Marijuana is the most widely used illicit drug in the country -- an estimated 25 million Americans smoked it within the last year and close to 100 million have smoked it at least once in their life, according to the most recent National Survey on Drug Use and Health by the federal Substance Abuse and Mental Health Services Administration.
Rates and severity of marijuana addiction pale in comparison to that of legal addictive drugs, alcohol and nicotine, according to the Advisory Council on the Misuse of Drugs, a panel of independent experts advising the British government, in a rare head-to-head, scientific comparison.
Yet, the fact is, recreational use can lead to addiction, and inhaling marijuana smoke is unhealthful for the lungs. Some researchers argue that marijuana may predispose heavy users to mental illnesses such as psychosis and depression.
How big are these risks and how should they be measured against health benefits? "The FDA has ruled that marijuana has no medical benefits, but its harms are well known and proven," says Tom Riley, a spokesman for the White House Office of National Drug Control Policy, referring to an April 2006 statement released by the FDA and several other federal agencies concluding that smoking marijuana was not of medicinal use.
For comparison's sake, Riley cites the prescription drug Vioxx. The FDA, he notes, pulled Vioxx off the market in spite of its proven efficacy, because it created problems in a small number of people.
Then, too, the number of people adversely affected by marijuana use is large, Riley says. "There are more teens in drug treatment for marijuana dependence than for alcohol or any other drug," he says.
Marijuana is a Schedule 1 drug by the Drug Enforcement Administration's Controlled Substances Act, a classification reserved for drugs carrying the highest risk for addiction and no medical benefit.
Scientists have reviewed the weed's risks and find them to be real, but small. Ten years ago, the Institute of Medicine reviewed the scientific evidence about marijuana at the request of the Office of National Drug Control Policy. The 1999 report states that, "except for the harms associated with smoking, the adverse effects of marijuana use are within the range of effects tolerated for other medications."
In February, the American College of Physicians, the nation's second-largest physicians group, released a position paper in support of medical-marijuana research, protecting doctors from criminal prosecution and rescheduling marijuana as a less harmful drug.
A British advisory group this year found no evidence to reclassify cannabis as a more harmful drug in that country. In contrast to the U.S., the U.K. puts cannabis in the lowest category (Class C) in terms of criminal penalties for possession or sale, although government officials are campaigning to move it to Class B.
To investigate the risks of marijuana, researchers typically use heavy marijuana smokers as subjects. Though such a study design may be convenient, it makes interpretation tricky because heavy users may have traits in common besides smoking pot. Thus, says psychologist and marijuana researcher Stanley Zammit of Cardiff University in Wales, it is not easy in these kinds of studies to separate out the contribution of marijuana to any measurable effect in the group.
Claims of a link between marijuana use and psychotic episodes came under scrutiny after the U.K. downgraded cannabis from Class B to Class C in 2004. In 2007, Zammit was asked by England's Department of Health to survey the existing evidence to determine the long-term risks for mental illness from using cannabis. After researching the literature and including only those studies that satisfied certain criteria, he combined the results in a 2007 Lancet paper.
He concluded that marijuana use was associated with an increased risk of psychosis -- ranging from self-reported symptoms such as delusions or hallucinations to clinically diagnosed schizophrenia.
The risk is small, he adds. Cannabis use was associated with a 40% increase in risk overall and up to a twofold increase in heavy users. Because the risk of any person developing psychosis in their lifetime is about 2% to 3%, cannabis use at worst increases that to 5%. "So 95% of the people are not going to get psychotic, even if they smoke on a daily basis," Zammit says.
Zammit adds that "the main limitations of these studies is that you can never be sure that it's the cannabis itself that's causing this risk." Heavy users of marijuana may differ from nonusers in other traits -- including those that lead independently to increased drug use and risk of psychosis. The studies he reviewed tried to take into account this possibility but could not rule it out entirely.
The bottom line? "The evidence is probably strong enough that people should be aware of this risk," he says.
Even if it's real, the risk of developing psychosis because of marijuana use is smaller than with use of some other drugs -- including legal ones such as cigarettes, says Mitch Earleywine, a psychologist at the State University of New York University at Albany.
Grant says that numbers of schizophrenia cases have not increased since before the 1960s, when widespread marijuana use began. "The data are variable to be sure, but most studies have found that over the years the rate of schizophrenia has been stable or even declining," he says.
In an American Journal of Psychiatry study, 1,920 adults were assessed for marijuana use and depression and followed for 15 years. In those subjects who had no depressive symptoms at the study's start, marijuana abusers were four times more likely to develop depressive symptoms down the road. But Zammit, who reviewed this paper and 23 others in his 2007 Lancet paper, says the data overall are even murkier than for psychosis. Most of the studies he reviewed did not assess symptoms of depression before marijuana use, and so didn't rule out the idea that depression makes someone more likely to smoke marijuana -- and not the other way around.
A review of the scientific literature published in the Journal of the International Neuropsychological Society in 2003 looked at whether marijuana smoking had lasting effects on cognition after THC has left the body. Marijuana use was found to have small effects on memory in long-term users -- measured by asking subjects to recall words, for instance -- but no differences were seen on attention, verbal skills and reaction time. "We were actually surprised," says Grant, an author on the study. Even if the marijuana itself wasn't causing such things, he expected marijuana users might have other less-than-healthful behaviors -- they may drink a bit more, or use some other drugs, and "you might expect them to do a little worse."
A 2002 study published in the Journal of the American Medical Assn. found that a group of 51 heavy marijuana users (two joints per day) recalled two to three fewer words on average than nonusers in a memory test with a list of 15 words.
A second study, published in the Archives of General Psychiatry in 2001, found a similar deficit in 63 daily marijuana smokers who hadn't smoked for up to a week. After 28 days of not smoking marijuana the effect disappeared.
Studies on brain function and mental illness cited above were conducted in adult marijuana users. How the drug affects adolescents is not completely resolved, but the data are more troubling.
A 2000 paper in the Journal of Addictive Diseases recruited 58 marijuana users and found structural changes in the brains of those who had starting smoking marijuana before age 17 but not in those who didn't start smoking until they were older.
"There's also a modest decrease in IQ if teens use heavily, though weekly users and folks who quit don't seem to show it," Earleywine says. Adolescence, he says, is a time when brain neurons are making oodles of new connections, and it's possible that a psychoactive drug such as marijuana may adversely influence that process.
Before it has any effect on the brain, marijuana smoke enters the body through the lungs. Dr. Donald Tashkin, professor of medicine at the UCLA David Geffen School of Medicine, has studied the pulmonary consequences of marijuana use for 25 years, recruiting a group of 280 heavy habitual pot smokers in the early 1980s, including some who also smoked cigarettes. (Subjects averaged three joints per day for an average of 15 years.) For comparison, he also recruited cigarette smokers who didn't use marijuana and people who didn't smoke anything.
Tashkin has done a number of studies over the decades comparing these groups. "I began with the hypothesis that regular smoking of marijuana would have an impact on the lungs qualitatively similar to the impact of regular tobacco smoking," he says. That's because the smoke of both plants are more similar than different.
Tashkin and his colleagues did find symptoms of chronic bronchitis in his marijuana-smoking group. In a 1987 study in the American Review of Respiratory Diseases, they reported that incidence of chronic cough, sputum production and wheezing was similar to that in cigarette smokers.
In a second study in the same subjects published in the American Journal of Respiratory and Critical Care Medicine in 1998, examination of the airways and the cells lining the airways found swelling, redness and increased secretions in marijuana users. Biopsies showed "extensive, widespread damage to the mucosa," Tashkin says, similar to what was seen in tobacco users. "This is amazing, because the marijuana smokers average three joints a day, but the tobacco controls smoked 22 cigarettes, suggesting that on a cigarette-to-cigarette basis, marijuana may be more damaging."
But marijuana smokers differ from tobacco smokers in other, potentially more important ways, Tashkin adds. They do not seem to develop more serious consequences of cigarette smoking, namely chronic obstructive pulmonary disease (COPD) -- the fourth leading cause of death in the U.S., killing 130,000 people each year -- or lung cancer, the most common cancer in Americans and responsible for an additional 160,000 annual deaths, according to 2005 statistics from the Centers for Disease Control and Prevention.
To study lung cancer, Tashkin looked at more than 600 lung cancer patients and more than 1,000 control patients matched for age, socioeconomic class, family history and other alcohol and drug use (along with many other potential influences).
The results, published in a 2006 paper in Cancer Epidemiology Biomarkers and Prevention, found a large number of regular marijuana smokers were present in both groups, but statistically there were no more in the cancer group than control group, suggesting no association between marijuana use and lung cancer. Tobacco smokers, on the other hand, showed a dose-dependent increase in risk: with a 30%, 800% and 2,100% increased risk of lung cancer in those who smoked less than a pack, one to two packs or more than two packs per day, respectively.
Other studies have found increased cancer risk. A study of 79 lung cancer patients and 300 controls published in the European Respiratory Journal this year found a fivefold increased risk in the heaviest marijuana users (daily use for 10 years) and no effect in less heavy users.
But Tashkin says this conflicting report was much smaller in scale, having fewer than 20 subjects in the group of heaviest marijuana users. "My critique would be: It's a small study. I think that their small sample size is responsible for vastly inflated estimates," he says. --
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Vapor versus smoke
Smoking anything is perceived as bad these days, says Dr. Donald Abrams, chief of hematology and oncology at San Francisco General Hospital and professor of clinical medicine at UC San Francisco. And so he devised a pilot study to evaluate a novel inhalation method conducted in 18 otherwise-healthy subjects. "We used a device that heated cannabis below the point of combustion -- basically, a heating element and a fan. The fan filled up a balloon from which the patients could inhale," Abrams says.
The findings, published in Clinical Pharmacology and Therapeutics in 2007, showed that levels of THC were "virtually identical," as were patients' reports of subjective "high." No increase in exhaled carbon monoxide was observed with vaporized marijuana, as was the case with smoked marijuana, and patients preferred vaporization to smoking.
"The fact is that whole marijuana, particularly when vaporized and not smoked, is a safe and effective delivery system," says psychiatrist Dr. Igor Grant, director of the UC Center for Medicinal Cannabis Research in San Diego.
-- Jill U. Adams