Cannabinoids: potential anticancer agents.

Abstract

“Cannabinoids – the active components of Cannabis sativa and their derivatives – exert palliative effects in cancer patients by preventing nausea, vomiting and pain and by stimulating appetite. In addition, these compounds have been shown to inhibit the growth of tumour cells in culture and animal models by modulating key cell-signalling pathways. Cannabinoids are usually well tolerated, and do not produce the generalized toxic effects of conventional chemotherapies. So, could cannabinoids be used to develop new anticancer therapies?”

http://www.ncbi.nlm.nih.gov/pubmed/14570037

 

Search: Study says marijuana fights cancer

“Researchers in Madrid say the main psychoactive ingredient in marijuana (what is it?) and other “cannabinoids” (what are those?) could help slow cancer growth, as well as manage many cancer symptoms (like what?).  Scientists studied cancer cells (which type?) that grow faster than normal cells, and discovered that the cancer cells died whenever they were exposed to the pot ingredient.”

http://specials.msn.com/a-list/healthyliving/marijuana-fights-cancer-popular-pages

Marijuana compound could help fight breast cancer – ABC News

“There may be a new weapon in the fight against aggressive forms of breast cancer in the future, and it comes from an unlikely source: Marijuana. Researchers at California Pacific Medical Center in San Francisco believe a compound in marijuana may help.

The research funded by the California Breast Cancer Research Program builds on more than a decade of studies involving the genes responsible for the spread of cancer. Now scientists have found at the cellular level, a compound in cannabis inhibits the gene that controls the spread of cancer.

“The problem is not the cancer itself, the problem is the spread of the cancer,” said cancer researcher Yvez Desprez, Ph.D.

Cancer researcher Pierre Desprez points to the gene ID-1 as the trigger.

“When this type of gene is expressed, the cells basically go crazy and they’re very aggressive and they metastasize everywhere in the body,” said Desprez.

“We could expect that if we create really effective inhibitors against it, we could potentially treat many types of aggressive cancers,” said cancer researcher Sean McAllister, Ph.D.

Their research in breast cancer cell lines focused on using a non-toxic compound in cannabis to target the ID-1 gene.

“What we found was cannabidiol is a particularly good inhibitor of this gene that’s responsible for the ability of cancer cells to become very aggressive,” said McAllister.”

http://abclocal.go.com/kgo/story?section=news/health&id=5771385

Scientists believe marijuana compound could fight cancer

“Scientists in California believe they may have discovered a compound in marijuana that can reduce the aggressiveness of some forms of cancer.

The San Francisco Gate reports on the data that has been years in the making. While marijuana has been shown to help reduce nausea and pain in cancer patients, scientists believe that a compound in marijuana has the ability to “turn off” the activity of a gene responsible for metastasis in breast and other types of cancers.

The research team is working out of San Francisco’s California Pacific Medical Center Research Institute and have been working for years on the study. The compound they’re focused on, called cannabidiol, does not produce the psychotropic high associated with marijuana.

Last year, the team published a small study showing the positive effects of cannabidiol on mice. New data is about to be released that expands upon the previous results that the researchers hope will help propel the study even further.

“The preclinical trial data is very strong, and there’s no toxicity. There’s really a lot of research to move ahead with and to get people excited,” said Sean McAllister, who is working alongside scientist Pierre Desprez in the study.

Desprez and McAllister believe that their merging of separate areas of study was serendipitous.

Desprez had been studying the protein ID-1, which he found to play an important role in how cancer could spread. McAllister, on the other hand, was focused on studying anabolic steroids in drug abuse. He soon became focused on with the role non-psychotropic cannabidiol, or CBD, interacts with cancer.

McAllister, after hearing an internal seminar from Desprez on his studies of ID-1, came up with the question “How effective would cannabidiol be on targeting metastatic cancer cells?”

The two then teamed up, with Desprez armed with ID-1 cancer-causing protein, and McAllister with CBD, his cancer-fighting compound.

For their experimentation, the doctors exposed ID-1 to CBD in a petri dish. In a shocking result, the ID-1, the cancer-causing protein, reverted to a normal state and stopped acting “crazy.”

“We thought we did the experiment the wrong way,” McAllister said of the overwhelming results.

However, their results proved to be consisted.

“I told Sean, ‘Maybe your drug is working through my gene,’ ” Desprez said.

What the researchers have discovered thus far in their research is that CBD turns off the overexpression of ID-1, which prevents it from traveling to foreign tissues. Thus, the metastasization – cancer’s fatal ability – is blocked.

In the wake of their positive results, the doctors were forced to emphasize that the CBD will only work in the presence of high levels of ID-1 and these do not include all cancerous tumors but, rather, aggressive, metastatic cells. High levels have been found in leukemia, colorectal, pancreatic, lung, ovarian, brain and other cancers.”
Read more: http://www.irishcentral.com/news/Scientists-believe-marijuana-compound-could-fight-cancer-170689736.html#ixzz29rQbc2oS

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