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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of oral CBD capsules in relieving pain in the upper arms, including the shoulders, elbows, or wrists. The researchers aim to determine if CBD capsules are more effective at easing pain than a placebo (a pill with no active ingredient) and if they are safe to use. Participants will take either CBD capsules or placebo capsules twice daily for four weeks and complete surveys about their pain and daily functioning. This trial suits individuals who have experienced musculoskeletal pain in their upper arms for at least three months and endure significant daily pain. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CBD is generally safe and well-tolerated by most people. Studies have not found any serious side effects from using CBD. Some participants experienced fatigue, changes in appetite or weight, and a few reported diarrhea.

Although CBD is often used for muscle and joint pain, strong evidence for its effectiveness in pain relief is lacking. This trial aims to determine if oral CBD can help with pain in the arms or hands. Based on previous research, participants can expect the treatment to be quite safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using cannabidiol (CBD) for musculoskeletal pain because it offers a new approach compared to traditional pain relievers like NSAIDs or opioids. Unlike these standard treatments, which often come with significant side effects and risk of dependency, CBD is derived from cannabis and is believed to have pain-relieving properties without the high or addiction potential. Additionally, CBD interacts with the body's endocannabinoid system, which is a different mechanism of action that could provide relief for those who haven't found success with other pain management options. This fresh perspective on pain treatment has the potential to provide a safer, more natural alternative for managing musculoskeletal discomfort.

What evidence suggests that CBD might be an effective treatment for musculoskeletal pain?

Research suggests that cannabidiol (CBD), which participants in this trial may receive as an oral treatment, may help ease muscle and joint pain. Studies have found that CBD can reduce pain and swelling, especially in long-term pain conditions. One study showed that medical cannabis, which includes CBD, significantly relieved pain for many patients. For hand and wrist arthritis, applying CBD to the skin has helped with pain. While data on oral CBD for arm and hand pain is limited, these findings indicate it might be worth exploring. ^{2 6 7 8 9}

Who Is on the Research Team?

Brent DeGeorge, MD, PhD

Principal Investigator

University of Virginia Department of Plastic Surgery

Are You a Good Fit for This Trial?

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

History of drug or substance abuse

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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