Legal Marijuana Industry Grows Amid Unanswered Questions for Public Health

Two scientists taking part in a session on addiction and pulmonary health outlined existing evidence about marijuana's effects on chronic obstructive pulmonary disease, emphysema, chronic bronchitis, and cancer. But one speaker warned there are too few longitudinal studies in this area.

As legal and social barriers to marijuana fall, what will this mean for public health? What evidence exists about the effects of marijuana on pulmonary health, and what is unknown? Scientists at the American Thoracic Society 2018 International Conference, in San Diego, California, examined these questions Monday during a session on the effects of addiction on pulmonary health.

Smoking marijuana is still smoking, and Donald P. Taskin, MD, of the Division of Pulmonary and Critical Care at the David Geffen School of Medicine at UCLA, examined existing translational research on what the health system could expect if more Americans smoke marijuana legally. He noted that components of marijuana vs tobacco smoke are remarkably similar: 17.6 mg vs 20.2 mg of carbon monoxide and 228 mcg vs 198 mcg of ammonia, respectively, in the gas phase, and 22.7 mg vs 39 mg particulates. Because these 2 plant-bases smoked substance contain many of the same toxic substances—the chief difference being cannabinoids in marijuana and nicotine in tobacco—there is concern that increased marijuana smoking will bring a rise in cancer and chronic obstructive pulmonary disease (COPD), he said.

Bronchoscopic studies of patients who smoke marijuana only show evidence of inflammation, Taskin said, and he showed images where the findings were confirmed by biopsy. The images “show widespread abnormalities very similar to those seen in tobacco smokers,” he said. While there are not many studies, those that exist show physiological changes consistent with chronic bronchitis.

But COPD and emphysema get more complicated. It is clear, Taskin said, that the macrophages are stimulated with smoking, and this causes damage. “You might expect if the macrophage abnormalities seen in marijuana smokers … are similar to those in tobacco smokers there might be increased risk for COPD,” he said. “However, we harvested macrophages for marijuana-only smokers, and compared to macrophages for tobacco smokers and nonsmokers,” Taskin said; the macrophages for the marijuana smokers are “impaired” in releasing co-inflammatory cytokines. There seemed to be “a protective effect” of marijuana—perhaps the tetrahydrocannabinol, or THC. “When we looked at people to find out if there any evidence to suggest that marijuana only smokers may be at increased risk for developing COPD based on a measure of lung function ... we find very little evidence.”

For emphysema, there have only been 2 relevant studies, and they failed to show evidence of the disease. There was slight reduction in specific airway conduction, but not an increase of breathlessness.

“The next question is whether marijuana smoking increases the risk of lung cancer,” he said. “There’s a lot of evidence to suggest that it might.”

Taskin pointed to studies that suggest precancerous changes, including bronchiobiopsies of marijuana-only smokers that show increased expression of biomarkers such as epidermal growth factor receptor (EGFR) and Ki-67, even compared with tobacco smokers. However, 5 of 6 studies have failed to find any increase in lung cancer.

And why would this be? The THC, he said, “has antitumor properties,” including the ability to kill tumor cells before they can grow. The stimulated macrophages have the ability to kill bacteria relative to nonsmokers, and the reduction in coinflammatory cytokines plays a role in regulating nitrous oxide, which has a role in tumor progression.

Researchers recently reanalyzed a cohort of marijuana users with immunocompromised systems—they had HIV—and found no evidence that they had increased risk of pneumonia, Taskin said.

Ellen L. Burnham, MD, of the University of Colorado, in Denver, shared Taskin’s view of marijuana’s role in chronic bronchitis. From there, however, she had a starker view of increased use of the drug, and said that the evidence on marijuana’s connection to COPD and emphysema remains mixed.

Burnham said some patients are interested in the use of cannabis edibles for bronchodilation, and edibles are making up an increasingly large share of the market (as much as 16%). Edibles are “portable, and easy to take to concerts,” she said, but they have a “delayed effect relative to inhaled products.”

In studies, consumers reported “the effects from the drug weren’t felt for a half-hour to an hour after initial consumption, and this has been associated with overdoses as people keep taking the product, to get the effect they think they should be getting.”

Colorful packaging and unknown potency cause people to overdose, and children consume edibles they think are candy. Forms of marijuana that come in a vape pen or a vaporizer have not been studied, and Burnham said, “the allergen potential should be considered.”

“The jury is out,” on whether daily marijuana use will lead to COPD or asthma, because longitudinal studies are still needed. These diseases often start with chronic bronchitis. Federal limits on studying schedule I drugs have made it difficult to do randomized clinical trials. Studies from New Zealand of daily marijuana users who stopped had improvement in bronchitis symptoms, suggesting a link.

“Why is it important to know who is using cannabis for a medical reason rather than a weekend user?” Burnham asked. There are some cannabis activists—particularly medical users—who will not stop using cannabis. They tend to be older and more medically fragile.

With changing marijuana laws, marijuana use is increasing—and so is cannabis use disorder. Surveys show social stigma has eroded, among both teens and adults. In Colorado, where Burnham lives, she said a rise in marijuana tourism has brought more trips to emergency room among first-time marijuana users.

There are many unanswered safety questions, including what pesticides are safe to use. High THC products tend to absorb pesticides at more concentrated levels, and too much is unknown about what is safe to be inhaled.

Burnham noted that government is moving in a direction of tightly regulating tobacco and alcohol, while opening the door to more cannabis users and businesses by letting the industry expand with little regulation.

“What does this mean for public health? The for-profit cannabis industry has a vested interest in increasing daily use, and expanding the number of users,” she said. “As profitability of cannabis grows for these corporations, the legal cannabis industry will have the means to resist changes in public health legislation that might protect consumers.”

As she finished, 3 men in suits seated near the front bolted for the exit.

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