CBD for Musculoskeletal Pain

Overseen By Lindsey Wilkin, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Brent DeGeorge

Must not be taking: Coumadin, Corticosteroids, Opioids, Cannabis

Disqualifiers: Severe organ disease, Mental illness, Substance abuse, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn about the use of cannabidiol (CBD) capsules as a treatment for musculoskeletal pain. CBD is commonly being used as an over-the-counter treatment for musculoskeletal pain. Clinical trials have demonstrated a pain-relief benefit for hand and wrist osteoarthritis with topical CBD, however patients prefer oral CBD and no clinical trial has been performed to establish efficacy of oral CBD in humans for upper extremity musculoskeletal pain. The main questions it aims to answer are: Is CBD more effective than placebo at relieving pain for upper extremity musculoskeletal pain ? Is CBD safe for participants with upper extremity musculoskeletal pain? Participants will: take 4 weeks of daily CBD capsules take 4 weeks of daily placebo capsules answer surveys about how they are feeling and functioning. Participants will \[describe the main tasks participants will be asked to do, interventions they'll be given and use bullets if it is more than 2 items\].

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications, including those that are substrates of specific enzymes like CYP3A4, CYP2C19, CYP2C8, CYP2C9, CYP1A2, and CYP2B6, within 14 days before the study. Additionally, participants must not use opioids, topical analgesics, or any CBD products during the study.

What data supports the effectiveness of the drug Cannabidiol (CBD) for musculoskeletal pain?

Research suggests that CBD may help with chronic pain management, as seen in studies with fibromyalgia patients who reported improvements in pain and other symptoms. Additionally, CBD has shown potential in reducing pain behaviors in animal models and promoting tissue regeneration, which could be beneficial for musculoskeletal conditions. ^{1 2 3 4 5}

Is CBD generally safe for humans?

Research shows that CBD is generally well-tolerated in humans, with most side effects being minor. However, some serious adverse reactions have been reported, especially when used with other medications like antiepileptics. It's important to discuss CBD use with a healthcare provider to ensure safety. ^{1 2 6 7 8}

How does the drug CBD differ from other treatments for musculoskeletal pain?

CBD is unique because it is a natural compound from the cannabis plant that not only helps reduce pain and inflammation but also promotes tissue regeneration, which is not a common feature of other pain treatments. It is considered safe and well-tolerated, with no serious side effects reported. ^{1 2 4 9 10}

Research Team

Brent DeGeorge, MD, PhD

Principal Investigator

University of Virginia Department of Plastic Surgery

Eligibility Criteria

This trial is for individuals experiencing upper extremity musculoskeletal pain, such as arm and muscle pain. Participants will take daily CBD capsules or placebo for 4 weeks each and complete surveys about their pain and function.

Inclusion Criteria

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study

I have been experiencing pain for 3 months or more.

Exclusion Criteria

My liver function tests are significantly abnormal.

Subjects who are incarcerated

I have used joint injections within the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either CBD or placebo capsules twice daily for 4 weeks, followed by a crossover to the other condition for another 4 weeks

8 weeks

Weekly visits (in-person or virtual) for monitoring and surveys

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Cannabidiol (CBD)

Trial Overview The study tests the effectiveness of oral CBD capsules compared to a placebo in relieving upper extremity musculoskeletal pain. It's designed to see if taking CBD every day is more helpful than taking a pill with no active ingredients.

Participant Groups

Group I: Oral CBD Experimental Treatment 1 Intervention

Oral CBD 25 mg capsules taken twice each day for 4 weeks.

Group II: Placebo Placebo Group 1 Intervention

Oral placebo capsules taken twice each day for 4 weeks

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?

Brent DeGeorge

Lead Sponsor

Trials

2

Recruited

200+

The Plastic Surgery Foundation

Collaborator

Trials

11

Recruited

1,300+

Findings from Research

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]

Cannabidiolic acid (CBDA) demonstrated significant anti-hyperalgesia and anti-inflammatory effects in a rat model when administered before inflammation, indicating its potential as a more potent alternative to cannabidiol (CBD).

The study found that combining low doses of CBDA and THC, which were ineffective alone, resulted in enhanced anti-hyperalgesia and reduced inflammation, suggesting a synergistic effect between these compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of cannabidiolic acid and ∆9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain. Rock, EM., Limebeer, CL., Parker, LA.[2018]

In a study of 28 patients with chronic neck or back pain, a combination of cannabidiol (CBD) and Δ9-THC was found to be well tolerated, with most side effects being mild, such as nausea and fatigue.

Patients experienced significant reductions in pain scores with higher doses (1.0 mL and 1.5 mL twice daily), achieving reductions of 28.8% and 34.1% respectively, indicating the efficacy of this treatment for chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Efficacy of a 10:25 Preparation of Δ9-Tetrahydrocannabinol and Cannabidiol for Treatment of Chronic Back or Neck Pain: A Multiple-Dose Escalation Study. Glare, P., Chye, R., Bloch, M., et al.[2023]

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]

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]

In a study involving 32 dogs with canine atopic dermatitis, treatment with a mix of CBD and CBDA significantly reduced pruritus (itchiness) scores at 14 and 28 days, indicating its potential effectiveness in alleviating itching associated with the condition.

However, there was no significant improvement in the overall severity of skin lesions as measured by the CADESI-04 score, suggesting that while CBD/CBDA may help with itching, it does not address the skin lesions themselves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a mixed cannabidiol and cannabidiolic acid based oil on client-owned dogs with atopic dermatitis. Loewinger, M., Wakshlag, JJ., Bowden, D., et al.[2022]

References

1. 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]

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

Cannabidiol Use for Fibromyalgia: Prevalence of Use and Perceptions of Effectiveness in a Large Online Survey. [2021]

3. Ireland pubmed.ncbi.nlm.nih.gov

Cannabidiol microinjection into the nucleus accumbens attenuated nociceptive behaviors in an animal model of tonic pain. [2022]

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

Cannabidiol for musculoskeletal regenerative medicine. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Effect of cannabidiolic acid and ∆9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tolerability and Efficacy of a 10:25 Preparation of Δ9-Tetrahydrocannabinol and Cannabidiol for Treatment of Chronic Back or Neck Pain: A Multiple-Dose Escalation Study. [2023]

7. 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]

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

Pharmacovigilance of unlicensed cannabidiol in European countries. [2023]

9. England pubmed.ncbi.nlm.nih.gov

The effect of a mixed cannabidiol and cannabidiolic acid based oil on client-owned dogs with atopic dermatitis. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Myorelaxant Effect of Transdermal Cannabidiol Application in Patients with TMD: A Randomized, Double-Blind Trial. [2020]