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.
Last year, they published a small study that showed it had a similar effect on mice. Now, the researchers are on the cusp of releasing data, also on animals, that expands upon these results, and hope to move forward as soon as possible with human clinical trials.
"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 along with scientist Pierre Desprez, has been studying the active molecules in marijuana - called cannabinoids - as potent inhibitors of metastatic disease for the past decade.
Like many scientific endeavors, connections made between disparate elements - in this case, a plant considered a controlled substance and abnormal cells dividing out of control - involved a high degree of serendipity. The two researchers were seemingly focused on unrelated areas, but found their discoveries pointing in the same direction.
Desprez, who moved to the Bay Area from France for postdoctoral research in the 1990s, was looking at human mammary gland cells and, in particular, the role of a protein called ID-1.
The ID-1 protein is important in embryonic development, after which it essentially turns off and stays off. But when Desprez manipulated cells in the lab to artificially maintain a high level of ID-1 to see if he could stop the secretion of milk, he discovered that these cells began to look and act like cancer cells.
"These cells started to behave really crazy," Desprez said. "They started to migrate, invade other tissues, to behave like metastatic cells."
Based on that discovery, he took a look at metastatic cancer cells - not just standard cancer cells, but those responsible for aggressively spreading the disease throughout the body. He found the vast majority tended to express high levels of ID-1, leading him to conclude that ID-1 must play an important role in causing the disease to spread.
Meanwhile, McAllister was focused on studying anabolic steroids in drug abuse. McAllister, who also made his way to CPMC from Virginia in the 1990s, became fascinated with the role non-psychotropic cannabidiol, or CBD, interacts with cancer.
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.
About eight years ago McAllister heard his colleague, Desprez, give an internal seminar about his work on ID-1, the manipulated protein cells that masquerade as cancer cells, and metastases. That produced an idea: How effective would cannabidiol be on targeting metastatic cancer cells?
The pair teamed up - Desprez with his apparently cancer-causing ID-1 and McAllister with his cancer-fighting CBD - deciding to concentrate their research on metastatic cells of a particularly aggressive form of breast cancer called "triple negative." It is so named because this type of breast cancer lacks the three hormone receptors that some of the most successful therapies target. About 15 percent of breast cancers fall into this category, and these cells happen to have high levels of ID-1.
When McAllister and Desprez exposed the 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.
"We thought we did the experiment the wrong way," McAllister said. But they got the same results each time they did it.
"I told Sean, 'Maybe your drug is working through my gene,' " Desprez said.
What they found is that the cannabinoid turns off the overexpression of ID-1, which makes the cells lose their ability to travel to distant tissues. In other words, it keeps the cells more local and blocks their ability to metastasize. Cancer kills through its ability to metastasize.
The researchers stressed cannabidiol works only on cancer cells that have these high levels of ID-1 and these do not include all cancerous tumors but, rather, aggressive, metastatic cells. But they've found such high levels in leukemia, colorectal, pancreatic, lung, ovarian, brain and other cancers.
McAllister and Desprez, who hope to publish results of their research before the end of the year, have received various grants through the National Institutes of Health, the U.S. Department of Defense, the California Breast Cancer Research Program and Susan G. Komen for the Cure.
Pot smoking of no help
Still, no one is suggesting that patients with metastatic cancer smoke or ingest marijuana to absorb this potentially cancer-fighting compound.
While cannabidiol, or CBD, is the second-most abundant cannabinoid within marijuana, it has largely been bred out of the plant in favor of a higher percentage of THC, the active chemical that causes the psychotropic high widely associated with the plant.
A long way to go
Martin Lee, director of Project CBD, a Sonoma County group that works to raise awareness of the scientific promise of the compound, described the cannabidiol research as potent both as a medicine and a myth buster.
"It debunks the idea that medicinal marijuana is really about people wanting to get stoned," said Lee, author of "Smoke Signals," a book published last month about the medical and social history of marijuana. "Why do they want it when it doesn't even get them high?"
Lee said the role of marijuana in cancer research is not limited to CBD and that further research needs to be done on how it interacts with THC for possibly greater effect. "While CBD is quite amazing as a molecule, it's really a way of drawing attention to the whole plant," he said.
The researchers know there's a long road ahead as they move from animal studies into human clinical trials and ultimately turning it into a pill or an infused drug that people can take. But they are already developing human trial models and hope to test the drug, probably in combination with current chemotherapies.
"They've been doing studies on mice and showing the effect in tumors. All that is wonderful, but what you don't know is whether it will make people go pea green or colorblind," said Dr. William Goodson, a breast cancer specialist at California Pacific Medical Center who is familiar with the researchers' work.
Nonetheless, Goodson said he is intrigued by the potential to inhibit the factor that makes triple-negative breast and other cancers particularly aggressive. "For people who don't have other options, I think that's an exciting possibility," he said.
Patients with triple-negative breast cancer are eager, too, about the potential of another treatment and hope the research will translate into a drug in the pipeline - sooner rather than later.
Susan Rancourt of San Carlos was just diagnosed with triple-negative breast cancer in July and is in the middle of chemotherapy.
"I don't have doomsday outlook. I feel like I am going to make it through this. But the trick is the next five years," said Rancourt, 59, who is being treated at Stanford. "If this research is advanced to the point of something (a drug) in the next five years, that will make a difference to me."
Sense of immediacy
As for the fact it is derived from marijuana, Rancourt said that's the least of her concerns. "I don't care if it comes from acorns," she said. "It's not the source, it's the result."
Desprez also has a timeline. The researcher learned his 41-year-old sister was recently diagnosed with aggressive breast cancer that has already spread to her lymph nodes. While her cancer is receptive to hormone therapies, he's worried about the potential of recurrence of metastatic disease - one that lacks the hormone receptors and is even more unforgiving.
"I want to be ready for that," he said. "There is a deadline."
The language of cannabis
What is cannabis? Cannabis, also known as marijuana, is a plant from Central Asia that is grown in many parts of the world. In the United States, it is a controlled substance classified as a Schedule I agent, meaning a drug with increased potential for abuse and no known medical use.
What are cannabinoids? Cannabinoids are a class of active molecules in marijuana.
What is THC? The primary cannabinoid and main psychoactive compound in the marijuana plant is delta-9 tetrahydrocannabinol, also known as THC.
What is cannabidiol? Cannabidiol, or CBD, is the second-most abundant cannabinoid within marijuana, but it does not cause a psychotropic high of THC.
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Author: Victoria Colliver
Contact: Contacts at San Francisco Chronicle - SFGate
Website: Pot compound seen as tool against cancer - SFGate