SF Scientists: Marijuana Fights Cancer

(NBC Bay Area) “The “medical” bit of medical marijuana may be legitimate after all: Turns out a component of cannabis fights cancer, according to research.

Scientists at California Pacific Medical Center found that cannabidiol, or CBD, has the ability to “turn off” the DNA that causes “breast and other types of cancers” to metastasize, according to the San Francisco Chronicle.

“If this plant were discovered in the Amazon today, scientists would be falling all over each other to be the first to bring it to market,” said Dr. Donald Abrams, chief of oncology at the University of California San Francisco, which has also found science behind marijuana’s efficacy.

The drug “has been shown to reduce pain and nausea” in cancer patients, the newspaper reported. AIDS patients also swear by cannabis for its ability to allow them to eat, sleep and otherwise function.

Turns out that cannabidiol has none of the psychotropic effects of marijuana as a whole, according to the newspaper.”

http://m.nbcbayarea.com/nbcbayarea/pm_108022/contentdetail.htm?contentguid=DXQ0PNfC

Cannabinoids, Endocannabinoids, and Related Analogs in Inflammation.

“This review covers reports published in the last 5 years on the anti-inflammatory activities of all classes of cannabinoids, including phytocannabinoids such as tetrahydrocannabinol and cannabidiol, synthetic analogs such as ajulemic acid and nabilone, the endogenous cannabinoids anandamide and related compounds, namely, the elmiric acids, and finally, noncannabinoid components of Cannabis that show anti-inflammatory action. It is intended to be an update on the topic of the involvement of cannabinoids in the process of inflammation. A possible mechanism for these actions is suggested involving increased production of eicosanoids that promote the resolution of inflammation. This differentiates these cannabinoids from cyclooxygenase-2 inhibitors that suppress the synthesis of eicosanoids that promote the induction of the inflammatory process.”

 

“INTRODUCTION

This review is intended to be an update on the topic of the involvement of cannabinoids in the process of inflammation. Other reviews cover certain aspects of this subject and the reader is referred to them for a discussion of earlier reports. In this review are reports published in the last 5 years on the activities of all classes of cannabinoids, including the endogenous cannabinoids such as anandamide, related compounds such as the elmiric acids (EMAs), and noncannabinoid components of Cannabis that show anti-inflammatory action. An interesting recently published example of the latter one is caryophyllene, an abundant component of Cannabis oil that shows anti-inflammatory activity and has high affinity for cannabinoid receptor 2 (CB2; 5).”

 

“Phytocannabinoids: Tetrahydrocannabinol and Cannabidiol”

 

“PLANT PREPARATIONS AND NONCANNABINOID CONSTITUENTS OF CANNABIS”

“Cannabis sativa is a complex botanical, and it is not unlikely that the therapeutic benefits of marijuana are due to some of the more than 60 cannabinoids and 200–250 noncannabinoid constituents of the plant. One noncannabinoid, the geranylated flavone cannflavin A (Fig. 5), is 30 times more potent than aspirin as an inhibitor of prostaglandin E2 . These potentially important findings have been overlooked, as most attention in marijuana research has been directed to the analgesic effects of the plant and to mechanisms of psychoactivity. A further example that this line of inquiry has remained dormant is a series of overlooked observations, which demonstrate potent anti-inflammatory actions of a crude marijuana extract and of the nonpsychoactive Cannabis constituents, CBD, cannabinol, and cannabichromene in the carrageenan paw edema model of acute inflammation in rats. Volatile oil products of the plant also have biological activity. Thus, pyrolysis products may add to the therapeutic properties of smoked marijuana. Several of the most abundant cannabinoid and noncannabinoid constituents of C. sativa are nonpsychoactive.”

“Flavonoids are ubiquitous plant phenolic compounds that consist of two aromatic rings linked by a three carbon bridge. They are attracting interest because of their antioxidant, antitumor, anti-inflammatory, and antimicrobial activities. The flavone luteolin, a constituent of C. sativa, is also found in spices and in vegetables such as celery and green pepper. When added to peripheral blood mononuclear cells in vitro, luteolin suppresses production of the inflammatory cytokines TNFα, IL-1b, and IL-6, actions that relate to a selective reduction in numbers of monocytes. Perhaps more importantly, luteolin inhibits growth of Plasmodium falciparum in vitro and protects against induction of colon cancer in mice.”

“CONCLUSIONS

Possibly the very earliest literature reference on Cannabis describes its use as an anti-inflammatory agent. The Chinese emperor Shen-nung (ca. 2000 B.C.), in a work called Pen-ts’ao Ching, noted many of the effects of Cannabis in humans. Among other properties, it was claimed that cannabis “undoes rheumatism”, suggesting possible anti-inflammatory effects. The reports described in this review of the current literature provide support for the claims made by the ancient Chinese healers. These more recent publications include relief from chronic neuropathic pain, fibromyalgia, rheumatoid arthritis, and postoperative pain. In addition, a large body of preclinical data on all classes of cannabinoids, including the endogenous examples, point to a variety of therapeutic targets for cannabinoids and important roles for the endocannabinoids in the physiology of inflammation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664885/

Endocannabinoid overactivity and intestinal inflammation

Abstract

“Cannabinoid receptors of type 1 and 2 (CB1 and CB2), endogenous ligands that activate them (endocannabinoids), and mechanisms for endocannabinoid biosynthesis and inactivation have been identified in the gastrointestinal system. Activation of CB1 receptors by endocannabinoids produces relaxation of the lower oesophageal sphincter and inhibition of gastric acid secretion, intestinal motility, and fluid stimulated secretion. However, stimulation of cannabinoid receptors impacts on gastrointestinal functions in several other ways. Recent data indicate that the endocannabinoid system in the small intestine and colon becomes over stimulated during inflammation in both animal models and human inflammatory disorders. The pathological significance of this “endocannabinoid overactivity” and its possible exploitation for therapeutic purposes are discussed here.”

 

“The endocannabinoid system of the gastrointestinal tract includes not only cannabinoid receptors but also endogenous agonists of these receptors, as well as mechanisms for their biosynthesis and inactivation”

 

“The main psychotropic constituent of the plant Cannabis sativa and marijuana, Δ9‐tetrahydrocannabinol, exerts its pharmacological effects by activating two G protein coupled cannabinoid receptors.1These are the CB1 receptor, present in central and peripheral nerves (including the human enteric nervous system), and the CB2 receptor, expressed abundantly in immune cells. In rodents, CB1 receptor immunoreactivity has been detected in discrete nuclei of the dorsovagal complex (involved in emesis), and in efferents from the vagal ganglia and in enteric (myenteric and submucosal) nerve terminals where they inhibit excitatory (mainly cholinergic) neurotransmission. In vivo pharmacological studies have shown that activation of CB1 receptors reduces emesis, produces inhibition of gastric acid secretion8 and relaxation of the lower oesophageal sphincter (two effects that might be beneficial in the treatment of gastro‐oesophageal reflux disease), and inhibits intestinal motility and secretion. Consistent with immunohistochemical data showing that CB2 receptors are particularly evident in colonic tissues from patients with inflammatory bowel diseases (IBD), evidence suggests that CB2 inhibits intestinal motility during certain pathological states.1″

 

“…endocannabinoids convey protection from enteric hypersecretory states (for example, cholera toxin induced diarrhoea), which is in agreement with anecdotal reports from folk medicine on the use of Cannabis sativa in the treatment of diarrhoea.

 

“Overactivity of the endocannabinoid system is becoming a well established concept in human intestinal conditions with an inflammatory component”

   

“The inhibitory effects of cannabinoids on intestinal inflammation, as well as on intestinal motility and secretory diarrhoea, observed in preclinical studies, increase the potential for their use in the treatment of IBD”

  

“There is great potential for the development of new therapeutic agents against intestinal inflammation from the endocannabinoid system”

 

“Conclusions: new therapies for the treatment of IBD from the endocannabinoid system”

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856409/

Targeting the endocannabinoid system: to enhance or reduce?

Abstract

“As our understanding of the endocannabinoids improves, so does the awareness of their complexity. During pathological states, the levels of these mediators in tissues change, and their effects vary from those of protective endogenous compounds to those of dysregulated signals. These observations led to the discovery of compounds that either prolong the lifespan of endocannabinoids or tone down their action for the potential future treatment of pain, affective and neurodegenerative disorders, gastrointestinal inflammation, obesity and metabolic dysfunctions, cardiovascular conditions and liver diseases. When moving to the clinic, however, the pleiotropic nature of endocannabinoid functions will require careful judgement in the choice of patients and stage of the disorder for treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/18446159

Cannabinoids in intestinal inflammation and cancer.

Abstract

“Emerging evidence suggests that cannabinoids may exert beneficial effects in intestinal inflammation and cancer. Adaptive changes of the endocannabinoid system have been observed in intestinal biopsies from patients with inflammatory bowel disease and colon cancer. Studies on epithelial cells have shown that cannabinoids exert antiproliferative, antimetastatic and apoptotic effects as well as reducing cytokine release and promoting wound healing. In vivo, cannabinoids – via direct or indirect activation of CB(1) and/or CB(2) receptors – exert protective effects in well-established models of intestinal inflammation and colon cancer. Pharmacological elevation of endocannabinoid levels may be a promising strategy to counteract intestinal inflammation and colon cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/19442536

Brain’s own cannabis compound protects against inflammation

“Some clinical studies have indicated that marijuana or its active cannabinoid ingredient alleviates symptoms of the inflammatory disease multiple sclerosis (MS). Also, researchers have found that the brain’s natural “endocannabinoids” are released after brain injury and are believed to alleviate neuronal damage. However, scientists have not understood how such substances act within the brain’s own immune system.

 Now, experiments by Oliver Ullrich and colleagues have pinpointed how one of the brain’s endocannabinoids protects neurons from inflammation after such damage. They say their studies could lead to new drugs to treat the inflammation and brain degeneration from MS or other such disorders.

In an article in the January 5, 2006, issue of Neuron, the researchers reported experiments showing how the endocannabinoid anandamide (AEA) protects brain cells from inflammation. Such a role in the brain’s immune system is distinct from cannabinoids’ effects on neuronal signaling that produce the behavioral effects of marijuana.”

http://www.bio-medicine.org/biology-news/Brains-own-cannabis-compound-protects-against-inflammation-2810-1/

Pot Chemical May Curb Inflammation – WebMD

“Marijuana’s active ingredient may curb inflammation and help treat skin allergies.

That news comes from researchers including Meliha Karsak, PhD, and Thomas Tuting, MD, of Germany’s University of Bonn.

Marijuana’s key compound, THC, is a type of chemical called a cannabinoid. The brain contains two types of cannabinoid receptors.

Karsak and colleagues studied mice born with or without cannabinoid receptors. The mice wore ear tags to identify them; those ear tags contained nickel.

The mice without cannabinoid receptors were particularly likely to have allergic skin reactions to the nickel in the ear tags.

The scientists reasoned that the mice’s allergies may have been linked to their lack of cannabinoid receptors.

Karsak’s team tested that theory in several experiments.

First, they turned off cannabinoid receptors in healthy mice. Those mice then became more likely to develop skin inflammation near their nickel ear tags.

Next, the researchers exposed other mice with cannabinoid receptors to a skin irritant. Some of the mice got THC shots after being exposed to the irritant. Others got a THC skin lotion before and after exposure to the irritant.

The THC shot and lotion both helped soothe the mice’s inflamed skin.

“If we dabbed THC solution onto the animals’ skin shortly before and after applying the allergen, a lot less swelling occurred than normal,” Tuting says in a University of Bonn news release.

In the journal Science, the researchers write that their study “strongly suggests” that the body’s cannabinoid system can help tame inflammation and that THC skin lotions have “promising potential” for treating skin allergies caused by contact with irritating chemicals.

However, the researchers didn’t test the THC lotion on skin allergies in people.”

http://www.webmd.com/allergies/news/20070607/pot-chemical-may-curb-inflammation

“Attenuation of allergic contact dermatitis through the endocannabinoid system…These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin and suggest a target for therapeutic intervention.”  http://www.ncbi.nlm.nih.gov/pubmed/17556587

Why Cannabis Stems Inflammation

“Cannabis has long been accredited with anti-inflammatory properties. ETH Zurich researchers, however, have now discovered that it is not only the familiar psychoactive substances that are responsible for this; a compound we take in every day in vegetable nutriment also plays a significant role.

People not only rate cannabis sativa L. highly because of its intoxicating effects; it has also long been used as a medicinal plant. Although the plant has been scrutinized for years, surprising new aspects keep cropping up. For example, researchers from ETH Zurich and Bonn University examined a component in the plant’s essential oil that until then had largely been ignored and found it to have remarkable phar- macological effects. The findings open up interesting perspectives, especially for the prevention and treatment of inflammations.

The hemp plant contains over 450 different substances, only three of which are responsible for its intoxicating effect. They activate the two receptors in the body CB1 and CB2. Whilst the CB1 receptor in the central nervous system influences perception, the CB2 receptor in the tissue plays a crucial role in inhibiting inflammation. If the receptor is activated, the cell releases fewer pro-inflammatory signal substances, or cytokines. The scientists have now discovered that the substance beta-carophyllene, which composes between 12 and 35 percent of the cannabis plant’s essential oil, activates the CB2 receptor selectively.”

http://www.sciencedaily.com/releases/2008/07/080720222549.htm

Marijuana Has Anti-Inflammatory That Won’t Get You High

“Marijuana supporters have long argued that the plant’s active ingredients, known as cannabinoids, are safe and effective treatments for pain, nausea, and other ailments.

The most active cannabinoid—delta-9-tetrahydrocannabinol, or THC—is known to have anti-inflammatory properties. But it is also responsible for the plant’s psychotropic effects.

Now researchers say that another cannabinoid, called beta-caryophyllene, or (E)-BCP, helps combat inflammation without affecting the brain.

(E)-BCP is already part of many people’s daily diets, the researchers note. Foods that are particularly high in the compound include black pepper, oregano, basil, lime, cinnamon, carrots, and celery.

Essential oils from cannabis plants—whose leaves and flowers are used to make the marijuana drug—contain up to 35 percent (E)-BCP.”

http://news.nationalgeographic.com/news/2008/06/080624-marijuana.html

The role of cannabinoid system on immune modulation: therapeutic implications on CNS inflammation.

Abstract

“There is a growing amount of evidence suggesting that cannabinoids may be neuroprotective in CNS inflammatory conditions. Advances in the understanding of the physiology and pharmacology of the cannabinoid system have increased the interest of cannabinoids as potential therapeutic targets. Cannabinoid receptors and their endogenous ligands, the endocannabinoids, have been detected in cells of the immune system, as well as in brain glial cells. In the present review it is summarized the effects of cannabinoids on immune reactivity and on the regulation of neuroinflammatory processes associated with brain disorders with special attention to chronic inflammatory demyelinating diseases such as multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pubmed/16026313