“Cannabis has been used to treat pain for thousands of years.
However, since the early part of the 20th century, laws restricting cannabis use have limited its evaluation using modern scientific criteria. Over the last decade, the situation has started to change because of the increased availability of cannabis in the United States for either medical or recreational purposes, making it important to provide the public with accurate information as to the effectiveness of the drug for joint pain among other indications.
The major psychotropic component of cannabis is Δ9-tetrahydrocannabinol (THC), one of some 120 naturally occurring phytocannabinoids. Cannabidiol (CBD) is another molecule found in herbal cannabis in large amounts. Although CBD does not produce psychotropic effects, it has been shown to produce a variety of pharmacological effects. Hence, the overall effects of herbal cannabis represent the collective activity of THC, CBD and a number of minor components.
The action of THC is mediated by two major G-protein coupled receptors, cannabinoid receptor type 1 (CB1) and CB2, and recent work has suggested that other targets may also exist. Arachidonic acid derived endocannabinoids are the normal physiological activators of the two cannabinoid receptors.
Natural phytocannabinoids and synthetic derivatives have produced clear activity in a variety of models of joint pain in animals. These effects are the result of both inhibition of pain pathway signalling (mostly CB1) and anti-inflammatory effects (mostly CB2). There are also numerous anecdotal reports of the effectiveness of smoking cannabis for joint pain.
Indeed, it is the largest medical request for the use of the drug. However, these reports generally do not extend to regulated clinical trials for rheumatic diseases. Nevertheless, the preclinical and human data that do exist indicate that the use of cannabis should be taken seriously as a potential treatment of joint pain.”
“Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a non-euphoria producing constituent of cannabis that has the potential to relieve pain.
The aim of this study was to determine if CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy.
The therapeutic and prophylactic effects of peripheral CBD (100-300μg) were assessed. In end stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (p<0.0001; n=8). Acute, transient joint inflammation was reduced by local CBD treatment (p<0.0001; n=6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (p<0.0001; n=8), and was also found to be neuroprotective (p<0.05; n=6-8).
The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints.
These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.”
“This review discusses the role of the cannabinoid system in cartilage tissue and endeavors to establish if targeting the cannabinoid system has potential in mesenchymal stem cell based tissue-engineered cartilage repair strategies.
The review discusses the potential of cannabinoids to protect against the degradation of cartilage in inflamed arthritic joints and the influence of cannabinoids on the chondrocyte precursors, mesenchymal stem cells (MSCs).
We provide experimental evidence to show that activation of the cannabinoid system enhances the survival, migration and chondrogenic differentiation of MSCs, which are three major tenets behind the success of a cell-based tissue-engineered cartilage repair strategy.
These findings highlight the potential for cannabinoids to provide a dual function by acting as anti-inflammatory agents as well as regulators of MSC biology in order to enhance tissue engineering strategies aimed at cartilage repair.”
“Several studies in humans have reported that improved pain control is associated with exercise in a variety of painful conditions, including osteoarthritis, fibromyalgia, and neuropathic pain.
Despite the growing amount of experimental data on physical exercise and nociception, the precise mechanisms through which high-intensity exercise reduces pain remain elusive.
Since the glutamatergic system plays a major role in pain transmission, we firstly analyzed if physical exercise could be able to decrease glutamate-induced nociception through G-protein-coupled receptor (G-PCR) activation.
The second purpose of this study was to examine the effect of exercising upon phosphorylation of protein kinase A (PKA) isoforms induced by intraplantar (i.pl.) glutamate injection in mice.
Our results demonstrate that high-intensity swimming exercise decreases nociception induced by glutamate and that i.pl. or intrathecal injections of cannabinoid, opioid, and adenosine receptor antagonists, AM281, naloxone, and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), respectively, prevent this effect.
Furthermore, the peripheral A1 and opioid receptors, but not CB1, are also involved in exercise’s effect. We also verified that glutamate injection increases levels of phosphorylated PKA (p-PKA). High-intensity swimming exercise significantly prevented p-PKA increase.
The current data show the direct involvement of the glutamatergic system on the hyponociceptive effect of high-intensity swimming exercise as well as demonstrate that physical exercise can activate multiple intracellular pathways through G-PCR activation, which share the same endogenous mechanism, i.e., inhibition of p-PKA.”
“Cannabinoids have shown to reduce joint damage in animal models of arthritis and reduce matrix metalloproteinase expression in primary human osteoarthritic (OA) chondrocytes.
Chondrocytes from OA joints were shown to express a wide range of cannabinoid receptors even in degenerate tissues, demonstrating that these cells could respond to cannabinoids.
Cannabinoids designed to bind to receptors inhibiting the catabolic and pain pathways within the arthritic joint, while avoiding psychoactive effects, could provide potential arthritis therapies.
Cannabinoids were originally derived from the cannabis plant, Cannabis sativa, which has been used medicinally and recreationally for many years because of its anti-inflammatory, analgesic, and psychoactive properties.”
“Marijuana, the common name for Cannabis sativa, is a widely distributed hemp plant whose dried flowering tops and leaves have been used for medicinal purposes for 12,000 years by some estimates.
The article by Malfaitet al. in this issue of PNAS is relevant to the question of whether such traditional uses of marijuana could be clinically justifiable today.
It is conceivable that marijuana contains a series of cannabinoids that, in the aggregate, could alleviate arthritis as implied in the present report, yet remain well tolerated.
Remarkably, the claim that marijuana does so also was made 4,000 years ago by the Chinese emperor Shen-nung whose pharmacobotanical compendium, the Pen-ts’ao Ching, concluded that cannabis “undoes rheumatism””
“Cannabinoids have been reported to have anti-inflammatory effects and reduce joint damage in animal models of arthritis.
This suggests a potential therapeutic role in arthritis of this group of compounds.
Cannabinoids were studied to determine whether they have direct effects on chondrocyte metabolism resulting in cartilage protection.
Synthetic cannabinoids, R-(+)-Win-55,212 (Win-2) and S-(-)-Win-55,212 (Win-3) and the endocannabinoid, anandamide, were investigated on unstimulated or IL-1-stimulated nitric oxide (NO) production in bovine articular chondrocytes as well as on cartilage proteoglycan breakdown in bovine nasal cartilage explants.
Win-2 significantly inhibited (P < 0.05) NO production in chondrocytes at 1-10 microM concentrations. The combined CB(1) and CB(2) cannabinoid receptor antagonists, AM281 and AM630, respectively, at 100 microM did not block this effect, but instead they potentiated it. Anandamide and Win-2 (5-50 microM) also inhibited the release of sulphated glycosaminoglycans in bovine cartilage explants.
The results suggest that some cannabinoids may prevent cartilage resorption, in part, by inhibiting cytokine-induced NO production by chondrocytes and also by inhibiting proteoglycan degradation.”
“Cannabinoids have analgesic, immunomodulatory and anti-inflammatory properties and attenuate joint damage in animal models of arthritis.
Chondrocytes appeared to constitutively express cannabinoid receptors CB1 and CB2.
It is concluded that biologically stable synthetic cannabinoids protect cartilage matrix from degradation induced by cytokines and this effect is possibly CB-receptor mediated and involves effects on prostaglandin and nitric oxide metabolism.”