Latest Science: Non-Psychotropic Cannabinoid Inhibits Colon Cancer Cell Proliferation

The administration of the non-psychotropic cannabis plant constituent cannabidiol (CBD) is protective in an experimental model of colon cancer, according to preclinical trial data published online in the Journal of Molecular Medicine.

Investigators at the University of Naples assessed the effect of CBD on colon carcinogenesis in mice. Researchers reported that CBD administration was associated with cancerous tumor reduction and reduced cell proliferation.

Authors wrote: “Although cannabidiol has been shown to kill glioma cells, to inhibit cancer cell invasion and to reduce the growth of breast carcinoma and lung metastases in rodents, its effect on colon carcinogenesis has not been evaluated to date. This is an important omission, since colon cancer affects millions of individuals in Western countries. In the present study, we have shown that cannabidiol exerts (1) protective effects in an experimental model of colon cancer and (2) antiproliferative actions in colorectal carcinoma cells.”

Authors also acknowledged that CBD possesses “an extremely safe profile in humans.” They concluded, “[O]ur findings suggest that cannabidiol might be worthy of clinical consideration in colon cancer prevention.”

Clinical review data published in the scientific journal Current Drug Safety in December concluded that CBD is “non-toxic” to healthy cells and is “well tolerated” in humans. Nevertheless, cannabidiol is presently classified under federal law as a schedule I prohibited substance. Such substances are required by law to possess “a high potential for abuse,” “a lack of accepted safety … under medical supervision,” and “no currently accepted medical use in treatment in the United States.”

Separate preclinical trials evaluating the anti-cancer activities of cannabinoids and endocannabinoids show that their administration can inhibit the proliferation of a variety of cancerous cell lines, including breast carcinoma, prostate carcinoma, gastric adenocarcinoma, skin carcinoma, leukemia cells, neuroblastoma, lung carcinoma, uterus carcinoma, thyroid epithelioma, pancreatic adenocarcinoma, cervical carcinoma, oral cancer, biliary tract cancer (cholangiocarcinoma), and lymphoma. NORML provides summaries and links to these studies here.

Full text of this latest study, “Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer,” appears in the Journal of Molecular Medicine.

Cannabinoid Administration Delays Huntington’s Disease Progression In Animals — Time To Initiate Human Trials

The combined administration of the plant cannabinoids THC and CBD (cannabidiol) provide neuroprotection in rat models of Huntington’s Disease (HD), according to experimental data to be published in the Journal of Neuroscience Research.

Huntington’s Disease is an inherited degenerative brain disorder characterized by motor abnormalities and dementia produced by selective lesions in the cerebral cortex and, in particular, the striatum. There are presently no known conventional therapies available to alleviate HD symptoms or delay HD-associated striatal degeneration.

An international team of investigators from Spain, Italy, and the United Kingdom assessed whether THC and CBD-rich botanical extracts could delay the progress of the disease in laboratory animals. Authors reported, “[O]ur data demonstrate that a [one to one] combination of THC and CBD-enriched botanical extracts protected striatal neurons against … toxicity.” By contrast, the administration of individual, selective synthetic cannabinoid agonists did not produce similarly favorable outcomes.

Investigators concluded, “In our opinion, these data provide sufficient preclinical evidence to justify a clinical evaluation of [one to one THC to CBD] cannabis-based medicine … as a neuroprotective agent capable of delaying disease progression in patients affected by HD, a disorder that is currently poorly man- aged in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies.”

Additional studies documenting the disease modifying potential of marijuana is available in the NORML handbook, Emerging Clinical Applications For Cannabis & Cannabinoids: Fourth Edition, available online here.

Additional information on this study will appear in this week’s NORML news update. To receive these e-mail updates free, please sign up here.

Project CBD: Will The Industry Support The Movement?

By Fred Gardner

Project CBD has just sent out its introductory pitch to California dispensaries. ProjectCBD.org is the medical marijuana movement living up to its name,” explains outreach coordinator Sarah Russo, optimistically, as she asks the dispensaries to participate in a “collective research effort.” But what are the chances that the dispensary owners, intent on building their own brands, will support a venture aimed at advancing the movement as a whole?

CBD, in case you’re just joining us, is Cannabidiol —a component of the Cannabis plant known to have anti-inflammatory, anti-tumor and other beneficial medical effects. CBD is not psychoactive and actually counters the psychoactive effects of THC. It is the predominant cannabinoid in hemp —plants grown to produce fiber or growing wild. CBD levels go down and THC levels go up when plants are bred to maximize psychoactive effect, as they have been in the U.S. for many generations of plants and people.

It was widely assumed for a long time that CBD had been almost entirely bred out of the Cannabis being grown in California for medical/commercial purposes. And because no analytic chemistry labs were testing Cannabis samples before the winter of 2008-09, there was no way to assess cannabinoid content. Overseas things were different. For many years researchers have been exploring the medical potential of CBD, and G.W. Pharmaceuticals conducted successful clinical trials and got U.K. government approval to market Sativex, a whole-plant extract with equal amounts of CBD and THC, for use by MS patients. Canada and Spain have also issued approvals for Sativex.

The situation in California changed in 2008 when Steve DeAngelo arranged for a lab to test the Cannabis he was providing at Oakland’s Harborside Health Center. DeAngelo had to fund a start-up to accomplish this. When Harborside opened in 2006 he had phoned every analytic lab in the Bay Area and been turned down when he mentioned the C word. In the spring of ’08 he decided to back two entrepreneurs who were launching a lab —the aptly named “Steep Hill”— and to supply them with a large, steady stream of samples to test for mold and cannabinoid content (THC, CBD and CBN, a breakdown product indicative of freshness). At least eight more labs have started testing Cannabis in California since then, and there are labs in Montana and Colorado. ProjectCBD’s Russo says, “We seem to hear from a new lab every week.”

It turns out that CBD is not all that rare —about one in every 600 samples tested by the labs is found to be high in CBD. Evidently, that’s the rate at which a mutation occurs resulting in an excess of the enzyme that transforms a precursor molecule of CBD and THC into one or the other. More than 25 CBD-rich strains have been identified, and Russo says, “We seem to hear about a new strain every week, too”

The prospect of CBD-rich cannabis becoming available prompted the Society of Cannabis Clinicians to plan a data collection effort. Jeffrey Hergenrather, MD, President of the SCC, had spent years listening to talks about CBD at meetings of the International Cannabinoid Research Society, wishing he could observe its effects on real patients. Hergenrather and co-worker Stacey Kerr, MD have now drafted a survey aimed at documenting patients’ answers to some basic questions about the effects of CBD-rich Cannabis. (For purposes of data collection, “CBD-rich” has been defined as 4% or more CBD, regardless of THC content. The amount of CBD that a given strain contains isn’t the only factor influencing the effects it will exert when ingested. The ratio of CBD to THC may be as or more important. Terpenoid and flavonoid content also appear to be very important.)

Project CBD was launched to publicize and promote the SCC survey(s). Martin A. Lee, the author of Acid Dreams, had been writing about CBD for O’Shaughnessy’s and convinced your correspondent that its re(introduction) into the grassroots supply was going to be a huge, ongoing story and would warrant its own journal of sorts. Over the past year we put a lot of effort into encouraging production by plant breeders and growers who had strains testing high in CBD. Many dispensary owners have been reluctant to stock CBD-rich strains because their present customers are seeking —or are not adverse to— Cannabis that causes euphoria or sedation. In other words, THC content sells, it’s a sure thing. Why should a dispensary spend money and devote shelf space to a type of Cannabis that most medical users haven’t heard of and whose effects are unproven?

Growers, in turn, have to anticipate the wants of dispensary buyers, and are reluctant to devote valuable garden space to plants for which there is no established market. ?Demand at the dispensary level might not take off until effectiveness is established. Which might not happen until significant numbers of patients have tried CBD-rich Cannabis and taken the SCC survey to report their results. Or, as Martin says, “there could be a tsunami of interest any day now.”

ProjectCBD.org provides the whole story to date and a “CBDiary” noting recent developments. The big news as of March 1: for the first time, a California grower has “stabilized” a CBD-rich strain. Lawrence Ringo of the Southern Humboldt Seed Collective is now offering seeds of “Sour Tsunami” that have a one-in-four chance of containing 10-11% CBD (and 6-7% THC).

Read all about it here.

Fred Gardner is the managing editor of O’Shaughnessy’s, the journal of cannabis in clinical practice. His email is fred@plebesite.com.

NORML’s updated primer on existing and potential cannabinoid and cannabis therapies is found here.

Cannabis Once Again Shown To Halt Cancer Growth — So Why Aren’t We Studying It In Humans?

[Editor's note: This post is excerpted from this week's forthcoming NORML weekly media advisory. To have NORML's media advisories delivered straight to your in-box, sign up for NORML's free e-zine here.]

The administration of THC reduces the tumor growth of metastatic breast cancer and “might constitute a new therapeutic tool for the treatment” of cancerous tumors, according to preclinical data published online in the journal Molecular Cancer.

Investigators from Complutense University in Madrid assessed the anti-tumor potential of THC and JWH-133, a non-psychotropic CB2 receptor-selective agonist, in the treatment of ErbB2-positive breast tumors – a highly aggressive form of breast cancer that is typically unresponsive to standard therapies.

Researchers reported, “[B]oth Delta-9-tetrahydrocannabinol … and JWH-133 …reduce tumor growth [and] tumor number [in mice]. … [T]hese results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.”

In 2007, investigators at the California Pacific Medical Center Research Institute reported that the administration of the nonpsychoactive cannabinoid CBD limited breast cancer metastasis in a manner that was superior to comparable synthesized agents.

Previous preclinical studies assessing the anticancer properties of cannabinoids have shown that they inhibit the proliferation of a wide range of cancers, including brain cancer, prostate cancer, oral cancers, lung cancer, skin cancer, pancreatic cancer, biliary tract cancers, and lymphoma.

Full text of the study, “Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition,” is available online here.

A Couple Of Recent Studies The Mainstream Media Forgot To Mention

Investigators and pundits alike are fond of calling for ‘more research’ into the safety and efficacy of marijuana and its active compounds. Ironically, when such calls are heeded and new research is published, nobody wants to talk about it.

For example, researchers at the State University of New York (SUNY), Upstate Medical University in Syracuse published data in the June issue of the journal Pharmacology concluding that the administration of the plant cannabinoids delta-8-THC and delta-9-THC halted cellular respiration and tumor growth in human oral cancer cells. Specifically, investigators reported that cannabinoids were a “potent inhibitor” of Tu183 human cancer cells, a notoriously difficult to treat type of oral cancer.

Of course, this is hardly the first time that pot’s compounds have been demonstrated to possess anti-cancer properties. As has been widely reported here and elsewhere, US government researchers were first aware of this finding over 35 years ago, and today there exist published scientific studies demonstrating that cannabinoids can inhibit the proliferation of a wide range of cancers — including brain cancer, prostate cancer, breast cancer, lung cancer, skin cancer, pancreatic cancer, biliary tract cancer, and lymphoma. Nonetheless, abstract prohibitionist concerns regarding marijuana’s supposed cancer risk continue to dominate the headlines while actual scientific studies debunking these allegations tend to go unnoticed.

Similarly, preclinical data published online last week in the journal Cell Communication and Signaling reported that the administration of the non-psychoactive cannabinoid cannabidiol (CBD) increases adult neurogenesis (the active production of new neurons) in laboratory animals. Authors speculated that cannabis’ pro-neurogenic effects may explain why the plant appears to be useful in the treatment of certain neurodegenerative disorders like Alzheimer’s disease or ALS.

As I wrote last week, to date there are now over 20,000 published studies or reviews in the scientific literature pertaining to marijuana and its active compounds — making marijuana the most studied plant on Earth. But what’s the point in further research if nobody even bothers to pay attention to the research that’s already been done?