CBD for Osteoarthritis

(SLACK-OA Trial)

Overseen By Paul A. Borsa, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Florida

Must not be taking: Cannabis, Enzyme-modifying drugs

Disqualifiers: Pregnancy, Major surgery, BMI ≥ 45, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether CBD (Cannabidiol Extract) can relieve pain for individuals with knee osteoarthritis, a joint condition causing pain and stiffness. Researchers aim to determine if CBD can serve as a safe, effective alternative to NSAIDs (common pain relievers) without their side effects. Participants will receive either a CBD-rich hemp supplement or a placebo (a harmless substance resembling the real treatment) to compare outcomes. The trial seeks individuals diagnosed with knee osteoarthritis who experience moderate to severe pain during physical activity. As a Phase 1, Phase 2 trial, this research focuses on understanding how CBD works in people and measuring its effectiveness in an initial group, offering participants a chance to contribute to groundbreaking pain relief research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using cannabis or certain enzyme-modifying drugs. It's best to discuss your specific medications with the trial team.

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

Research has shown that cannabidiol (CBD) is generally safe. The World Health Organization states that CBD is well-tolerated and has few side effects. Common mild side effects include fatigue, diarrhea, and changes in appetite or weight. These are minor compared to other drugs used for similar purposes.

Studies have not linked CBD to major serious side effects, indicating they are rare. CBD has been researched for various conditions, such as pain relief in arthritis, and has shown promise in reducing pain.

Overall, CBD is considered safe to use, but individual reactions can vary. Consulting a healthcare provider before starting any new treatment is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for osteoarthritis?

Researchers are excited about using cannabidiol (CBD) extract for osteoarthritis because it offers a natural alternative to traditional pain relievers like NSAIDs and corticosteroids. Unlike these standard treatments, which mainly focus on reducing inflammation or suppressing the immune response, CBD interacts with the body's endocannabinoid system, potentially modulating pain and inflammation in a novel way. This full-spectrum CBD formulation includes a variety of cannabinoids, terpenes, and essential oils, which together might provide a more comprehensive therapeutic effect without the psychoactive impact of THC.

What evidence suggests that this treatment might be an effective treatment for osteoarthritis?

Research has shown that cannabidiol (CBD) may help reduce inflammation and pain from arthritis. In studies, applying CBD directly to the skin blocked pain from osteoarthritis. Some research even suggests that early use of CBD might prevent pain from developing. People using CBD have reported needing fewer other painkillers, such as NSAIDs, which can have long-term side effects. In this trial, participants will receive either a full-spectrum CBD-rich formulation or a placebo. These findings suggest that CBD could be a good option for managing osteoarthritis pain. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with knee osteoarthritis experiencing moderate to severe pain (at least 4 out of 10) during physical activity. It's aimed at those who seek an alternative to NSAIDs for managing their pain.

Inclusion Criteria

I have been diagnosed with knee osteoarthritis.

I experience knee pain of 4 or more out of 10 when active.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Testing

Participants undergo baseline testing before the dosing regimen begins

1 week

1 visit (in-person)

Treatment

Participants receive a 30-day dosing regimen of either CBD or placebo

4 weeks

Weekly visits (virtual)

Wash-out

A 2-week wash-out period before the cross-over phase

2 weeks

Cross-over Treatment

Participants switch to the alternate treatment (CBD or placebo) for another 30-day dosing regimen

4 weeks

Weekly visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol (CBD) Extract

Trial Overview

The study tests the safety and effectiveness of Cannabidiol (CBD) extract in reducing knee pain caused by osteoarthritis, compared to a placebo. Participants will not know if they are receiving CBD or the placebo.

How Is the Trial Designed?

Group I: Active Drug Active Control 1 Intervention

Hemp supplement is a full spectrum CBD-rich formulation (\~10%) containing very low levels of THC (\<0.3%), along with all naturally occurring minor cannabinoids, terpenes, and essential oils from the plant extract.

Group II: Vehicle Control Placebo Group 1 Intervention

A medium chain triglyceride-based mixing agent blended with coconut oil will be used as the placebo.

Cannabidiol (CBD) Extract 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 Epidyolex for:

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

Approved in Canada as Sativex for:

• Symptomatic relief of spasticity in adult patients with multiple sclerosis
• Adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis
• Adjunctive analgesic treatment for moderate to severe pain in adult patients with advanced cancer

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

Isovitexin (IVX) has been shown to effectively suppress inflammation and extracellular matrix degeneration in chondrocytes, which are crucial for joint health, indicating its potential as a therapeutic agent for osteoarthritis (OA).

The mechanism of action for IVX involves the inhibition of the NF-κB signaling pathway through its interaction with the Nrf2 protein, suggesting that targeting this pathway could be a promising strategy for OA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isovitexin Depresses Osteoarthritis Progression via the Nrf2/NF-κB Pathway: An in vitro Study. Hu, X., Li, R., Sun, M., et al.[2022]

Epidiolex, the only FDA-approved CBD-based drug, has been studied for its medicinal benefits and potential side effects across various clinical trials, focusing on both physiological and neurological conditions.

The review highlights that the outcomes of these trials can vary significantly based on the funding source, which may influence the reported efficacy and safety of Epidiolex and other CBD formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. Pauli, CS., Conroy, M., Vanden Heuvel, BD., et al.[2020]

A single oral dose of 750 mg of cannabidiol (CBD) showed significantly increased exposure when taken with a high-fat/calorie meal, with a 3.8-fold increase in overall exposure (AUC0-∞) and a 5.2-fold increase in maximum concentration (Cmax) compared to fasting.

CBD was well-tolerated with no severe adverse events reported, indicating its safety in healthy adults, while its absorption was also enhanced by low-fat meals, whole milk, and alcohol, albeit to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Crockett, J., Critchley, D., Tayo, B., et al.[2021]

ALM16, a herbal mixture of Astragalus membranaceus and Lithospermum erythrorhizon, showed significant chondroprotective effects against osteoarthritis in both in vitro and in vivo models, reducing cartilage degradation and inflammation.

In animal studies, ALM16 effectively decreased pain and inflammation associated with osteoarthritis, demonstrating improvements in cartilage health comparable to or better than a standard drug control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cartilage protective and anti-analgesic effects of ALM16 on monosodium iodoacetate induced osteoarthritis in rats. Choi, DJ., Choi, SI., Choi, BR., et al.[2020]

Cannabidiol (CBD) is a non-psychoactive compound from cannabis that can counteract the psychotropic effects of THC and has gained popularity in various therapeutic products, especially after the FDA approved Epidiolex® for treating severe epilepsy in children.

Despite its therapeutic potential, there is a lack of consistent international regulations governing the marketing and authorization of CBD products, which raises concerns about product safety and efficacy for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. Brunetti, P., Lo Faro, AF., Pirani, F., 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 2-week randomized controlled trial with 78 participants, willow bark extract significantly reduced pain in osteoarthritis patients compared to placebo, with a 14% decrease in WOMAC pain scores.

Both patient and investigator assessments confirmed the effectiveness of willow bark extract, indicating it has a moderate analgesic effect for managing osteoarthritis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and tolerance of standardized willow bark extract in arthrosis patients. Randomized, placebo controlled double-blind study]. Schmid, B., Lüdtke, R., Selbmann, HK., et al.[2019]

A randomized controlled trial involving 80 patients over 60 days showed that topical ozonated oil significantly relieved pain in osteoarthritis patients, particularly those with severe cases, compared to a placebo.

This study is the first to demonstrate the effectiveness of topical ozonated oil in alleviating pain for patients with severe osteoarthritis, highlighting its potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of topical ozonated oil in severe osteoarthritis: A randomised, triple-blinded, placebo-controlled study. Anzolin, AP., Collares, DDS., Tadeu Dos Santos, R., et al.[2021]

Oldenlandia diffusa (OD) shows promise in treating osteoarthritis by reducing inflammation and preventing cartilage degradation, as demonstrated in both in vitro and in vivo studies involving mouse models.

The active component β-sitosterol in OD inhibits chondrocyte apoptosis and the MAPK pathway, which are key mechanisms in alleviating the symptoms of osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extracts of Oldenlandia diffusa protects chondrocytes via inhibiting apoptosis and associated inflammatory response in osteoarthritis. Lou, C., Lin, C., Wang, W., et al.[2023]

In a study involving 45 children with treatment-resistant epilepsy, cannabidiol (CBD) significantly reduced major seizure frequency by 54-72% and increased seizure-free days by an average of 7.52 days over 36 months, demonstrating its efficacy as an adjunctive treatment.

CBD was well tolerated at doses up to 50 mg/kg/day, although children who increased their dose beyond 25 mg/kg/day initially reported more adverse events; however, the overall rate of adverse events decreased after transitioning to higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program. Park, YD., Linder, DF., Pope, J., et al.[2021]

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