by Victoria Colliver
(left) and Sean McAllister have been
marijuana's active molecules as potential disease inhibitors.
Photo: Carlos Avila
Gonzalez, The Chronicle / SF
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
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.
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 -
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
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
Marijuana's better known cannabinoid - delta-9 tetrahydrocannabinol,
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
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
"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.
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
the National Institutes of Health
the U.S. Department of
the California Breast Cancer Research Program
Susan G. Komen for the Cure
Pot smoking of 'no
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
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
"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.
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."
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
Desprez also has a
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."
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.
cannabinoids? Cannabinoids are a class of active molecules
primary cannabinoid and main psychoactive compound in the
marijuana plant is delta-9 tetrahydrocannabinol, also known
Cannabidiol, or CBD, is the second-most
abundant cannabinoid within marijuana, but it does not cause
a psychotropic high of THC.