Osteoarthritis of the knee is a common cause of pain in the US. The currently available medicines for knee osteoarthritis sometimes are not effective at relieving the pain or have unacceptable side effects. Thus, alternate pain relieving treatments are needed.

CBD, an active chemical from the hemp derived cannabis sativa plant, has received a lot of attention for its potential pain relieving properties, but there has been limited research to find out if topically applied CBD can decrease pain from knee osteoarthritis. CBD lacks the psychoactive effects seen with marijuana use, because it does not contain THC which is responsible for those effects in marijuana. It is legal to use CBD in the State of Tennessee (site of study).

The CBD Knee Study is sponsored by the University of Tennessee Health Science Center and is a collaborative effort between doctors at UT and Campbell Clinic. In the CBD Knee Study, the investigators are examining whether topically applied CBD dissolved in Castor Oil will relieve knee pain in persons with knee osteoarthritis.

Persons who take part in the study would need to come for study visits, fill out questionnaires about their health and knee pain, and would be asked to use the topical study oil on their knees. Taking part in the CBD Knee Study is voluntary.

Chronic pain is an enormous burden worldwide, impacting more than 30% of the population. Osteoarthritis (OA) is the most common form of joint disfunction and pain, affecting 33 million people in the United States. OA is a prominent cause of pain for older individuals, particularly knee pain. Due to the chronic and progressive nature of OA pain, many patients require long-term analgesic management. Non-steroidal anti-inflammatory drugs (NSAIDs), are commonly used to treat moderate pain from OA, but side effects and numerous potential drug interactions limit use in many individuals. Not surprisingly, opioids became a part of treatment for OA pain in the early 2000s, and have been commonly used for many years even though opioids are not recommend for use by osteoarthritis guideline committees due to their potential risk of misuse, abuse and overdose. With limitations on currently available treatments such as NSAIDs and opioids, the field is now exploring alternative analgesics to manage chronic osteoarthritis pain.

Medical marijuana and cannabis have long been used to treat chronic pain disorders and there is increasing interest to explore cannabinoids as alternate pain therapy. Cannabidiol (CBD), an active cannabinoid from hemp derived cannabis sativa, has garnered attention as a strong pharmaceutical candidate for analgesia. For example, in two recent systematic reviews, CBD was found to be beneficial for treating chronic pain and appeared to improve sleep and Quality of Life (QOL) for persons with chronic pain. CBD lacks the psychoactive effects seen with marijuana use, because it does not contain Δ9- tetrahydrocannabinol (THC) responsible for those effects in marijuana. These properties make CBD a clear candidate for an alternative treatment for chronic pain syndromes such as knee OA.

However, rigorous CBD research is limited in certain chronic pain populations such as persons with OA, but there are some data suggesting benefits. A cross-sectional study, in a large sample of individuals who used oral CBD for arthritis (n=428), showed that 83% reported a reduction in pain following CBD use, and 61% reported a reduction or cessation of other medications, including opioids (18%). There are, however, notable limitations in previous research on CBD for chronic pain that should be acknowledged. Many previous CBD research studies have focused primarily on orally administered CBD often at low doses, which undergoes first-pass metabolism in the liver, reducing bioavailability and potentially diminishing therapeutic effects. Additionally, much of the research relied on the use of over the counter (OTC) CBD products at lower doses, with unverified or untested purity and quality. Thus, additional research on CBD for pain relief is warranted in persons with knee OA. Topical CBD that avoids the first pass metabolism of oral routes has also been shown to reduce chronic pain. In a small randomized clinical trial (n=15) in patients with symptomatic peripheral neuropathy pain, topical CBD Oil use (250 mg / 3 fl. Oz - Higher Dose) resulted in a statistically significant reduction in intense pain, sharp pain and cold/itchy sensations compared with a placebo with no adverse events reported. In another placebo controlled crossover clinical trial in thumb basal joint osteoarthritis, patients had significant reductions in pain after 2 weeks of topical CBD (6.2 mg/ml BID - Lower Dose) administration vs. shea butter (placebo). Another pilot study (n=18) in individuals with hand OA found that topical transdermal CBD gel applied three times daily significantly decreased pain scores (p<0.0001), improved grip strength (p<0.0001), and alleviated stiffness. These findings suggest that topical CBD could represent a promising option for managing chronic localized pain conditions like knee OA. Despite this promising preliminary work, to our knowledge there are no studies using topical CBD at therapeutic doses to treat knee pain in persons with OA to definitively establish efficacy.

There is also a need for a vehicle to deliver the topical CBD dose to the knee area for maximal effect. Castor Oil is an excellent choice. Castor Oil is an odorless vegetable oil made from the seeds of the Castor plant. Castor Oil is already used as a vehicle to assist with delivery of FDA approved topical pain relief medications such as diclofenac sodium (NSAID) to the area of intended use. The main constituent of Castor Oil is ricinoleic acid, which may also have anti-inflammatory and analgesic effects. Thus, Castor Oil is a clear choice as a vehicle to deliver topical CBD to the site of pain in persons with knee OA.

Given healthcare challenges to manage chronic pain, including avoiding opioids because of their addictive potential, investigation of topically applied CBD dissolved in a vehicle such as Castor Oil may provide a promising alternative therapy for the reduction of OA pain of the knee, while having an exceptional safety profile. However, additional research on topical CBD+Castor Oil using rigorous study designs is needed to document efficacy and safety for the treatment of OA pain of the knee.

To address this issue, the investigators will conduct a pilot randomized crossover clinical trial to examine the analgesic efficacy of topical CBD+Castor Oil compared to a topical Castor Oil alone. 30 patients with OA pain of the knee will be randomized. The investigators anticipate 60 patients will sign consent and screen to randomize 30 patients.

SPECIFIC AIMS

Aim 1: Examine medication analgesic efficacy within subjects (n=30) in a balanced crossover design where each participant receives both treatments in randomized order with a 2-week washout period in between. Participants will be randomized to (1) CBD+Castor Oil followed by Castor Oil alone; or 2) Castor Oil alone followed by CBD+Castor Oil. Each oil will be used for a total of 1 month. Hypothesis 1: CBD+Castor Oil will have reduced knee pain scores compare to Castor Oil alone.

Aim 2: Examine changes in knee function, sleep, and knee Quality Of Life (QOL) by medication condition. Hypothesis 2: CBD+Castor Oil will have higher knee function, reduced sleep disturbance scores, and higher QOL than Castor Oil alone.

The investigators hypothesize that with adequate analgesic properties and low safety concerns, topical CBD+Castor Oil may be extremely useful to manage chronic OA knee pain while improving knee function, QOL, and sleep.

Inclusion Criteria:

1. Knee OA (grade 2-3 as measured by the Kellgren-Lawrence Classification)
2. OA knee pain on the Visual Analog Pain Scale > 4 in either knee
3. Receiving treatment at one of the eight Campbell Clinic Orthopaedics locations

Exclusion Criteria:

1. Other forms of arthritis such as psoriatic arthritis or rheumatoid arthritis due to different sources of inflammation in these conditions
2. Allergies to CBD or Castor Oil
3. Current opioid use
4. BMI of over 40
5. Those who cannot walk without an assistance device (e.g., walker)
6. Those who are currently on knee injections (i.e. cortisol or hyaluronic acid gel) for knee pain
7. Patients scheduled for a knee replacement in the next 3-6 months
8. Active cannabis or CBD use
9. Alcohol consumption > 21 alcoholic drinks each week
10. Active pregnancy, nursing, or actively planning a pregnancy
11. Active chronic liver or renal disease
12. Active depression/suicidality
13. Medications that interact with CBD in the liver that cannot be discontinued 14. Discretion of the Multiple Principal Investigators for concerns regarding noncompliance with the study intervention.

The study will prepare and distribute a dataset. Confidentiality of individual participants will be maintained with all releases of data. The final study analytical database will be processed according to HIPAA definitions for public data sharing. During this process, the participant data will be de-identified by using processes which include but are not limited to: removal of identifiers, translation of dates and ages to delta time values, and assignment of random study identifiers. Out of this process will be a series of de-identified data files representing the final analytical data set. These data files will be provided in a standard format that is readable across a variety of applications and operating system platforms. Documentation that will be provided along with the data sharing file that may include but is not limited to: data dictionary, data code book, valid variable ranges, the protocol, MOP, and any electronic versions of any paper forms that were used in data collection.