Immunoactive cannabinoids: Therapeutic prospects for marijuana constituents

Posted on August 1, 2016 by David

“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””

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC34030/

Characterization of delta9-tetrahydrocannabinol and anandamide antinociception in nonarthritic and arthritic rats.

Posted on August 1, 2016 by David

“The hypothesis was tested that THC and anandamide elicit antinociception in the paw pressure test, and that arthritic rats would exhibit a different response.

THC and anandamide appear to release an as yet unknown endogenous opioid, because naloxone significantly blocked their effects.

This study indicates that anandamide and THC may act at different receptor sites to modulate endogenous opioid levels in mechanical nociception.”

http://www.ncbi.nlm.nih.gov/pubmed/9610941

Effects of cannabinoids on nitric oxide production by chondrocytes and proteoglycan degradation in cartilage.

Posted on August 1, 2016 by David

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/15670582

Arthritis and cannabinoids: HU-210 and Win-55,212-2 prevent IL-1alpha-induced matrix degradation in bovine articular chondrocytes in-vitro.

Posted on August 1, 2016 by David

“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.”

http://www.ncbi.nlm.nih.gov/pubmed/16536902

Cannabinoids: novel therapies for arthritis?

Posted on August 1, 2016 by David

“A key feature of osteoarthritis and rheumatoid arthritis is the loss of articular cartilage.

Cartilage breakdown is mediated by complex interactions of proinflammatory cytokines, such as IL-1, inflammatory mediators, including nitric oxide and prostaglandin E(2), and proteases, including matrix metalloproteinases and aggrecanases, such as ADAMTS-4 and -5.

Cannabinoids have been shown to reduce joint damage in animal models of arthritis.

They have also been shown to prevent IL-1-induced matrix breakdown of collagen and proteoglycan, indicating that cannabinoids may mediate chondroprotective effects.

Cannabinoids produce their effects via several cannabinoid receptors and it is important to identify the key cannabinoids and their receptors that are involved in chondroprotection.

This review aims to outline the current and future prospects of cannabinoids as anti-arthritic therapeutics, in terms of their ability to prevent cartilage breakdown.”

http://www.ncbi.nlm.nih.gov/pubmed/22530636

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

Posted on April 19, 2016 by David

Image result for Curr Clin Pharmacol.

“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

Cannabinoid WIN‑55,212‑2 mesylate inhibits ADAMTS‑4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan‑1.

Posted on April 16, 2016 by David

“A central feature of osteoarthritis (OA) is the loss of articular cartilage, which is primarily attributed to cartilage breakdown.

Accumulating evidence also suggests that cannabinoids have chondroprotective effects.

In conclusion, to the best of our knowledge, the present study provides the first in vitro evidence supporting that the synthetic cannabinoid WIN‑55 inhibits ADAMTS‑4 activity in unstimulated and IL‑1β‑stimulated human OA articular chondrocytes by decreasing the mRNA stability/expression of syndecan‑1 via CB2.

This suggests a novel mechanism by which cannabinoids may prevent cartilage breakdown in OA.

In addition, it also provides novel insights into the pharmacological effects of synthetic cannabinoids on OA.” http://www.ncbi.nlm.nih.gov/pubmed/27082728

“Chondroprotective: A specific compound or chemical that delays progressive joint space narrowing characteristic of arthritis and improvesthe biomechanics of articular joints by protecting chondrocytes.” http://medical-dictionary.thefreedictionary.com/chondroprotective

Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain.

Posted on June 13, 2015 by David

“The levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol.

In this study, we investigated the role of the endocannabinoid system (ECS) in the emotional and cognitive alterations associated with osteoarthritis pain.

Changes found in these biomarkers of the ECS correlated with pain, affective and cognitive symptoms in these patients.

The ECS plays a crucial role in osteoarthritis and represents an interesting pharmacological target and biomarker of this disease.”

http://www.ncbi.nlm.nih.gov/pubmed/26067584

http://www.thctotalhealthcare.com/category/osteoarthritis/

The type 2 cannabinoid receptor regulates susceptibility to osteoarthritis in mice.

Posted on May 6, 2015 by David

“The aim of this study was to evaluate the role of the type 2 cannabinoid receptor (Cnr2) in regulating susceptibility to osteoarthritis in mice.

These studies demonstrate that the Cnr2 pathway plays a role in the pathophysiology of osteoarthritis in mice and shows that pharmacological activation of CB2 has a protective effect.

Further studies of the role of cannabinoid receptors in the pathogenesis of osteoarthritis in man are warranted.”

http://www.ncbi.nlm.nih.gov/pubmed/25937028

http://www.thctotalhealthcare.com/category/osteoarthritis/

Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

Posted on March 3, 2015 by David

“Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics…

Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25730180

http://www.thctotalhealthcare.com/category/osteoarthritis/