicity of CBD, suggesting that future studies should prioritize these areas to establish safe intake levels for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. Henderson, RG., Franke, KS., Payne, LE., et al.[2023]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

A systematic review of 12 clinical trials involving 803 participants found that cannabidiol (CBD) is associated with a higher likelihood of withdrawal due to adverse effects compared to placebo, particularly in studies related to childhood epilepsy.

While CBD generally appears well tolerated, significant adverse effects such as abnormal liver function tests and sedation were noted, especially in combination with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Chesney, E., Oliver, D., Green, A., et al.[2021]

In a survey of 239 young adults using cannabis, those who preferred CBD-dominant products were more likely to be female, use cannabis less frequently, and report using it primarily for medical reasons such as pain and psychological issues.

The study found a concerning association between CBD use and increased illicit drug use, suggesting that some individuals may be using CBD as a form of self-medication for underlying psychological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol (CBD) and other drug use among young adults who use cannabis in Los Angeles. Fedorova, EV., Wong, CF., Ataiants, J., et al.[2022]

A survey of 100 cancer patients revealed that most learned about cannabidiol (CBD) from family or friends, but the majority had never tried it, indicating a gap in patient education.

Patients commonly reported interest in using CBD for managing symptoms like pain, anxiety, and nausea, but many had not tried it due to a lack of knowledge and insufficient recommendations from healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol: Knowledge, Beliefs, and Experiences of Patients With Cancer. Butler, TW., Hande, K., Ryan, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Cannabidiol Safety Data: A Systematic Mapping Study. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Are adverse effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination? [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Cannabidiol (CBD) and other drug use among young adults who use cannabis in Los Angeles. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Recreational Cannabidiol: Awareness, Prevalence of use, and Associated Factors in a Representative Sample of the German Population. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Patterns and correlates of cannabidiol product and marijuana co-use in a sample of U.S. young adults. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Cannabidiol: Knowledge, Beliefs, and Experiences of Patients With Cancer. [2021]