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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the absorption of a new fast-dissolving cannabidiol (CBD) strip placed on the cheek compared to a traditional CBD powder. The goal is to determine which formulation might better manage concussions in NFL athletes. Participants should be healthy adults without significant medical issues, willing to stay at the clinic for 13 hours, and able to return for follow-up blood draws. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative CBD strip.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cannabidiol (CBD) is generally well-tolerated, even in high amounts. One study found CBD to be safe at doses up to 800mg. Therefore, the doses used in the trial, whether taken orally or through cheek strips, should be manageable for most participants.

Studies also indicate that CBD absorbs better when taken with food, meaning the body might take in more CBD if consumed with a meal. However, even without food, CBD has been safe at doses up to 6000mg.

Overall, CBD appears to have a good safety record. Previous studies have not reported significant harmful effects at these levels. This trial is in its early phase, focusing mainly on ensuring safety and understanding how the body absorbs CBD. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these cannabidiol (CBD) treatments because they explore new ways of delivering CBD that might enhance its effectiveness. One approach involves a buccal formulation, where CBD is absorbed through the cheek, potentially allowing for faster and more direct effects by bypassing the digestive system. The other method examines how CBD behaves when taken on an empty stomach versus after a high-fat meal, which could help optimize dosing for different situations. These studies aim to refine CBD administration, potentially leading to more effective and tailored use compared to traditional oral CBD oils or capsules.

What evidence suggests that this trial's cannabidiol formulations could be effective for concussion management in NFL athletes?

This trial will compare different formulations and administration methods of cannabidiol (CBD) in healthy adults. Studies have shown that CBD can help with various issues, such as reducing anxiety and fighting addiction. Research indicates that the method of CBD administration affects its absorption by the body. For instance, taking CBD with a high-fat meal can significantly increase its absorption, allowing more CBD to enter the bloodstream. This trial includes a group receiving a 3000mg CBD extract in fed versus fasting states to evaluate this effect. Additionally, using a fast-dissolving strip inside the cheek may enhance CBD absorption compared to traditional oral methods. The trial will also assess a single oral dose of 250mg buccally versus 1000mg orally to explore this potential benefit. These findings aim to guide the best ways to take CBD for potential benefits. ^{2 5 6 7 8}

Who Is on the Research Team?

Payam Dehghani, MD

Principal Investigator

Pasqua Hospital

Jane Alcorn, DVM;PhD

Principal Investigator

University of Saskatchewan

Abdul Salama, PharmD

Principal Investigator

University of Saskatchewan

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10253521/

Cannabidiol for Oral Health: A New Promising Therapeutical ... Several subjective findings suggest some therapeutic effects of CBD that are strongly supported by research evidence. However, there is a plethora of data ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0753332224001525

Cannabidiol and its application in the treatment of oral ... This paper focuses on the therapeutic potential of CBD in periodontal diseases, pulp diseases, oral mucosal diseases, oral cancer and temporomandibular joint ...

3. mdpi.com mdpi.com/2076-3417/15/10/5736

The Potential of Cannabidiol in the Management of Oral ... CBD treatment across various models has yielded consistent therapeutic outcomes, as follows: (i) Infection reduction and antibacterial and antifungal effects ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06574100

Relative Bioavailability of Two Orally Administered CBD ... The results of this study will help guide dosage formulation choices as well as dosing regimens in NFL athletes for concussion management.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9841308/

The safety and efficacy of low oral doses of cannabidiol At doses of 300–400 mg, there is evidence of efficacy with respect to reduced anxiety, as well as anti‐addiction effects in drug‐dependent individuals.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4449284/

Safety and pharmacokinetics of oral cannabidiol when ... The main findings of this study were that CBD was well tolerated at doses up to 800mg (approximately 10–15 mg/kg), with no significant pharmacokinetics changes ...

7. tga.gov.au tga.gov.au/sites/default/files/review-safety-low-dose-cannabidiol.pdf

Safety of low dose cannabidiol The review found that cannabidiol presents a good safety and tolerability profile at the low dose range of under 60mg/day. • The review identified that ...

8. fda.gov fda.gov/media/152317/download

Safety of CBD in Humans – A Literature Review (As of ... Clinical trials of repeated doses in patients have provided, compared to other settings, the most comprehensive safety data on repeated oral CBD use. But ...