cbd and joint pain

Cbd and joint pain

Enthusiasts of cannabidiol (better known as CBD) rave about the substance’s health benefits. Some small studies have shown that CBD could be a remedy for anxiety and help children with post-traumatic stress disorder get to sleep. The substance was even FDA-approved last year as a prescription drug to manage rare, severe forms of epilepsy.

What Is CBD, and Can It Help with Arthritis?

Don’t just buy the least expensive one on the shelf. There are lots of poor-quality CBD products on the market (some of which don’t contain the amount of CBD they claim, per these FDA warning letters).

2. Look for Signs of High-Quality CBD

“Cannabinoids can inhibit or excite the release of neurotransmitters [brain chemicals] and play a role in modulating the body’s natural inflammatory response, which are the two things we’re concerned about when talking about CBD for arthritis,” says Hervé Damas,MD, a Miami-based physician and founder of Grassroots Herbals, a CBD product company.

Currently recommended pharmacologic treatment options for the symptomatic management of osteoarthritis include non-steroidal anti-inflammatories (NSAIDs), low-dose steroids, and viscosupplementation. However, each of these modalities is fraught with side effects when used for long periods of time, and given the insidious time course of osteoarthritis, CBD may prove a useful drug for those with an aversion to other therapies. Additionally, the evidence for viscosupplementation relies on the results of controversial, randomized-controlled trials, and intra-articular preparations have notable contraindications to therapy. Therefore, it is reasonable to suggest that CBD is a safe, useful alternative or adjunct for the treatment of neuropathic joint pain due to secondary osteoarthritis. Osteoarthritis is a progressive disease that results in subchondral bone loss over the years, accelerated by a variety of environmental and genetic factors. In a study by Philpott et al. in 2017, osteoarthritis was induced in male Wistar rats via intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). In addition to its therapeutic effect caused by a decreased joint firing rate and an increased threshold for weight-bearing, the authors demonstrate a prophylactic benefit of 100-300 mcg of CBD as evidenced by a statistically significant reduction of MIA-induced joint pain at a later time point [12]. Despite a small sample size (n = 8), these data are promising and suggest a possible role in prolonging the time course of osteoarthritis, either to the onset of clinical symptoms or to the need for pharmacologic or operative intervention. Therefore, one practical application of cannabinoids including CBD is in the primary prevention of osteoarthritis, or in its preoperative use. In a 2015 study by Kogan et al., CBD enhanced the biochemical properties of healing rat mid-femoral fractures via stimulation of mRNA expression of Plod1 in primary osteoblast cultures, a mechanism well-understood to be involved in collagen cross-linking and bony stabilization [13]. For this reason, along with the evidence presented herein, the orthopedic community has taken interest in CBD, along with other cannabis products, as a potential adjunct for musculoskeletal disease treatment, both in the preoperative and postoperative period.

Clinical utility: cannabidiol

Review

Cannabis-based medicines have been employed in the orthopedic practice, though a lack of sufficient data precludes its widespread recommendation. A secondary literature review on cannabis-based therapy in orthopedics was conducted using a PubMed MeSH (MEDLINE) search: (“Cannabis”[Mesh]) and (“Fractures”[MeSH]) OR (“Arthroplasty”[MeSH]). The search yielded nine studies following the exclusion of two that did not meet inclusion criteria or were considered outside the realm of this study (Table  1 ). Additionally, Google Scholar was queried using the key phrases “cannabinoids, arthroplasty”, which yielded one more recent article by Runner et al. (2020) not found in the initial search.

CBD, the major nonpsychoactive component of cannabis, has undergone a bevy of research in murine model organisms, though there is scant, well-vetted evidence of its efficacy in humans. In a study by Malfait et al. in 2000, DBA/1 mice underwent a collagen-induced arthritis (CIA) by immunization with type II collagen (CII) in complete Freund’s adjuvant (CFA) [4]. CBD was then administered after the onset of clinical symptoms, resulting in diminished CII-specific proliferation, IFN-gamma production, and release of tumor necrosis factor. Incidentally, in a separate murine line, the same authors found that CBD was capable of blocking the lipopolysaccharide (LPS)-induced rise in serum tumor necrosis alpha [4]. A subsequent review by Stephen Straus highlighted the aforementioned findings and suggested that CBD is effective when dosed orally or intraperitoneally, noting that it followed a sharp dose-response curve that limits its efficacy range [5]. Thereafter in 2004, Sumariwalla et al. explored the potential antiarthritic effects of a novel, synthetic cannabinoid acid pegged Hebrew University-320 (HU-320). In a prospective manner, these authors immunized DBA/1 mice with bovine CII, injected intraperitoneal HU-320, and assessed the outcomes both clinically and histologically [6]. The results of systemic, daily administration of 1 and 2 mg/kg HU-320 “ameliorated” the established CII-induced arthritis, without any noticeable adverse psychotropic effects [6]. Therefore, these data indicate that cannabinoids such as CBD, in both an anti-inflammatory and immunosuppressive manner, have potent anti-arthritic effects with a subjectively diminished adverse risk profile.

Table 1

Secondly, a more recent exploration into the role of cannabinoids in the treatment of non-rheumatoid arthritis pain suggests that CBD binds to and activates an atypical receptor system entirely. In their article on a novel endogenous receptor called G-protein coupled receptor55 (GPR55), Schuelert and McDougall investigated whether or not the synthetic GPR55 agonist 0-1602, a CBD analog, alters joint nociception in a rat model subjected to acute joint inflammation [10]. The authors induced acute (24-hour) joint pain by injecting male Wistar rats with intra-articular preparations of 2% kaolin and 2% carrageenan. Using extracellular recordings from afferent nociceptive fibers, they found that peripheral administration of 0-1602 reduced the firing of afferent C fibers in response to mechanical rotation of the knee [10]. Though not explicitly translatable to stress-induced osteoarthritic changes in a human knee, this study highlights the role of cannabinoid receptors in joint nociception and suggests a potential relationship between CBD and relief of joint pain in a non-immune fashion. Further evidence for the anti-arthritic role of CBD stems from additional animal studies that evaluate its route of administration and anti-inflammatory effects. Similar to the work produced by Schuelert and McDougall, Hammell et al. investigated a topical CBD application in an attempt to avoid gastric diminution of the drug, hepatic first-pass metabolism, and to achieve greater plasma drug levels outright. The authors describe a favorable transdermal absorption profile when dosed in 0.6-6.2 mg/day, and note that topical CBD significantly reduced joint swelling, limb posture scores, and thickening of the synovial membrane in a dose-dependent manner. Additionally, immunohistochemical analysis of spinal cord and dorsal root ganglia revealed dose-dependent reductions of pro-inflammatory biomarkers, without a concomitant rise in behavior alteration to suggest a psychotropic effect [11]. In light of these data, there emerges a theme. In rodent models, CBD administration has proven anti-inflammatory effects, with a seemingly sharp dose-response peak, no evidence of neurocognitive side effects, and a histologic regression of arthritis in the short term.