Depending on whom you ask, marijuana is a dangerous drug that
should be kept illegal alongside heroin and PCP, or it's a
miracle herb with a trove of medical benefits that the government
is seeking to deny the public -- or something in between: a plant
with medical uses and drawbacks, worth exploring.
As the political debates over medical marijuana drag on, a small
cadre of researchers continues to test inhaled marijuana for the
treatment of pain, nausea and muscle spasms.
All drugs have risks, they point out -- including ones in most
Americans' medicine cabinets, such as aspirin and other
pain-relievers or antihistamines such as Benadryl. Doctors try to
balance those risks against the potential for medical good -- why
not for marijuana as well, they ask.
The truth, these researchers say, is that marijuana has medical
benefits -- for chronic-pain syndromes, pain, multiple sclerosis,
AIDS wasting syndrome and the nausea that accompanies
chemotherapy -- and attempts to understand and harness these are
being hampered. Also, they add, science reveals that the risks of
marijuana use, which have been thoroughly researched, are real
but generally small.
Dr. Donald Abrams, chief of hematology and oncology at San
Francisco General Hospital and professor of clinical medicine at
UC San Francisco, says he sees cancer patients in pain, not
eating or sleeping well, experiencing nausea and vomiting from
treatment, and being depressed about their situation. He says he
is glad that he lives in California, where use of medical
marijuana is allowed by state law, although federal officials
continue to raid cannabis dispensaries in the state and
scrutinize practices of physicians who specialize in writing
cannabis recommendations for patients.
"I can talk to patients about medicinal cannabis [and] I'm often
recommending it to them for these indications," Abrams says.
Pro marijuana: A balm for pain
Medical marijuana use has a history stretching back thousands of
years. In prebiblical times, the plant was used as medicinal tea
in China, a stress antidote in India and a pain- reliever for
earaches, childbirth and more throughout Asia, the Middle East
In recent decades, medical researchers have investigated
marijuana's effects on various kinds of pain -- from damaged
nerves in people with HIV, diabetes and spinal cord injury; from
cancer; and from multiple sclerosis. Marijuana has also been
hypothesized to help with nausea induced by chemotherapy and
antiretroviral therapy, and with severe loss of appetite as seen
in people with the AIDS wasting syndrome.
The weed's actions are due to the active ingredients
tetrahydrocannabinol (THC) and some 60 other cannabinoids, which
mimic the action of chemicals -- known as endogenous cannabinoids
-- that exist naturally in the brain. Those cannabinoids activate
receptors in our nerves, triggering physiological responses.
A legal prescription form of THC (Marinol) exists, yet
researchers say it's far from a perfect drug. Taken orally, its
absorption is highly variable and unpredictable and often
delayed, says Dr. Igor Grant, a UC San Diego psychiatrist who
directs the university's Center for Medicinal Cannabis Research.
"Smoking is a very efficient way to deliver THC," he says.
As a result of its federally illegal status, medicinal use of
marijuana is restricted to carefully vetted clinical research
studies or to patients in states such as California that have
passed laws to allow for personal medical use. Research on the
medicinal use of marijuana relies on government-issued marijuana
cigarettes, which come in different strengths and are supplied by
the National Institute on Drug Abuse.
The UC Center for Medicinal Cannabis Research in San Diego helps
coordinate clinical studies to investigate the safety and
effectiveness of marijuana. Here's what they've found.
Recent research suggests that marijuana can assuage this
chronic-pain syndrome in which burning sensations occur and
simple touch can feel like hurt. It is unaffected by aspirin-like
drugs and fairly resistant to stronger analgesics such as
In a 2007 study on neuropathic pain related to HIV infection, 50
patients smoked marijuana cigarettes three times a day or
marijuana cigarettes from which active ingredients had been
extracted. Subjects then rated their pain on a scale ranging from
"no pain" to "worst pain imaginable." The results, published in
the journal Neurology, showed a 34% reduction in ratings of pain
in the marijuana group compared with 17% in the placebo group
over five days of treatment.
Another study in 44 patients reported in June in the Journal of
Pain found that marijuana alleviated neuropathic pain arising
from a variety of conditions, including spinal-cord injury and
diabetes. Participants smoked marijuana on a set schedule --
first two puffs, then three puffs an hour later, then four puffs
an hour after that -- from a single cigarette containing either
0%, 3.5%, or 7% THC. Average pain ratings before smoking were 55
on a 100-point scale and decreased by 46% in both treatment
groups and by 27% in the placebo group one hour after the last
Analgesic drugs are often tested against experimentally induced
pain. Such studies have been conducted for marijuana too. In one
2007 report in the journal Anesthesiology, 15 healthy volunteers
received skin injections with capsaicin -- the chemical behind
that fiery spice in chile peppers -- and then smoked
different-strength marijuana cigarettes. The medium dose, with a
4% THC concentration, lessened the burning pain.
These three pain studies all concluded that smoked marijuana can
bring relief to sufferers of neuropathic pain comparable to other
analgesic drugs. It is not a cure, Grant says: "It's like other
pain medicines, you have to keep taking it."
Study subjects did feel high, an effect that varied among
individuals. Marijuana also affected thinking, shown as problems
with tasks of memory and complicated reasoning after the
strongest marijuana cigarettes were used. Potentially
problematic, these effects were tolerated by subjects -- no one
opted out of the study because they couldn't think straight.
Grant says it's important to have a choice of treatments because
not everyone responds to or can tolerate the available drugs.
Antidepressants are used for neuropathic pain but cause dry
mouth, constipation and urinary problems, and must be avoided by
people with conditions such as glaucoma. Others can't take
aspirin-like drugs. "Having an alternative compound is always
good," Grant says.
Patients with multiple sclerosis suffer muscle spasms, pain and
tremor. Anecdotal reports suggest that marijuana may be helpful,
but controlled studies are few. One, presented at an April
meeting, had 51 multiple sclerosis patients smoke 0% or 4% THC
marijuana cigarettes daily for three days. Intensity of spasms
was reduced by 32% and pain ratings by 50% after smoking
marijuana, compared with 2% and 22% reductions after placebo
cigarettes. Five subjects withdrew, citing side effects: feeling
too high, dizzy or fatigued.
Other studies in patients with multiple sclerosis used a cannabis
extract that can be taken orally. In a 2007 European Journal of
Neurology study, nearly half of 184 patients experienced at least
30% improvement in muscle spasms.
But a 2004 Neurology paper showed no reduction in objective
measures of arm tremor with cannabis extract, although five
subjects out of 13 reported feeling improvement. This might have
resulted from mood-altering effects of the drug or from some
aspect of tremor not measured.
A 2008 review published in the European Journal of Cancer Care
analyzed 30 clinical studies using cannabinoid drugs synthesized
in the lab and concluded that they were better than standard
antinausea drugs in alleviating the nausea and vomiting that
accompanies chemotherapy. One such drug is Marinol, a THC
preparation approved by the Food and Drug Administration for
precisely this purpose.
Survey studies suggest that some people with HIV smoke marijuana
to counteract nausea caused by antiretroviral therapy.
Researchers at the UC Center for Medicinal Cannabis Research have
tried to study the effect of smoked marijuana on nausea and
vomiting in patients undergoing chemotherapy but have struggled
to enroll enough subjects, Grant says.
Bruce Mirken, director of communications for the Marijuana Policy
Project -- a group that lobbies for the decriminalization of
marijuana -- says he is all for research on the chemical
components in marijuana with the goal of making more-purified and
perhaps more-targeted drugs that do not deliver a "high," but
does not see "criminalizing use of that plant by people who are
ill when you are making its main psychoactive ingredient legal in
the form of a very expensive pill."
Tom Riley, a spokesman for the White House Office of National
Drug Control Policy, says marijuana advocates are seeking a free
pass. "They want to be exempted from the regular [drug] approval
process," he says.
Con marijuana: Damaging habit?
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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.