Category Archives: Arthritis

Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress

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Figure 1

“Growing evidence suggests that the endocannabinoid system, which includes the CB1 and CB2 G protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system, but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development.

This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types I and II diabetes, atherosclerosis, Alzheimer’s disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.

Cannabidiol (CBD) is the major nonpsychotropic cannabinoid compound derived from the plant Cannabis sativa, commonly known as marijuana…

Conclusions

Inflammation and oxidative stress are intimately involved in the genesis of many human diseases. Unraveling that relationship therapeutically has proven challenging, in part because inflammation and oxidative stress “feed off” each other. However, CBD would seem to be a promising starting point for further drug development given its anti-oxidant (although relatively modest) and anti-inflammatory actions on immune cells, such as macrophages and microglia. CBD also has the advantage of not having psychotropic side effects. Studies on models of human diseases support the idea that CBD attenuates inflammation far beyond its antioxidant properties, for example, by targeting inflammation-related intracellular signaling events. The details on how CBD targets inflammatory signaling remain to be defined.

The therapeutic utility of CBD is a relatively new area of investigation that portends new discoveries on the interplay between inflammation and oxidative stress, a relationship that underlies tissue and organ damage in many human diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085542/

Reassessment of the role of cannabinoids in the management of pain.

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“The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans.

 …to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS.

SUMMARY:

The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain.”

http://www.ncbi.nlm.nih.gov/pubmed/17873600

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials.

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“Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required.

In conclusion this systematic review of 18 recent good quality randomized trials demonstrates that cannabinoids are a modestly effective and safe treatment option for chronic non-cancer (predominantly neuropathic) pain. Given the prevalence of chronic pain, its impact on function and the paucity of effective therapeutic interventions, additional treatment options are urgently needed. More large scale trials of longer duration reporting on pain and level of function are required.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243008/

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

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“Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the ‘holy grail’ of endocannabinoid research.”

http://www.ncbi.nlm.nih.gov/pubmed/23155985

Inhibition of Human Neutrophil Chemotaxis by Endogenous Cannabinoids and Phytocannabinoids: Evidence for a Site Distinct from CB1 and CB2

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   “Here, we show a novel pharmacology for inhibition of human neutrophil migration by endocannabinoids, phytocannabinoids, and related compounds. The endocannabinoids virodhamine and N-arachidonoyl dopamine are potent inhibitors of N-formyl-l-methionyl-l-leucyl-l-phenylalanine-induced migration of human neutrophils…”

   “This study reveals that certain endogenous lipids, phytocannabinoids and related ligands are potent inhibitors of human neutrophil migration, and it implicates a novel pharmacological target distinct from cannabinoid CB1 and CB2 receptors; this target is antagonized by the endogenous compound N-arachidoloyl l-serine. These findings corroborate the emerging clinical and animal model data demonstrating that the nonpsychoactive phytocannabinoid, CBD and its structural analogs are effective in alleviating arthritis. Furthermore, our findings have implications for the potential pharmacological manipulation of elements of the endocannabinoid system for the treatment of various inflammatory conditions.”

http://molpharm.aspetjournals.org/content/73/2/441.long

Marijuana May Fight Lung Tumors – FoxNews

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   “…the active ingredient in marijuana may help combat lung cancer, new research suggests.

In lab and mouse studies, the compound, known as THC, cut lung tumor growth in half and helped prevent the cancer from spreading, says Anju Preet, PhD, a Harvard University researcher in Boston who tested the chemical. 

While a lot more work needs to be done, “the results suggest THC has therapeutic potential,” she tells WebMD. 

Moreover, other early research suggests the cannabis compound could help fight brain, prostate, and skin cancers as well, Preet says.”

Read more: http://www.foxnews.com/story/0,2933,266715,00.html

Read more: http://www.foxnews.com/story/0,2933,266715,00.html#ixzz2C1POR7Ap

High hopes for new marijuana drug

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Marijuana

“Researchers have developed a synthetic compound which gives the benefits of marijuana without the high.

US researchers are developing a marijuana-derived synthetic compound to relieve pain and inflammation without the mood-altering side effects associated with other marijuana based drugs.

Professor Sumner Burstein, from the University of Massachusetts Medical School in Worcester, presented his team’s findings at last week’s national meeting of the American Chemical Society in Boston.

He is hopeful about the potential of the synthetic compound to treat a variety of conditions, including chronic pain, arthritis and Multiple Sclerosis.

The synthetic compound is called ajulemic acid, and has a formula based on that of THC. It has already produced encouraging results in animal studies of pain and inflammation, and is currently being tested on humans.

Exactly how ajulemic acid works is still under investigation but it appears to suppress chemical mediators, such as prostaglandins and cytokines, known to cause inflammation.

“We believe the compound will replace aspirin and similar drugs in most applications because of its lack of toxic side effects”, said Professor Burstein, referring to extensive animal studies, as well as a safety trial of the compound conducted in France last year among 15 healthy volunteers.

No clinically adverse effects were reported, including gastrointestinal ulcers, which have been associated with other non-steroidal anti-inflammatory compounds such as aspirin and ibuprofen.

But most significantly, no mood-altering side effects were reported. With an increasing number of medically beneficial compounds being found in marijuana, such as THC and CBD, researchers have been searching for years for ways to utilise these therapeutically without their associated “high”. They have had little success until now.

“Some people want the high,” admits Professor Burstein. “But the medical community wants efficacy without this effect.”

As well as animal studies of their own that show the compound is as potent a painkiller as morphine, Professor Burstein notes other promising animal studies that have been published. In rodent models of rheumatoid arthritis, the compound prevented joint damage. Tests of MS in rats showed the drug relieves muscle stiffness associated with the disease.

It is now undergoing tests in Germany in a group of 21 patients with chronic pain who take ajulemic acid orally twice daily, in capsule form.

Depending on these results, which will be available in about six weeks, the researchers predict the synthetic compound could be on offer by prescription within two years.

It could also be a promising alternative to current drugs used to treat arthritis, such as COX-2 inhibitors. These have been linked to adverse side effects, including heart attacks and stroke.”

http://www.abc.net.au/science/articles/2002/08/26/656786.htm?fb_action_ids=460011707368809&fb_action_types=og.likes&fb_source=aggregation&fb_aggregation_id=288381481237582

Cannabis drug ‘fights pain without high’

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   “Scientists have developed a cannabis-based medicine which relieves chronic pain without any of the “high” normally associated with the drug.

They believe the discovery could pave the way for cannabis-based medication to become available by prescription within two years.

Much of the controversy surrounding the medicinal use of cannabis has centred on fears that it would be used solely for its mood-altering effects.

However, scientists at the University of Massachusetts in the United States say their discovery should help authorities to overcome these fears.

Dr Sumner Burstein and colleagues say early trials of the medication in animals and healthy patients have been promising.

The medication, called ajulemic acid or CT3, has been manufactured in laboratories.

It maximises the medicinal effects of tertrahydrocannabinol – the key ingredient of cannabis – without any of the mind-altering effects.

‘More effective’

In animal tests, this compound was found to be between 10 to 50 times more effective at reducing pain than tetrahydrocannabinol.

Those tests showed that ajulemic acid was very effective at preventing the joint damage associated with arthritis and relieving the muscle stiffness associated with multiple sclerosis.”

Read more: http://news.bbc.co.uk/2/hi/health/2207478.stm

Marijuana-Derived Compound Targets Pain, Inflammation

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   “Researchers are developing a marijuana-derived synthetic compound to relieve pain and inflammation without the mood-altering side effects associated with other marijuana based drugs.

  They say the compound could improve treatment of a variety of conditions, including chronic pain, arthritis and multiple sclerosis. Their findings were presented at the 224th national meeting of the American Chemical Society, the world’s largest scientific society.

   The compound, called ajulemic acid, has produced encouraging results in animal studies of pain and inflammation. It is undergoing tests in a group of people with chronic pain and could be available by prescription within two to three years, the researchers say.

 “We believe that [the compound] will replace aspirin and similar drugs in most applications primarily because of a lack of toxic side effects,” says Sumner Burstein, Ph.D., lead investigator in the study and a professor in the department of biochemistry and molecular pharmacology at the University of Massachusetts Medical School in Worcester. “The indications so far are that it’s safe and effective,” he added.”

Read more: http://www.sciencedaily.com/releases/2002/08/020822071026.htm

Suppression of human monocyte interleukin-1beta production by ajulemic acid, a nonpsychoactive cannabinoid.

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Abstract

   “Oral administration of ajulemic acid (AjA), a cannabinoid acid devoid of psychoactivity, reduces joint tissue damage in rats with adjuvant arthritis. Because interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha) are central to the progression of inflammation and joint tissue injury in patients with rheumatoid arthritis, we investigated human monocyte IL-1beta and TNFalpha responses after the addition of AjA to cells in vitro… Reduction of IL-1beta by AjA may help explain the therapeutic effects of AjA in the animal model of arthritis. Development of nonpsychoactive therapeutically useful synthetic analogs of Cannabis constituents, such as AjA, may help resolve the ongoing debate about the use of marijuana as medicine.”

http://www.ncbi.nlm.nih.gov/pubmed/12566094