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

Trial Summary

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 CBD safe for human use?

CBD, including products like Epidiolex, is generally considered safe for human use, but it can cause side effects such as sleep disturbances, sedation, and liver enzyme changes. It may also interact with other medications, so it's important to discuss its use with a healthcare provider, especially if you are taking other drugs. ^{1 2 3 4 5}

How is the drug CBD unique for treating osteoarthritis?

CBD (Cannabidiol) is unique for treating osteoarthritis because it is derived from cannabis and is known for its anti-inflammatory properties, which may help reduce joint pain and inflammation. Unlike some traditional treatments, CBD is often used in a more natural form and may offer an alternative for those seeking non-opioid pain relief options. ^{6 7 8 9 10}

What is the purpose of this trial?

Osteoarthritis is a disease that affects millions of Americans and is the leading cause of persistent pain and physical disability in the older adult population. Many physically active Americans have reported pain-relieving effects of cannabidiol (CBD) that can reduce or eliminate use of nonsteroidal anti-inflammatory drugs (NSAIDs) for activity-related pain with minimal to no side effects. Long-term use of over-the-counter medications, including NSAIDs, can pose a significant health risk, and therefore clinical research on the safety and efficacy of CBD is needed.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects. [2020]

3. Italy pubmed.ncbi.nlm.nih.gov

Pharmacology and legal status of cannabidiol. [2021]

4. United States 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. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Cartilage protective and anti-analgesic effects of ALM16 on monosodium iodoacetate induced osteoarthritis in rats. [2020]

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

Effectiveness of topical ozonated oil in severe osteoarthritis: A randomised, triple-blinded, placebo-controlled study. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Isovitexin Depresses Osteoarthritis Progression via the Nrf2/NF-κB Pathway: An in vitro Study. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

[Effectiveness and tolerance of standardized willow bark extract in arthrosis patients. Randomized, placebo controlled double-blind study]. [2019]

10. Ireland pubmed.ncbi.nlm.nih.gov

Extracts of Oldenlandia diffusa protects chondrocytes via inhibiting apoptosis and associated inflammatory response in osteoarthritis. [2023]