Marijuana cuts lung cancer tumor growth in half

April 17, 2007

Science Daily/American Association for Cancer Research

The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.

They say this is the first set of experiments to show that the compound, Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy.

THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors. The researchers suggest that THC or other designer agents that activate these receptors might be used in a targeted fashion to treat lung cancer.

"The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer," said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.

Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation. Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.

In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines. "When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays," Preet said.

Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.

Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.

Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. "THC offers some promise, but we have a long way to go before we know what its potential is," she said.

The research was presented at the 2007 meeting of the American Association for Cancer Research, held Apr 14-18, 2007 in Los Angeles, CA.

https://www.sciencedaily.com/releases/2007/04/070417193338.htm

Study Finds No Link Between Marijuana Use and Lung Cancer

May 26, 2006

Science Daily/American Thoracic Society

People who smoke marijuana--even heavy, long-term marijuana users--do not appear to be at increased risk of developing lung cancer, according to a study to be presented at the American Thoracic Society International Conference on May 23rd.

Marijuana smoking also did not appear to increase the risk of head and neck cancers, such as cancer of the tongue, mouth, throat, or esophagus, the study found.

The findings were a surprise to the researchers. "We expected that we would find that a history of heavy marijuana use--more than 500-1,000 uses--would increase the risk of cancer from several years to decades after exposure to marijuana," said the senior researcher, Donald Tashkin, M.D., Professor of Medicine at the David Geffen School of Medicine at UCLA in Los Angeles.

The study looked at 611 people in Los Angeles County who developed lung cancer, 601 who developed cancer of the head or neck regions, and 1,040 people without cancer who were matched on age, gender and neighborhood. The researchers used the University of Southern California Tumor Registry, which is notified as soon as a patient in Los Angeles County receives a diagnosis of cancer.

They limited the study to people under age 60. "If you were born prior to 1940, you were unlikely to be exposed to marijuana use during your teens and 20s--the time of peak marijuana use," Dr. Tashkin said. People who were exposed to marijuana use in their youth are just now getting to the age when cancer typically starts to develop, he added.

Subjects were asked about lifetime use of marijuana, tobacco and alcohol, as well as other drugs, their diet, occupation, family history of cancer and socioeconomic status. The subjects' reported use of marijuana was similar to that found in other surveys, Dr. Tashkin noted.

The heaviest smokers in the study had smoked more than 22,000 marijuana cigarettes, or joints, while moderately heavy smokers had smoked between 11,000 to 22,000 joints. Even these smokers did not have an increased risk of developing cancer. People who smoked more marijuana were not at any increased risk compared with those who smoked less marijuana or none at all.

The study found that 80% of lung cancer patients and 70% of patients with head and neck cancer had smoked tobacco, while only about half of patients with both types of cancer smoked marijuana.

There was a clear association between smoking tobacco and cancer. The study found a 20-fold increased risk of lung cancer in people who smoked two or more packs of cigarettes a day. The more tobacco a person smoked, the greater the risk of developing both lung cancer and head and neck cancers, findings that were consistent with many previous studies.

The new findings are surprising for several reasons, Dr. Tashkin said. Previous studies have shown that marijuana tar contains about 50% higher concentrations of chemicals linked to lung cancer, compared with tobacco tar, he noted. Smoking a marijuana cigarette deposits four times more tar in the lungs than smoking an equivalent amount of tobacco. "Marijuana is packed more loosely than tobacco, so there's less filtration through the rod of the cigarette, so more particles will be inhaled," Dr. Tashkin said. "And marijuana smokers typically smoke differently than tobacco smokers--they hold their breath about four times longer, allowing more time for extra fine particles to deposit in the lung."

One possible explanation for the new findings, he said, is that THC, a chemical in marijuana smoke, may encourage aging cells to die earlier and therefore be less likely to undergo cancerous transformation.

The next step, Dr. Tashkin says, is to study the DNA samples of the subjects, to see whether there are some heavy marijuana users who may be at increased risk of developing cancer if they have a genetic susceptibility for cancer.

https://www.sciencedaily.com/releases/2006/05/060526083353.htm