In his 1971 State of the Union speech, President Richard Nixon declared war on cancer, prompting passage of the National Cancer Act, aimed at making the "conquest of cancer a national crusade." Just four years later, scientists from the National Cancer Institute published a study demonstrating that a group of compounds taken from a common, widely cultivated plant shrank lung tumors that had been implanted in mice, extending their survival.
In a world that made sense, this plant and the anticancer drugs it produced would have been rushed into further testing, and we'd have known in a few years whether they had potential as treatments for human cancers. Instead, research proceeded at a glacial pace, with almost no further progress till the 1990s. Since then, vast quantities of lab and animal data have confirmed those early findings, but studies of these plant compounds in actual human beings with cancer remain nearly nonexistent.
What got in the way was Nixon's other war, the "war on drugs." The plant in question was cannabis sativa -- marijuana -- public enemy number one in that other war, and discovering that marijuana had beneficial properties was the last thing the U.S. government wanted to do.
Dr. Manuel Guzman of Complutense University in Madrid, lead author of the only human study yet published of a cannabinoid as cancer treatment, puts it slightly more diplomatically. The lack of immediate followup to those early reports "remains a mystery to me," he says. Guzman cites a number of obstacles to humantrials, including the fact that cannabinoids are "still seen by many doctors and regulatory agencies as drugs of abuse," as well as "lots of paperwork" and a lack of commercial interest in natural compounds that can't be patented.
Complicating things further, the relative vacuum created by the lack of human studies and the hostility of the U.S. government to the whole question of marijuana's beneficial effects has left the field wide open for zealots who promote cannabis as a "cure" for cancer as if it were already a proven fact rather than a possibility in desperate need of serious study.
A Protective Effect?
Instead of researching cannabinoids as anticancer drugs, federal officials have continued to falsely imply that marijuana causes lung cancer. For example, a 2002 brochure for parents, "Talk to Your Child About Marijuana," still available on the Office of National Drug Control Policy Web site, advises, "Smoking marijuana is as least as bad as smoking cigarettes."
In fact, the largest, most well-controlled studies have consistently failed to find an increased risk of lung cancer or other typically tobacco-related cancers among marijuana smokers. These include a 65,000-patient 1997 study conducted at Kaiser Permanente in Oakland, California and a 2006 case-control study (in which patients with cancer were matched with similar patients without cancer to compare risk factors) from the UCLA lab of Dr. Donald Tashkin, one of the world's leading experts on the pulmonary effects of drugs.
In the UCLA study, there was a consistent trend -- albeit short of statistical significance -- toward lower cancer risk among even the heaviest marijuana smokers. This was a surprise to some, given that marijuana smoke contains many of the same carcinogenic compounds as tobacco smoke. The researchers wrote:
Although purely speculative, it is possible that such inverse associations may reflect a protective effect of marijuana. There is recent evidence from cell culture systems and animal models that 9-tetrahydrocannabinol, the principal psychoactive ingredient in marijuana, and other cannabinoids may inhibit the growth of some tumors by modulating key signaling pathways leading to growth arrest and cell death, as well as by inhibiting tumor angiogenesis. These antitumoral associations have been observed for several types of malignancies including brain, prostate, thyroid, lung, and breast.
In an October 2003 review in the journal Nature Reviews: Cancer, Guzman detailed the extensive body of test-tube and animal research showing that cannabinoids inhibit tumors of the lung, uterus, skin, breast, prostate and brain (including gliomas, the type of tumor that killed Sen. Edward Kennedy). He also noted: "Cannabinoids have favorable drug-safety profiles and do not produce the generalized toxic effects of conventional chemotherapies. Cannabinoids are selective antitumor compounds, as they can kill tumor cells without affecting their non-transformed counterparts."
Such selectivity is exactly what you want in an anticancer drug. The reason chemotherapy can be so awful is that most chemo drugs aren't selective enough; they kill cancer cells, but are also toxic to healthy cells, leading to vomiting, hair loss and other miseries.
The 'Cure'?
Nearly all of the evidence about cannabinoids as anticancer drugs comes from lab studies using cell cultures or animals with experimentally implanted tumors. The annals of medical research are littered with drugs that looked promising in the lab but didn't work in people. Still, that doesn't stop some enthusiasts from touting cannabis as a cure for cancer, sometimes making even open-minded scientists and medical marijuana advocates nervous.
When I worked at the Marijuana Policy Project, we received several impassioned emails imploring us to tell Sen. Kennedy that cannabis could cure his brain tumor. Others touted Canadian Rick Simpson's "Healing Hemp Oil" Web site, Phoenix Tears.
In a series of videos, letters and other materials on the site, Simpson -- who has had repeated run-ins with law enforcement over his cannabis-related activities and was, according to a Dec. 14 posting, staying in Europe indefinitely to avoid arrest -- promotes what he calls "hemp oil" as a "simple herbal cure for cancer. I have used these extracts to cure three areas of skin cancer on my own body, also, I have cured cancers for others." Simpson also touts hemp oil for pain and a variety of other conditions.
The site includes video and written instructions for making the preparation. The procedure involves using a solvent such as naphtha or isopropyl alcohol to extract the THC from marijuana, then boiling off the solvent using a rice cooker to leave a thick oil with a high THC concentration.
Simpson warns readers away from conventional cancer treatments: "Hemp oil has a very high success rate in the treatment of cancer, unfortunately many people who come to me have been badly damaged by the medical system with their chemo and radiation etc. The damage such treatments cause have a lasting effect and people who have suffered the effects of such treatments are the hardest to cure."
He offers numerous stories and testimonials describing seemingly hopeless cancers cured by hemp oil, but no controlled, scientific experiments.
And critics find plenty to worry about. First, they note, despite warnings and disclaimers on the site, the procedure for making the medicine is risky. Mitch Earleywine, author of Understanding Marijuana and a professor of psychology at the State University of New York at Albany, calls the do-it-yourself procedure "outrageously dangerous. Even if you don't light yourself on fire, you may end up with leftover solvent that would slowly poison the healthiest of us."
There's a reason scientists don't base conclusions on anecdotes, Earleywine explains. "Cancer remits spontaneously sometimes, which is a good thing. Unfortunately, it leads to superstitious conditioning so people think that whatever they did last must be the source of the cure. Especially with some cancers, where a great many people die, all the spontaneous recoveries associated with hemp oil get remembered while all those that don't either get forgotten or attributed to the horrors of the disease."
Earleywine stresses that he is not dismissing the possibility that some form of cannabis might be an effective cancer treatment. "THC killing tumors is actually true," he says, "but we're not at the human stage [of research]."
Simpson is dismissive of critics who cite the lack of human studies. "How are you going to do controlled studies when it is illegal in Canada to do so?" he said in an emailed response to questions.
In fact, researcher Mark Ware of McGill University in Montreal has done clinical trials of medical cannabis in Canada, including a study comparing several different cannabis preparations in use by chronic pain patients.
Simpson calls the idea of spontaneous cancer remissions "nonsense." As for possible risks of his preparation, he argues, "It is irresponsible to give people liver toxic chemicals, chemotherapy and radiation, so if they are talking about irresponsible why do not look at their own medical system? It is not irresponsible to save peoples lives with a harmless natural, non-addictive medicine from nature. If you watch our documentary, you will see that I use a simple water purification process to get rid of solvent residue. I have been ingesting oil for over eight years and I have supplied this oil to thousands of people who also have experienced no problems with solvent residue."
While cautious about reports that are "solely anecdotal," Paul Armentano, deputy director and resident science wonk at the National Organization for the Reform of Marijuana Laws, lays blame for the lack of proper data at the foot of prohibition. "It is a shame that lone individuals must try and engage in the work that the medical establishment should be undertaking, yet have turned a blind eye to," he says. "Unfortunately, what we have is speculation rather than hard science, and we only have the politicization of cannabis to blame."
The Long and Winding Research Road
The one human study of a cannabinoid cancer treatment published thus far was conducted by Dr. Guzman and colleagues and published online in June 2006 by the British Journal of Cancer. The scientists infused a THC solution directly into the tumors of nine patients with glioblastoma multiforme, a deadly form of brain cancer, for whom standard treatments had failed. This small pilot study wasn't aimed at proving that THC worked, simply that it was safe to administer to these otherwise doomed patients .
It proved entirely safe, with no negative effects attributed to the THC and no "overt psychoactive effects." And while there were no miracle cures, there were glimmers of possible efficacy. In one patient with an "extremely aggressive" cancer, tumor growth was curbed for nine weeks. In another, symptoms improved, although tumor growth was not stopped. And in some cases, lab tests with cells taken from tumor biopsies showed that THC decreased the number of viable cancer cells.
Guzman and colleagues noted that THC may not be the best cannabinoid to use as a cancer treatment, as others have been shown more potent in lab tests. And while the direct infusion technique delivered a high THC concentration to specific locations, it may not have reached all parts of these large tumors.
Still, the results were positive enough that the researchers urged further tests, including studies of cannabinoids in combination with other cancer drugs. Guzman is hoping to do more studies, but notes that with all the bureaucratic, procedural and financial hurdles, "The way ahead is long and winding."
But if more human studies aren't happening yet, lab work continues to produce intriguing results. Just this month, the journal Molecular Cancer Therapeutics published a new study providing the first evidence that combination cannabinoid therapy is more potent than using THC or other cannabinoids as single agents.
Sean McAllister and colleagues from the California Pacific Medical Center Research Institute in San Francisco tested THC, cannabidiol (CBD) and both drugs combined on human glioblastoma cell lines. In two of the three cell lines tested, the THC/CBD combination proved the most potent -- more so than would be expected by just adding the anticancer effects of the two drugs together, suggesting a synergistic action.
"Combinations, compared to individual drug treatments with specific cannabinoid-based compounds, may represent an improvement for the treatment of patients with glioblastoma and perhaps additional cancers," McAllister says. "It is also possible that other constituents of Cannabis sativa which are not structurally related to cannabinoids could improve antitumor activity when combined."
That leads to an obvious question: Why not use the whole plant -- whether smoked, vaporized, or in some sort of extract like Simpson's? "In regard to brain cancer, it is highly unlikely that effective concentrations of either Δ9-THC or CBD could be reached by smoking cannabis," McAllister says. "In regard to additional cancers, I feel defined formulations and dosing will be needed in order to effectively treat patients."
McAllister says his team is moving toward "clinical trials in both breast and brain cancer, but it is a slow process." The next step, he says, will be to try to replicate his test-tube results in animals. "No agency in the U.S. would allow me to move forward to clinical trials without some form of proof of concept data in a relevant preclinical in vivo model."
That may be an accurate assessment, but Armentano thinks it's too cautious "given the long established safety of cannabinoids, including THC which is already a legal pharmaceutical, and CBD, which is non-psychoactive, is not a central nervous system depressant and has no risk of overdose."
Not only is there abundant evidence that cannabinoids kill cancer cells, Armentano says, "Investigators now even understand the mechanism of action; in other words, they know how and why cannabinoids kill cancerous cells and halt the spread of malignant tumors."
The question of whether these cannabis compounds can cure cancer in people, he says, "ought to have been already answered decades ago."
