CBD + THC for Knee Osteoarthritis

Overseen By Jaye Minghine

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Richard Harris

Must not be taking: Opioids, Valproate, Clobazam, Warfarin

Disqualifiers: Severe cardiovascular disease, Epilepsy, Liver failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 16 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial is being done to better understand how daily treatment with Tetrahydrocannabinol (THC), Cannabidiol (CBD), or the combination of CBD plus THC affects knee osteoarthritis pain and other related symptoms. Consented participants will have a screening period and visit (up to 30 days to treatment start). If participants pass the screening phase, they will be randomly assigned to take one of the investigational study drugs. For this study, participants will not know when or if they are taking CBD, THC, THC plus CBD, and when or if taking placebo. Clinical pain will be assessed at multiple times throughout the study, and eligibility will be re-assessed at two weeks into the treatment period. It is possible that subjects will not be able to participate in the study after 14 days of of treatment. The treatment period will take approximately 16 weeks and then a follow-up period for approximately 2 weeks. In addition to treatment, participants will have clinical assessments, blood draws, questionnaires, daily pain diaries, sensory testing, as well as have functional connectivity magnetic resonance imaging (fcMRI).

Will I have to stop taking my current medications?

The trial requires that you maintain a stable treatment regimen for chronic knee osteoarthritis pain, meaning you should not start new treatments like physical therapy. You must also avoid certain medications, such as opioids (except tramadol) and specific drugs affecting liver enzymes. Additionally, you need to refrain from pain medications like NSAIDs and acetaminophen for 12 hours before certain tests.

What data supports the effectiveness of the drug CBD + THC for knee osteoarthritis?

Research shows that CBD, a component of the drug, has anti-inflammatory and pain-relieving properties, which have been effective in reducing pain and improving mobility in animal models of osteoarthritis. Additionally, CBD has shown promise in reducing pain and inflammation in preclinical models of arthritis, suggesting potential benefits for knee osteoarthritis. ^{1 2 3 4 5}

Is CBD and THC safe for humans?

Research shows that CBD (Cannabidiol) and THC (Tetrahydrocannabinol) have been used safely in various studies, including for conditions like epilepsy and osteoarthritis. However, more research is needed to fully understand their safety, especially when used together or in different conditions. ^{1 3 6 7 8}

How is the drug CBD + THC unique for treating knee osteoarthritis?

The combination of CBD (Cannabidiol) and THC (Tetrahydrocannabinol) for knee osteoarthritis is unique because it uses cannabinoids, which are compounds found in cannabis plants, to potentially reduce pain and inflammation. This approach is different from traditional treatments like pain relievers or anti-inflammatory drugs, as it targets the body's endocannabinoid system, which plays a role in regulating pain and inflammation. ^{9 10 11 12 13}

Research Team

Steve Harte, PhD

Principal Investigator

University of Michigan

Eligibility Criteria

This trial is for English-speaking, right-handed adults with knee osteoarthritis who haven't used cannabis or CBD in the past month. They must be able to lie still for MRI scans and refrain from certain activities and medications before testing. Pregnant women, those planning knee surgery, or individuals with severe physical impairments or specific medical conditions are excluded.

Inclusion Criteria

No contraindications to magnetic resonance imaging (MRI) (for example (e.g.), metal implants)

I agree to use birth control during and after the study.

I have had knee pain that is moderate to severe for 6 months or more.

Exclusion Criteria

I am currently taking valproate, clobazam, or warfarin.

Serum total bilirubin ≥ 2.5 milligrams per deciliter (mg/dL); or,

I have used cannabis or CBD in the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

1 visit (in-person)

Treatment

Participants receive daily treatment with either THC, CBD, or a combination of both for knee osteoarthritis pain

16 weeks

Multiple visits for clinical assessments, blood draws, and fcMRI

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Cannabidiol (CBD)
• Placebo
• Tetrahydrocannabinol (Marinol® or generic equivalent (e.g., dronabinol))

Trial Overview The study tests how daily treatment with THC (Tetrahydrocannabinol), CBD (Cannabidiol), their combination, or a placebo affects pain from knee osteoarthritis over approximately 18 weeks. Participants will undergo clinical assessments, blood draws, questionnaires, pain diaries, sensory testing, and brain imaging without knowing which treatment they receive.

Participant Groups

Group I: Tetrahydrocannabinol (THC) Experimental Treatment 1 Intervention

Up to 10 mg/day.

Group II: Cannabidiol (CBD) Experimental Treatment 1 Intervention

Up to 150 mg/day.

Group III: CBD plus THC Experimental Treatment 2 Interventions

Up to 150 mg/day CBD plus up to 10 mg/day THC.

Group IV: Placebo Placebo Group 1 Intervention

Cannabidiol (CBD) is already approved in United States, European Union 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

Who Is Running the Clinical Trial?

Richard Harris

Lead Sponsor

Trials

1

Recruited

200+

Steven E Harte, PhD

Lead Sponsor

Trials

1

Recruited

200+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

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]

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 study of 195 patients undergoing total hip and knee arthroplasty, 16.4% reported using CBD/THC products during the perioperative period, with higher usage in knee arthroplasty patients (22.6%) compared to hip arthroplasty patients (11.7%).

Despite the use of CBD/THC products, there was no significant difference in opioid consumption, pain scores, or length of hospital stay between users and non-users, suggesting that these products may not significantly impact post-operative opioid requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Tetrahydrocannabinol and Cannabidiol Products in the Perioperative Period Around Primary Unilateral Total Hip and Knee Arthroplasty. Runner, RP., Luu, AN., Nassif, NA., et al.[2021]

In this study, cannabidiol (CBD) demonstrated significant pain relief and anti-inflammatory effects in various animal models of osteoarthritis, with effectiveness increasing at higher doses (5, 10, 20, and 40 mg/kg).

Combining CBD with standardized bioflavonoid compositions enhanced its efficacy, suggesting that a multi-component approach may be necessary for optimal treatment of osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antinociceptive and Anti-Inflammatory Properties of Cannabidiol Alone and in Combination with Standardized Bioflavonoid Composition. Yimam, M., O'Neal, A., Horm, T., et al.[2021]

Cannabidiol (CBD) shows potential as a treatment for osteoarthritis (OA) by targeting over 60 molecular pathways, with both beneficial and harmful effects identified through computational and experimental methods.

The study highlights the importance of PPARγ in CBD's therapeutic effects while also revealing that CBD can cause heat hyperalgesia through the upregulation of certain receptor channels, indicating a complex interaction in its mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computational Approach Reveals Pronociceptive Potential of Cannabidiol in Osteoarthritis: Role of Transient Receptor Potential Channels. Mlost, J., Kędziora, M., Starowicz, K.[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 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]

In a study of 15 patients with treatment-resistant epilepsy, 12 weeks of treatment with pharmaceutical-grade cannabidiol (CBD) showed minor improvements in white matter integrity, specifically increasing fractional anisotropy in certain brain tracts.

The results suggest that while CBD may have some short-term effects on white matter structure, these changes are relatively minor and indicate that CBD's impact on brain integrity may not be significant in the context of treatment for epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

White matter integrity after cannabidiol administration for treatment resistant epilepsy. Houston, JT., Nenert, R., Allendorfer, JB., et al.[2022]

In a study of 108 patients with juvenile osteochondritis dissecans (JOCD), 29% were found to have bilateral lesions, highlighting the importance of evaluating both knees in affected individuals.

Younger age at presentation and being female were identified as significant risk factors for developing bilateral JOCD, while lesion location and stability did not show a statistical difference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Bilateral JOCD of the Knee and Associated Risk Factors. Cooper, T., Boyles, A., Samora, WP., et al.[2022]

A case study of a patient with osteochondritis dissecans (OD) revealed that initial arthroscopic surgery to remove loose bodies was insufficient, as the patient later developed a new unstable chondral flap, indicating the need for thorough follow-up and assessment after initial treatment.

Revision surgery using bioresorbable pins and screws to fix the chondral flap resulted in satisfactory outcomes, highlighting the importance of open surgical intervention for accurate evaluation and effective treatment of complex OD cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revision of Failed Osteochondritis dissecans Surgical Treatment: Case Report. Maiotti, M., Rossi, V., Armocida, D.[2023]

In a study of 87 patients who underwent internal fixation for unstable osteochondritis dissecans (OCD) lesions, 76% had healed lesions after at least 2 years, showing that both skeletally immature and mature patients heal at similar rates.

Lateral condylar location of the OCD lesion was identified as a significant independent risk factor for treatment failure, indicating that the location of the lesion may influence surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Internal Fixation of Unstable Osteochondritis Dissecans: Do Open Growth Plates Improve Healing Rate? Wu, IT., Custers, RJH., Desai, VS., et al.[2019]

In a study of 31 patients with complex osteochondral defects in the talus, significant improvements were observed in all outcome measures (AOFAS, FAOS, and NRS) after an average follow-up of 50 months, indicating the efficacy of the HemiCAP treatment.

While no revisions of the HemiCAP were necessary, 41.9% of patients required additional surgeries, highlighting the importance of careful patient selection and information prior to the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mid-term results after treatment of complex talus osteochondral defects with HemiCAP implantation. Ebskov, LB., Hegnet Andersen, K., Bro Rasmussen, P., et al.[2020]

Osteochondritis dissecans (OCD) primarily affects the knee joint and involves the separation of bone fragments along with the cartilage, which can lead to joint issues.

The article reviews various causes and classification systems for OCD, along with diagnosis and treatment strategies, highlighting the importance of understanding this condition for effective management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osteochondritis dissecans of the distal femur and patella. Obedian, RS., Grelsamer, RP.[2019]

References

1. 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]

2. 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]

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

Use of Tetrahydrocannabinol and Cannabidiol Products in the Perioperative Period Around Primary Unilateral Total Hip and Knee Arthroplasty. [2021]

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

Antinociceptive and Anti-Inflammatory Properties of Cannabidiol Alone and in Combination with Standardized Bioflavonoid Composition. [2021]

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

Computational Approach Reveals Pronociceptive Potential of Cannabidiol in Osteoarthritis: Role of Transient Receptor Potential Channels. [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. England pubmed.ncbi.nlm.nih.gov

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

White matter integrity after cannabidiol administration for treatment resistant epilepsy. [2022]

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

Prevalence of Bilateral JOCD of the Knee and Associated Risk Factors. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Revision of Failed Osteochondritis dissecans Surgical Treatment: Case Report. [2023]

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

Internal Fixation of Unstable Osteochondritis Dissecans: Do Open Growth Plates Improve Healing Rate? [2019]

12. France pubmed.ncbi.nlm.nih.gov

Mid-term results after treatment of complex talus osteochondral defects with HemiCAP implantation. [2020]

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

Osteochondritis dissecans of the distal femur and patella. [2019]