Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.

Abstract

“Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. Thus, we investigated its possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice. AOM treatment was associated with aberrant crypt foci (ACF, preneoplastic lesions), polyps, and tumour formation, up-regulation of phospho-Akt, iNOS and COX-2 and down-regulation of caspase-3. Cannabidiol-reduced ACF, polyps and tumours and counteracted AOM-induced phospho-Akt and caspase-3 changes. In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB(1)-, TRPV1- and PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.”

http://www.ncbi.nlm.nih.gov/pubmed/22231745

Dixie X Hemp CBD Wellness Products Online Store Now Open!

“At long last, Dixie X the revolutionary hemp CBD powered wellness products from Dixie Elixirs & Edibles are now available for sale over the Internet at dixiex.com.

Medical Marijuana Inc. (OTC: MJNA), a leading hemp industry innovator, is pleased to announce a new on-line sales website for its Hemp-based Dixie X line of products:  www.dixiex.comThis announcement supports the company’s large scale national launch of on-line sales of its Hemp-based Cannabidiol (CBD) enriched health and wellness Dixie X products.

According to the company, since Dixie X is manufactured from non-THC high CBD concentrate industrial Hemp it can be legally shipped to consumers in all 50 states in the U.S. as well as internationally.”

http://dixieelixirs.com/dixie-x-store-open/

Cancer-fighting Potential of Cannabidiol Bodes Well for Dixie X Hemp Products

“Research by California Pacific Medical Center indicating that cannabidiol (CBD), a non-psychotropic compound found in hemp, may arrest the spread of aggressive, metastatic cancer cells, is drawing the attention of the medical community. John Malanca of medical cannabis resource UnitedPatientsGroup.com believes this encouraging news will also bring CBD to the attention of health-minded consumers.

“Many people want the health benefits of CBD, but they don’t want to get ‘high,’” said Malanca. “Dixie X products deliver a new option, and as our understanding and awareness of the health benefits of CBD grow, so does the attractiveness of Dixie X CBD wellness products.”

http://www.prweb.com/releases/cbd-pills/medical-cannabis-resource/prweb9985704.htm

Can Cannabidiol (CBD) Fight Metastatic Cancer? According to the latest research the answer is yes.

“Medical Marijuana Inc. (OTC: MJNA), a leading hemp industry innovator, is pleased to report on a September 18 San Francisco Chronicle Article, “Pot compound seen as tool against cancer.”

The article states that scientists at California Pacific Medical Center who have been researching marijuana’s compounds for the 20 years have found that Cannabidiol, or CBD, has the ability to “turn off” the DNA that causes “breast and other types of cancers” to metastasize. CBD is the second-most abundant cannabinoid within marijuana, but does not cause the psychotropic high of THC.

As stated in the article: “We started by researching breast cancer,” said scientist Pierre Desprez. “But now we’ve found that Cannabidiol works with many kinds of aggressive cancers–brain, prostate–any kind in which these high levels of ID-1 are present.”

According to the Chronicle article, when scientists first exposed metastatic cancer cells to Cannabidiol in a petri dish, “the cells not only stopped acting crazy but they also started to revert to a normal state. Both scientists were shocked…But they got the same results each time they did it.”

“This article and the findings it reports just confirm what many have known, that Cannabidiol or CBD have tremendous health and wellness potential. We are pleased that our Dixie X line of products are available right now to patients who have an immediate need for CBD and are searching for an easy way to find it,” states Ted Caligiuri, Interim President of MJNA. “We take great pride in knowing that our Dixie X line may be of significant health benefit to not only all cancer patients, but those in late stages of metastatic disease. We are also looking forward to the clinical trials that will soon be underway and thank the National Institute of Health, Susan G. Komen Foundation and others for their unwavering commitment to funding this necessary research.”

https://www.prnewswire.com/news-releases/can-cannabidiol-cbd-fight-metastatic-cancer-according-to-the-latest-research-the-answer-is-yes-170681736.html

Pot compound seen as tool against cancer

“Marijuana, already shown to reduce pain and nausea in cancer patients, may be promising as a cancer-fighting agent against some of the most aggressive forms of the disease.

A growing body of early research shows a compound found in marijuana – one that does not produce the plant’s psychotropic high – seems to have the ability to “turn off” the activity of a gene responsible for metastasis in breast and other types of cancers.

Two scientists at San Francisco’s California Pacific Medical Center Research Institute first released data five years ago that showed how this compound – called cannabidiol – reduced the aggressiveness of human breast cancer cells in the lab.”

Marijuana’s better known cannabinoid – delta-9 tetrahydrocannabinol, or THC – had already shown some anticancer properties in tumors, but the non-psychotropic cannabidiol had largely gone unstudied. McAllister initial research showed CBD had anticancer potential as well.”

http://www.sfgate.com/health/article/Pot-compound-seen-as-tool-against-cancer-3875562.php

Marijuana compound could stop aggressive cancer metastasis

“A compound found in cannabis could halt the spread of many forms of aggressive cancer, scientists have claimed.

Researchers found that the compound, called cannabidiol, had the ability to “switch off” the gene responsible for metastasis in an aggressive form of breast cancer, the Daily Mail reported.

Importantly, this substance does not produce the psychoactive properties of the cannabis plant.

The team from the California Pacific Medical Center, in San Francisco, first spotted its potential five years ago, after it stopped the proliferation of human breast cancer cells in the lab, the report said.

They discovered that the compound had turned off the overexpression of ID-1, stopping them from travelling to distant tissues.

Other potentially treatable cancers are forms of leukaemia, lung, ovarian and brain cancers, which also have high levels of ID-1.”

http://in.news.yahoo.com/marijuana-compound-could-stop-aggressive-cancer-metastasis-064950912.html

Endocannabinoids in endocrine and related tumours.

“The ‘endocannabinoid system’, comprising the cannabinoid CB1 and CB2 receptors, their endogenous ligands, endocannabinoids and the enzymes that regulate their biosynthesis and degradation, has drawn a great deal of scientist attention during the last two decades. The endocannabinoid system is involved in a broad range of functions and in a growing number of physiopathological conditions. Indeed, recent evidence indicates that endocannabinoids influence the intracellular events controlling the proliferation of numerous types of endocrine and related cancer cells, thereby leading to both in vitro and in vivo antitumour effects. In particular, they are able to inhibit cell growth, invasion and metastasis of thyroid, breast and prostate tumours. The chief events of endocannabinoids in cancer cell proliferation are reported highlighting the correspondent signalling involved in tumour processes: regulation of adenylyl cyclase, cyclic AMP-protein kinase-A pathway and MEK-extracellular signal-regulated kinase signalling cascade.

Up to date since the isolation and characterisation of the psychoactive component of Cannabis sativa, Δ9-tetrahydrocannabinol (Δ9-THC), about 60 different plant terpeno-phenols more or less related to THC have been isolated and defined cannabinoids. They include cannabidiol (CBD), cannabinol, cannabigerol and cannabichromene. The discovery of these principles stimulated the generation of a whole range of synthetic analogues that included not only compounds structurally similar to phytocannabinoids, but also analogues with different chemical structures, including classic and non-classic cannabinoids and aminoalkylindoles (Howlett et al. 2002) as well as the subsequently discovered endogenous arachidonic acid derivatives or endocannabinoids. The discovery of this family of endogenous cannabinoids (Devane et al. 1992, Mechoulam et al. 1995, Sugiura et al. 1995) has focused much attention on cannabinoids and their pharmacological properties during the last few years (Di Marzo et al. 2004).”

http://erc.endocrinology-journals.org/content/15/2/391.long

CANNABIDIOL AS POTENTIAL ANTICANCER DRUG.

“Over the past years, several lines of evidence support an antitumorigenic effect of cannabinoids including Δ(9) -tetrahydrocannabinol (Δ(9) -THC), synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of Δ(9) -THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for Δ(9) -THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents.”

http://www.ncbi.nlm.nih.gov/pubmed/22506672

Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma

“Delta(9)-Tetrahydrocannabinol (THC) exhibits antitumor effects on various cancer cell types, but its use in chemotherapy is limited by its psychotropic activity. We investigated the antitumor activities of other plant cannabinoids, i.e., cannabidiol, cannabigerol, cannabichromene, cannabidiol acid and THC acid, and assessed whether there is any advantage in using Cannabis extracts (enriched in either cannabidiol or THC) over pure cannabinoids. Results obtained in a panel of tumor cell lines clearly indicate that, of the five natural compounds tested, cannabidiol is the most potent inhibitor of cancer cell growth (IC(50) between 6.0 and 10.6 microM), with significantly lower potency in noncancer cells. The cannabidiol-rich extract was equipotent to cannabidiol, whereas cannabigerol and cannabichromene followed in the rank of potency. Both cannabidiol and the cannabidiol-rich extract inhibited the growth of xenograft tumors obtained by s.c. injection into athymic mice of human MDA-MB-231 breast carcinoma or rat v-K-ras-transformed thyroid epithelial cells and reduced lung metastases deriving from intrapaw injection of MDA-MB-231 cells. Judging from several experiments on its possible cellular and molecular mechanisms of action, we propose that cannabidiol lacks a unique mode of action in the cell lines investigated. At least for MDA-MB-231 cells, however, our experiments indicate that cannabidiol effect is due to its capability of inducing apoptosis via: direct or indirect activation of cannabinoid CB(2) and vanilloid transient receptor potential vanilloid type-1 receptors and cannabinoid/vanilloid receptor-independent elevation of intracellular Ca(2+) and reactive oxygen species. Our data support the further testing of cannabidiol and cannabidiol-rich extracts for the potential treatment of cancer.”

In conclusion, our data indicate that cannabidiol, and possibly Cannabis extracts enriched in this natural cannabinoid, represent a promising nonpsychoactive antineoplastic strategy. In particular, for a highly malignant human breast carcinoma cell line, we have shown here that cannabidiol and a cannabidiol-rich extract counteract cell growth both in vivo and in vitro as well as tumor metastasis in vivo. Cannabidiol exerts its effects on these cells through a combination of mechanisms that include either direct or indirect activation of CB2 and TRPV1 receptors and induction of oxidative stress, all contributing to induce apoptosis. Additional investigations are required to understand the mechanism of the growth-inhibitory action of cannabidiol in the other cancer cell lines studied here.”

http://jpet.aspetjournals.org/content/318/3/1375.long

Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells

“Invasion and metastasis of aggressive breast cancer cells is the final and fatal step during cancer progression, and is the least understood genetically. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Clearly, effective and nontoxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. Using a mouse model, we previously determined that metastatic breast cancer cells became significantly less invasive in vitro and less metastatic in vivo when Id-1 was down-regulated by stable transduction with antisense Id-1. It is not possible at this point, however, to use antisense technology to reduce Id-1 expression in patients with metastatic breast cancer. Here, we report that cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness.

Cannabinoids Reduce the Growth of Aggressive Human Breast Cancer Cells”

Cannabinoids Reduce Breast Cancer Cell Invasiveness

CBD Down-regulates Id-1 Expression

The Effects of CBD on Invasion and Id-1 Protein Expression Can Be Reproduced in an Additional Breast Cancer Cell Line

Plant cannabinoids are stable compounds with low-toxicity profiles that are well tolerated by animals and humans during chronic administration. 

If CBD shows efficacy for treatment of metastatic breast cancer in humans, the low toxicity of the compound would make it an ideal candidate for chronic administration.”

http://mct.aacrjournals.org/content/6/11/2921.long