Arthritis

Literature Discussion

The literature discussion is an overview of the published results from scientific studies investigating if and how cannabinoids can be beneficial in the treatment of Arthritis. The overview will be updated regularly to ensure the newest and most accurate information.

CB2 plays a role in the development of osteoarthritis.
In a paper by Sophocleous et al., mice genetically lacking CB2 were shown to have more severe experimentally induced osteoarthritis compared to control mice.5 Also, mice lacking CB2 had more severe naturally occurring osteoarthritis than control mice. This proposes that CB2 plays a role in the development of osteoarthritis and that CB2 activation may shield against osteoarthritis.

CBD may block disease progression.
In a paper by Malfait et al.6, disease progression was effectively blocked by a CBD dose of 5 mg/kg per day intraperitoneally (i.p.; substance injection to the peritoneum (body cavity)) or 25 mg/kg per day orally in mice with collagen-induced arthritis. Also, joint damage, lymphocyte proliferation as well as IFNγ and TNF expression were suppressed after CBD administration.

The usefulness of transdermal application of CBD
Hamell Et. al.7, investigated the usefulness of transdermal CBD in inflammation, pain, and evaluated side effects using a rat model of arthritis. The study found that inflammation and pain-related behaviors in arthritis were diminished when administrating transdermal CBD without obvious side effects.

CBD may suppress T cell function
Kaplan et al.8, discussed that cannabidiol (CBD) is one of the most common cannabinoids found in Cannabis Sativa. It does not have a high affinity for either the CB1 or CB2 cannabinoid receptors. Similar to other cannabinoids, it was shown that CBD suppressed attacks from the immune system (psoriasis and rheumatoid arthritis). The data of this study suggest that CBD suppresses T cell function and that CB1 and/or CB2 play a critical role in the magnitude of the In vitro Anti-SRBC IgM AFC.

CBD may have an anti-inflammatory effect
In a review article by Bruni et al.9, it was described that localized symptoms such as dermatological conditions and arthritis can potentially be treated through topical administration. Also, capsaicin patches have been suggested as a second-line treatment to relieve peripheral neuropathic pain. CBD was shown to alleviate arthritic pain-related behavior and have an anti-inflammatory effect without noticeable high-brain-center psychoactive effects. Also, CBD was found to reduce knee-joint swelling by using a dose of 6.2 mg/day, and that increasing the dose to 62 mg/day did not enhance the effect. In the same arthritic model, oral administration of CBD has been shown to result in poorer absorption compared to transdermal administration.

Collagen involvement in symptom relief and joint damage
Lonza, n.d & Lonza. 10, discussed that a small intake of oral UC II undenatured type II collagen boosts the production of key cells and cytokines connected with the induction of oral tolerance while diminishing arthritis symptoms. In vitro it was demonstrated that IL-10, one of the anti-inflammatory cytokines is involved in diminishing the destructive effects of TNF-alpha. The amount of TNF-alpha cytokine has been shown to be higher in osteoarthritis that harms chondrocyte survival and cartilage function. Bagchi and colleagues have shown that UC II undenatured type II collagen has biologically active epitopes to trigger oral tolerance. Further, research shows that the undenatured type II collagen is involved in symptom relief and protects against joint damage.

Cannabinoids in transdermal combination therapy
In an article by Stinchcomb et al.11, it was aimed to measure the amount of the in-vitro human skin transdermal flux of THC, CBD, and CBN due to their potential for transdermal combination therapy. The results showed that a lower heat of fusion and higher calculated relative thermodynamic activity was observed for CBN compared to CBD. The transdermal flux of Delta8-THC and CBD were enhanced by ethanol concentrations of 30 to 33% and tissue concentrations of CBN were significantly lower than for Delta8-THC. Lag times for CBN were shown to be longer than for CBD, and the permeabilities of CBD and CBN were shown to be 10-fold higher compared to Delta8-THC. As all three compounds have significant flux levels, further studies will be conducted on combinations of these cannabinoids using ethanol for the formulation of transdermal patches both in vitro and in vivo.

Bioavailability of CBD application
Paudel Et. al.12, aimed to evaluate nasal and transdermal permeation using rats and guinea pigs, respectively. Intranasal delivery of CBD showed a bioavailability of 34-46% with CBD being absorbed within 10 minutes. Polyethylene glycol formulation in rats showed a bioavailability of 100% and the use of enhancers did not improve bioavailability. Transdermal gel application in guinea pigs showed that the steady-state plasma concentration of CBD was sufficiently high for this administration route for CBD to be considered beneficial for treating chronic pain. Furthermore, it was demonstrated that with the use of enhancers, the steady-state concentration of CBD was increased by 3.7-fold. This shows that CBD could be successfully administered intranasally or transdermally.