CBD for Knee Osteoarthritis

Overseen by Michael Alaia, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: NYU Langone Health

Must not be taking: Opioids, CYP3A4 inhibitors

Disqualifiers: Cannabis abuse, Renal failure, Inflammatory arthritis, Major psychiatric illness, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing if CBD tablets that dissolve in the mouth can reduce pain and improve function in people with knee osteoarthritis. The study targets patients who are already doing physiotherapy and home exercises. CBD is thought to work by interacting with the body's system that controls pain and inflammation. CBD is a non-euphoric component of cannabis that has shown potential in relieving pain and reducing inflammation in osteoarthritis.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it mentions that taking certain medications that affect liver enzymes (like CYP3A4 and CYP2C19) might exclude you from participating. It's best to discuss your current medications with the trial doctors to see if they are compatible with the study.

What data supports the effectiveness of the drug for knee osteoarthritis?

Research shows that CBD can reduce pain and improve mobility in animals with osteoarthritis, and it has anti-inflammatory effects in lab studies. This suggests it might help with knee osteoarthritis in humans, although more direct studies are needed. ^{1 2 3 4 5}

Is CBD safe for humans?

CBD, including its pharmaceutical form Epidiolex, has been studied for safety in humans and is generally considered safe. Some studies have reported mild side effects like elevated liver enzymes and vomiting, but it has a very low potential for abuse or physical dependence. ^{4 6 7 8 9}

How does the drug CBD differ from other treatments for knee osteoarthritis?

CBD is unique because it is a component of cannabis that does not cause a high and has shown potential to reduce inflammation and pain in osteoarthritis. Unlike traditional pain medications, CBD can be used as an add-on to existing treatments like paracetamol, potentially enhancing their effects without the typical side effects associated with other pain relievers. ^{3 4 8 10 11}

Research Team

Michael Alaia, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

Adults aged 40-75 with knee osteoarthritis (KL Grade II-III) and pain for at least three months can join. They must have a VAS score of ≥4, indicating moderate to severe pain, and use effective contraception if applicable. Excluded are those with mental impairments, extreme obesity (BMI > 35), liver or kidney issues, certain drug interactions, history of substance abuse or major psychiatric disorders.

Inclusion Criteria

I have moderate knee arthritis.

I am a male and I use effective birth control methods.

I am using two effective birth control methods as a pre-menopausal woman.

Exclusion Criteria

I have severe kidney or liver problems.

I am currently breastfeeding.

I do not have major neurological disorders like dementia or epilepsy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either CBD or placebo orally dissolving tablets three times daily, with assessments on Days 1, 2, 7, 14, 28, 42, and 84

12 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with final assessments at Day 84

4 weeks

Long-term Follow-up

Participants' knee function and satisfaction are assessed using KOOS at Week 60

60 weeks

Treatment Details

Interventions

• Cannabidiol (CBD) (Cannabinoid)
• Placebo (Behavioural Intervention)

Trial Overview The trial is testing whether CBD orally dissolving tablets can reduce pain and improve function in knee osteoarthritis patients compared to a placebo. Participants will not experience any 'high' as the treatment does not contain THC.

Participant Groups

Group I: CBD Group Experimental Treatment 1 Intervention

The first cohort will take two 25mg cannabidiol (total dose: 50mg) Orally Disintegrating Tablets (CBD ODT) three times daily for a maximum dose of 150mg per day.

Group II: Placebo Group Placebo Group 1 Intervention

Cohort 2 will receive the same instructions, but with the placebo Orally Disintegrating Tablets (ODT) instead.

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Dr. Alec C. Kimmelman

NYU Langone Health

Chief Executive Officer

MD and PhD from Mount Sinai School of Medicine

Dr. Nicole M. Adler

NYU Langone Health

Chief Medical Officer since 2023

MD

Orcosa Inc.

Industry Sponsor

Trials

2

Recruited

200+

Orcosa Inc.

Collaborator

Trials

2

Recruited

200+

Findings from Research

Hemp-derived cannabidiol (CBD) has been shown to significantly reduce proinflammatory cytokines and increase anti-inflammatory cytokines in both in vitro and mouse models, indicating its potential as an anti-inflammatory treatment.

In a 4-week study involving dogs with osteoarthritis, both liposomal CBD and nonliposomal CBD effectively decreased pain and improved mobility, with liposomal CBD showing comparable efficacy at a lower dose, and no significant adverse effects were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Verrico, CD., Wesson, S., Konduri, V., et al.[2023]

In a randomized, double-blind, placebo-controlled trial involving 100 patients with acute low back pain, a single dose of 400 mg oral cannabidiol (CBD) did not show superior pain relief compared to a placebo, with similar pain scores reported two hours after administration.

Both groups had comparable lengths of stay in the emergency department and similar usage of rescue analgesia, indicating that CBD did not provide additional benefits in pain management or safety compared to standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain. Bebee, B., Taylor, DM., Bourke, E., et al.[2021]

In a study using male Wistar rats with induced osteoarthritis, local administration of cannabidiol (CBD) significantly reduced pain and increased pain thresholds, indicating its potential as an effective treatment for osteoarthritis pain.

Prophylactic treatment with CBD not only prevented the development of pain but also protected against nerve damage in the joints, suggesting that CBD could be a safe and useful therapeutic option for managing osteoarthritis-related neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Philpott, HT., O'Brien, M., McDougall, JJ.[2022]

In a study of 86 patients with painful knee osteoarthritis, adding high-dose oral cannabidiol (600 mg/day) to ongoing paracetamol treatment did not provide any additional pain relief compared to a placebo, with both groups showing similar reductions in pain scores.

Cannabidiol was associated with a higher frequency of adverse events, including liver enzyme elevations, suggesting potential safety concerns that limit its use as an analgesic supplement in knee osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral cannabidiol (CBD) as add-on to paracetamol for painful chronic osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial. Pramhas, S., Thalhammer, T., Terner, S., et al.[2023]

In a study involving 20 healthy Beagle dogs, repeated oral administration of plant-derived cannabidiol (CBD) was well tolerated, with no significant safety concerns noted over 28 days, although higher doses (12 mg/kg) led to mild gastrointestinal side effects.

The pharmacokinetics of CBD showed a dose-dependent increase in systemic exposure and plasma concentrations, reaching steady state after two weeks, which can inform future dosing strategies for CBD in veterinary medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs. Vaughn, DM., Paulionis, LJ., Kulpa, JE.[2021]

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]

In a study involving 23 dogs with osteoarthritis, cannabidiol (CBD) did not show significant differences in pain relief compared to a placebo based on objective measures like gait analysis and activity counts.

While CBD was generally well-tolerated, some adverse effects were noted, including elevated liver enzymes in 14 dogs and vomiting in 2 dogs, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Effect of Cannabidiol on Naturally Occurring Osteoarthritis-Associated Pain: A Pilot Study in Dogs. Mejia, S., Duerr, FM., Griffenhagen, G., et al.[2022]

In a pilot study involving 20 former elite athletes, topical cannabidiol (CBD) was found to be well-tolerated, with 50% of participants reporting only minor adverse effects such as skin dryness and rash, none of which required medical attention.

Participants experienced significant reductions in self-reported pain levels and pain-related disability over the 6-week study period, indicating that CBD may be an effective option for managing chronic pain in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical cannabidiol is well tolerated in individuals with a history of elite physical performance and chronic lower extremity pain. Hall, N., James, B., Bhuiyan, MAN., et al.[2023]

Cannabidiol (CBD), specifically in its oral formulation Epidiolex, has been shown to have very low abuse potential and is unlikely to cause physical dependence, as demonstrated by studies in rats and nonhuman primates that showed no significant self-administration or withdrawal signs after chronic treatment.

The pharmacokinetic studies confirmed that the doses used in the experiments resulted in therapeutically relevant plasma levels, supporting the safety and efficacy of CBD for treating seizures in severe forms of epilepsy without the risks associated with addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Assessment of the Abuse Potential of Purified Botanical Cannabidiol: Self-Administration, Drug Discrimination, and Physical Dependence. Gray, RA., Heal, DJ., Maguire, DR., et al.[2022]

In a study of 109 patients who underwent total hip or knee replacement surgeries, 22% reported using cannabidiol (CBD) during their treatment period.

Despite the prevalence of CBD use, there was no significant difference in pain satisfaction between those who used CBD and those who did not, indicating a need for further research on the safety and efficacy of CBD in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rates of self-directed perioperative cannabidiol use in patients undergoing total hip or knee arthroplasty. Yu, JS., Premkumar, A., Liu, S., et al.[2021]

A survey of 101 orthopaedic sports medicine providers revealed that 76% believe cannabidiol (CBD) can help with postoperative pain management, and 94% have encountered patients using CBD for pain relief, indicating a perceived therapeutic value.

Despite this belief, 89% of respondents lacked knowledge about CBD's mechanism of action, highlighting a significant knowledge gap that suggests the need for further education and research on CBD's applications in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceptions and Opinions on Cannabidiol in the Orthopaedic Sports Medicine Community. Li, ZI., Chalem, I., Berzolla, E., et al.[2023]

References

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

A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. [2023]

2. Australia pubmed.ncbi.nlm.nih.gov

The CANBACK trial: a randomised, controlled clinical trial of oral cannabidiol for people presenting to the emergency department with acute low back pain. [2021]

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

Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. [2022]

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

Oral cannabidiol (CBD) as add-on to paracetamol for painful chronic osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial. [2023]

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

Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs. [2021]

6. 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]

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

Evaluation of the Effect of Cannabidiol on Naturally Occurring Osteoarthritis-Associated Pain: A Pilot Study in Dogs. [2022]

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

Topical cannabidiol is well tolerated in individuals with a history of elite physical performance and chronic lower extremity pain. [2023]

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

Preclinical Assessment of the Abuse Potential of Purified Botanical Cannabidiol: Self-Administration, Drug Discrimination, and Physical Dependence. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Rates of self-directed perioperative cannabidiol use in patients undergoing total hip or knee arthroplasty. [2021]

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

Perceptions and Opinions on Cannabidiol in the Orthopaedic Sports Medicine Community. [2023]