Scientists Unlocking Secrets of Marijuana’s Effects
For seven years, Scott Stokes conducted his own reckless inquiries into the physiological effects of pot.
“I woke up to get high, and I got high to go to bed,” recalled the 19-year-old from El Toro, who broke his marijuana habit only after he was arrested two years ago for burglarizing a head shop. “If I didn’t have it, I would . . . start sweating, and when I’d breathe deep I’d get into these weird breathing patterns.
“People say that marijuana is not addictive, but it’s extremely addictive.”
Science is less emphatic, but research is beginning to show new evidence that Stokes may be right--and to yield other important, sometimes startling insights into how marijuana acts inside the human body. The long years of struggling almost blindly to understand the drug are over; a few monumental discoveries in the past decade have given scientists a much clearer grasp of pot’s effects on the brain, lungs and other systems, showing how it produces euphoria without creating a risk of fatal overdose.
The discoveries confirm one long-standing hunch about marijuana: It is different than other drugs, acting on its own abundant network of chemical receptors. That knowledge has offered the promise of new drug therapies that might someday help correct faulty memories and poor motor coordination. While some scientists toil on those fronts, others are finding out bad news about the damage pot may cause in the lungs and its slightly suppressive influence on the immune system.
“It’s exploding,” UCLA’s Dr. Donald Tashkin said of today’s marijuana research. “Now we have the tools. We should be able to learn more and more about [marijuana] in human and animal physiology.”
Tashkin’s own findings in his work as a research physician are some of the most dire for chronic marijuana smokers. For more than a decade, he has been comparing the lungs of pot smokers, cigarette smokers and nonsmokers, looking for changes in the airways and cellular damage that may lead to lung cancer.
His pool of volunteers--he began with more than 300 marijuana smokers--undergo regular breathing tests and other procedures, including the removal of lung tissue for study in the laboratory. The preliminary findings show that pot smokers who inhale three or four joints a day suffer from chronic bronchitis as often as cigarette smokers who light up a pack or more a day.
In each case, Tashkin said, the pot smoker and the cigarette smoker also show ominous changes in the linings of the trachea and bronchial tubes. At first, the cilia-covered cells that sweep soot out of the lungs begin to die off, replaced by mucous-producing cells and other tissue cells that proliferate far beyond normal. In more than half the volunteers who smoke either marijuana or tobacco, the cells eventually became highly abnormal and skin-like in texture, a condition that doctors consider precancerous.
“The cells are disorganized,” Tashkin said. “It doesn’t mean they’re going to turn into cancer, but it’s on the way to cancer. These changes were as apparent in the marijuana-only smokers and were as common as in the tobacco-only smokers.”
Tashkin, who hopes to publish his findings early next year, said the greatest damage is evident in the lungs of those who smoke both marijuana and tobacco, suggesting the effects may add up or even intensify each other.
“The molecular markers . . . of lung cancer were seen only in smokers, and they were seen mostly in combined smokers of marijuana and tobacco,” he said. “That’s a hypothesis we’re interested in testing . . . that marijuana potentiates the carcinogenic effect of tobacco.”
Marijuana smoke contains many of the same cancer-causing chemicals as cigarette smoke, but a loosely packed, unfiltered joint may deposit four times more tar in the lungs than a cigarette, Tashkin said. In addition, there is evidence that marijuana smoke is more harmful than tobacco smoke to the immune cells in the lungs that attack burgeoning tumors.
“If you harvest those [immune cells] from the lungs of marijuana smokers, they do have an impaired ability to kill tumor-cell targets,” Tashkin said, “and also an impaired ability to kill microorganisms.”
Those findings, which he presented at a recent National Institutes of Health symposium on marijuana, are also considered preliminary, he said.
Brain Has Special THC Receptors
Other apparent breakthroughs in understanding marijuana’s effects on the brain date back to 1988, when Allyn Howlett of St. Louis University discovered the chemical receptors that react to delta-9 tetrahydrocannabinol (THC), the compound in marijuana that produces a high.
Until the receptors were found, some scientists speculated that pot, like alcohol, was a “dirty” drug, producing its effects by gumming up the works inside any number of cells and systems. The existence of the receptors proved otherwise, providing a window into how marijuana works and setting it apart from any other kind of substance, including heavily addictive drugs such as heroin and morphine.
“It’s completely different from all the other drugs,” said Miles Herkenham, a brain researcher at the National Institute of Mental Health in Bethesda, Md., who helped map the location of the so-called cannabinoid receptors in the early 1990s.
Cells embedded with the receptors are inhibited from functioning when exposed to the THC molecule. Scientists theorize that the natural purpose of the receptors may be to help regulate other systems in the body’s complex network of checks and balances.
Cannabinoid receptors are concentrated most heavily in the cerebellum, the part of the brain that controls motor coordination, and in the hippocampus, which governs learning and memory. Large numbers are also found in the cerebral cortex, the seat of higher thinking, and lesser numbers are scattered in the immune system. They are largely absent from the brain-stem regions that govern heartbeat and respiration.
The imbalance enables scientists to account for the loss of coordination and the distorted perceptions that are characteristic of a marijuana high.
Pot’s influence on the immune system seems relatively subtle, Herkenham said. In those whose immune responses are already poor, marijuana could perhaps be harmful, he said. However, advocates of marijuana use in medicine say it helps to reduce pain and nausea and stimulate the appetites of AIDS and cancer patients--benefits that may far outweigh its downside.
“The paucity of receptors in the brain stem is crucial for explaining why it’s a ‘safe’ drug,” Herkenham added. “It’s impossible to take a lethal overdose. You absolutely cannot kill an animal with THC.”
Locating the receptors has given scientists far keener insights--but no clear answers--in their efforts to determine whether marijuana is addictive, a question that is still hotly debated. Usually, drugs that produce an intense craving--heroin, cocaine, morphine and nicotine, for example--act upon receptors in the dopamine system, a circuit that regulates nerve activity in the brain, Herkenham said.
“There’s a theory that any drug of abuse affects the dopamine system,” he said. “Marijuana does not. There are no THC receptors on these dopamine cells. It explains why there’s no such thing as . . . a [marijuana] craving where people will basically kill to get their drugs. You don’t get that with marijuana.”
Still, some scientists suggest that if dopamine receptors can become accustomed to a chemical high, so can cannabinoid receptors, even if the result is more subtle.
Evidence that marijuana is addictive has been elusive in part because THC is readily stored in body fat. Pot smokers who quit are often weaned off the drug slowly as small amounts continue to filter into the bloodstream.
Dr. Reese Jones of UC San Francisco explored the issue with a multimillion-dollar hospital study 15 years ago. He isolated more than 100 heavy marijuana users and gave them THC pills every four hours, around the clock. After a few days, some of the volunteers were given identical-looking placebo pills containing no THC.
“They’d become irritable, restless, really jittery,” Jones said. “They developed some nausea, diarrhea . . . flu-like symptoms . . . sleep disturbances, weight loss, sweating. Everybody [given the placebo] showed these things to a degree, some more than others.”
Jones’ study--which is still cited today by some of his colleagues--was rejected at the time by major science journals. Critics said the THC doses were far higher than a pot smoker would normally ingest. Critics also noted that the subjects showed no seizures, no psychoses, none of the symptoms that were associated with withdrawal from opiate drugs. No one in those days knew anything about cannabinoid receptors.
“It didn’t fit the common beliefs,” Jones said.
A few years ago, further research grew out of another significant advance: Scientists discovered a compound that prevents THC from binding to the receptors. The blocking compound made it possible for researchers to shut off THC’s effects on the brain almost as if they were turning off a water spigot, despite THC’s presence in fat tissue.
The discovery enabled Dr. Billy Martin of Virginia Commonwealth University to demonstrate what he called “a dramatic withdrawal” in laboratory rats. Martin and Dr. Michael Walker of Brown University performed almost identical studies, producing a variety of bizarre rodent behaviors, in 1994.
“I firmly believe marijuana produces dependence,” Martin said. In the real world, people who quit smoking pot may not realize they are going through withdrawals; they may think they are catching the flu. But occasionally, Martin said, some call him for advice, aware of his research. One man even asked recently if there was a patch for marijuana, as there is to help cigarette smokers break the nicotine habit.
The National Institute of Drug Abuse, which funds most of the marijuana research in the United States, estimates that 100,000 people seek treatment every year for pot dependency.
The Phoenix House, one of the nation’s largest private, nonprofit drug-treatment organizations, completed a survey this fall of 223 teenagers living in its residential centers in Los Angeles, Orange and San Diego counties. Four of every 10 teenagers had entered the program because of marijuana use, said Dr. Mitchell S. Rosenthal, president of the organization.
“There is an unfortunate tendency among even the most reasonable, otherwise law-abiding citizens to underestimate the dangers of marijuana,” Rosenthal said.
Yet marijuana research has been plagued by decades of emotionalism and politics. Scientific disclosures about the drug’s purported effects on memory, human reproduction and childhood development have been nebulous in many cases, inviting any number of interpretations. Even scientists complain that some results are hyped, twisted, or based on sketchy data.
Some scientists--especially those funded by sizable federal grants--are reputed to be “anti-marijuana.” A rival camp--those perceived as soft on pot--insist that only politics and hysteria have kept marijuana designated as a “class one” drug, unsuited to any legitimate purpose and more dangerous, by federal government standards, than morphine.
“People have their beliefs about marijuana,” said Jones, the UC San Francisco researcher. “Even as a scientist, when you get up at a meeting, [other scientists] wonder, ‘Is he for or against it?’ ”
Scientific bickering, political debate and contradictory reports in the mainstream media have caused widespread confusion among teenagers and adults alike. Although some teens profess to know, or suspect, that marijuana can be harmful, others believe just the opposite.
“Marijuana can actually be really good for you,” said Debbie, 15, a sophomore at Mira Costa High School in Manhattan Beach. Like other minors quoted here, her name has been changed. “I smoke it if I’ve got really bad migraines or cramps, or I’m overtired and can’t get to sleep. It gives you a really deep sleep.”
Debbie was cynical about the scientific research into pot: “They’re lying to us. Smoking and drinking are much worse for you than marijuana. Nicotine will give you lung cancer. Drinking hurts your liver. . . . . No one has ever died from marijuana.”
As an afterthought, based strictly on her personal observations, she said, “It will make you dumb or lazy if you use it every day. I know that for a fact, because some of my friends do.”
Effects on Motivation, Memory Still Unclear
Scientific studies of marijuana’s effects on motivation and memory have been a “can of worms,” scientists said, although one researcher now claims to have evidence that heavy pot smokers perform more poorly on psychological tests than light smokers, even when both groups are sober.
Those findings were based on two groups of college students who were tested 24 hours after their last puff of marijuana, said Dr. Harrison Pope, who conducted the research at McClain Hospital in Belmont, Mass.
Pope, who is now studying marijuana smokers who have been off the drug for a longer period--a month--is not sure how to account for the results. They may indicate a withdrawal effect, or that THC lingers in the brain, or that heavy users actually suffer some mild brain damage, he said.
“You’d think by now we would have some idea which,” he said. “It’s a testimony to how little we know. We’re trying to find these fundamental things relatively late in the game.”
A few teenagers who said they used pot heavily noticed a difference in themselves.
“Your comprehension is down, your motivation is down. I look back on myself when I used to smoke pot and I realize how childish I was,” said Joshua Miller, 18, who stopped using marijuana because of fears for his health. “I see these kids . . . they used to be intelligent. One friend of mine . . . got kicked out of math. He couldn’t comprehend.”
Andy, 17, shrugged off the drug’s effects, saying, “I don’t think it screws you up that bad. It burns the cilia off your throat--that’s not good. I’ve been smoking for a couple years now and the only thing I’ve noticed is a little bit of short-term memory loss.”
While science is making progress toward understanding marijuana, science is also making marijuana more potent.
Hybridizing and special growing techniques have enabled dealers such as Hemp BC, a cannabis store based in Vancouver, British Columbia, to offer 70 or more varieties of marijuana seeds. Customers can purchase them by catalog or over the Internet and grow pot that is far more potent than the marijuana of the 1960s, said Marc Emery, the store’s founder.
Thirty years ago, pot typically contained 3% to 5% THC and quality control was poor: Leaves were often stored in hot, dry places and mishandled before reaching consumers, Emery said. Today, low-grade pot is still widely available, but top-quality “sinsemilla” plants now contain up to three times as much THC, and the potency is protected by means of opaque storage bags and freezing, Emery said.
The new “bud” has raised concern on both sides of the political spectrum.
Dr. Alex Stalcup, one of the founders of the Haight-Ashbury Clinic, which offers treatment for substance abuse, said the new pot should be looked at as a new drug.
“The most addicting quality a drug can have is the ability to produce . . . an explosive rush of euphoria,” said Stalcup, now a physician at the New Leaf Treatment Center in nearby Concord. “I see kids now who are stoned from the moment they wake up--the first thing they do is reach over and take a bong hit--until they go to sleep at night. They don’t seem to ever have a sober moment.”
The Marijuana Policy Project, a Washington-based organization, advocates legalizing the drug, in part to keep men and women from going to prison for using it.
Though skeptical of much of the scientific research, leaders of the organization believe more effort should be directed at keeping teenagers sober, said spokesman Chuck Thomas.
“Kids should not use marijuana at all, period,” Thomas said.
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Lung Damage from Pot
Long-held hunches about the effects of prolonged marijuana use are giving way to scientific evidence that the drug can be harmful. Dr. Donald Tashkin of UCLA has studied the lungs of several hundred pot smokers, tobacco smokers and nonsmokers for more than 10 years, and has discovered that three or four joints a day--considered heavy use--can be as damaging in some ways as a pack or more of cigarettes. Here are some of his findings.
TOP PHOTOS:
1. Brochial tubes of a non-smoker, left, show healthy pink tissues and clearly defined, unobstructed passageways.
In those of a marijuana smoker, center, and a tobacco smoker, right, the tissues are reddish and swollen, and the passageways are partially obstructed by mucus.
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2. The body’s major air passages are lined with ciliated tissues that help to remove foreign particles from the lungs and trachea. In this cross-section, healthy tissues are lined with hair-like cilia that sweep away dust and soot, and the cells beneath are normally developed.
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3. As airways become damaged from marijuana or tobacco smoke, the cilia disappear, replaced by an abundance of mucous cells, stained pink in photo.
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4. In badly damaged airways, the tissue linings become skin-like in texture, and cells beneath the mucous cells proliferate wildly, a condition that may lead to cancer.
Fighting Lung Tumors
Chart measures the ability of various test subjects to fight off the formation of lung tumors, based on the ability of the subjects’ macrophages--cells that form part of the body’s immune defense--to kill tumor cells.
Cells from the non-smoking control group showed a slightly greater ability to kill tumor cells than those from tobacco smokers. Marijuana smokers exhibited far less resistance to tumors, and cocaine smokers showed the least.
Effects on Respiratory Symptoms
Chart shows frequency of minor lung problems in volunteer test subjects. Non-smokers showed far fewer symptoms than those of tobacco smokers, marijuana smokers or smokers of both marijuana and tobacco. Tobacco smokers showed more coughing, wheezing and sputum production than pot smokers, but pot smokers showed more instances of chronic bronchitis.
Source: Dr. Donald Tashkin, UCLA
