KEY QUESTIONS CLOUD MEDICAL POT DEBATE

TAMPA - On the fourth floor of a hivelike, 1970s-vintage lab building
on the University of South Florida's medical campus, Thomas Klein has
spent 25 years studying marijuana's effects on the immune systems of
mice, blowfish and human beings.

If anyone should be able to answer the question that has surrounded
pot for decades -- How bad is it for you? -- it should be Klein.

Klein, 66, a tall, courtly professor of immunology and molecular
medicine, can tell you he is very close to solving a few puzzles
about the connection between cannabinoids -- the active compounds in
marijuana -- and common allergies. But like other researchers in the
field, Klein says marijuana's health effects remain a daunting mystery.

Solving that mystery grows more urgent as efforts to legalize
marijuana, at least for medical use, gain momentum. Arizona this
month became the 15th state to make it possible for adults to get a
doctor's prescription for marijuana. Add to this an estimated 15.2
million illicit users across the country -- including Florida, where
the drug remains illegal in all cases, but also readily available.

Unlike alcohol and tobacco, proponents say, marijuana has not been
proven to be a danger to users or to society. Instead, they say, it
can relieve pain and treat other medical problems, with fewer side
effects than many legal drugs.

To which scientists like Klein respond: The jury's still out.

"We used to think it affected your brain," Klein said. "Now we know
it affects all the cells in your body. It won't kill you, but it will
change your immune system. Over time, some of these changes might not
be beneficial."

One reason that marijuana's effects remain hard to quantify is that
it affects people differently. Almost anyone who drinks several shots
of vodka will be intoxicated. But not everyone who smokes a joint
becomes stoned. Some just become more relaxed.

The health risks and benefits also vary greatly.

Scientists agree that as a medical treatment, marijuana has shown to
ease excruciating pain from arthritis to bone cancer. It also
benefits some patients suffering from glaucoma or AIDS-related weight
loss. But others get no benefit at all, and no one yet knows why.

The effects on recreational users are even less understood. Studies
of habitual smokers remain small, underfunded and cumbersome to pursue.

Dr. Bruce Robinson, a Sarasota gerontologist and an expert on
dementia, said marijuana appears to cause short-term memory and
lapses in cognition. It has also been linked to "amotivational
syndrome" -- which might, in laymen's terms, be described as the
inability to get off the couch and get a job.

But, unlike with alcohol, there is no strong evidence that "marijuana
produces permanent deficits in memory and thinking."

"Alcohol is a much more dangerous drug," Robinson added.

Deterring Research

Another reason that marijuana is not as well understood is that it
has been the subject of fewer studies than many other drugs.

Pot remains classified as a Schedule I controlled substance -- which
basically defines it as a dangerous drug with no medical value. This
alone deters scientific study, said Dr. Igor Grant, director of the
Center for Medicinal Cannabis Research at the University of
California, San Diego.

"My view is that the federal government should reschedule marijuana,
and that would stimulate research," Grant said. "Right now, it's too
difficult to fool around with a Schedule I drug. You have to go
through all these regulatory steps."

According to a search of the National Library of Medicine's PubMed
database, the number of journal articles on the subject went from 258
in 1996 to 2,603 in 2009. But a similar search for work on aspirin
last year yielded more than 7,000 articles. For steroids, the number
topped 97,000. And most of the pot research, Grant said, involves
small samples of patients.

"The next step is to do a larger study," he said. "I think it's fair
to conclude that cannabis can be useful, that it can be another arrow
in the quiver to treat difficult conditions."

But, he added, "We don't know how elderly people respond as opposed
to middle-aged people. What if there are complicating conditions? We
know cannabinoids can speed up your heart, for instance, and lower
the blood pressure. What will that do over time? We don't know."

Medical marijuana activists counter that the federal government does
not want to know. Irvin Rosenfeld, 57, of Fort Lauderdale is one of
four surviving subjects of the National Institute on Drug Abuse's
unusual "compassionate use" program, begun in 1978 in response to
legal appeals by individual patients. The program closed to new
patients in 1992.

Every 25 days, Rosenfeld receives 300 marijuana cigarettes from the
government, grown and rolled at the University of Mississippi, home
to NIDA's Marijuana Project at the National Center for Natural
Products Research. He has been smoking at least 10 a day since 1982
to control a rare and once-disabling bone disorder. But NIDA, he
said, has shown no interest in studying the human volunteers in this
unusual long-term trial that it continues to fund.

"You would think so, wouldn't you?" Rosenfeld asked. "That's as far
from the truth as can be. The federal government doesn't want to know
that cannabis works. Even though my doctor fills out reports twice a
year, nobody reads them."

USF's Klein explained why cannabis has a unique impact on each individual.

"In some people the drugs are metabolized differently," he said.
"Their receptors for the drug might be a little bit different." For
pot to help, he said, "you ingest the drug and it has to get to the
right receptors, and those receptors have to be there and functioning
in a certain way, so that you have X amount of the drug and 20X
amount of effect. These are all the differences that we have just
begun to appreciate."

Medical Benefits

Science has yielded some reliable conclusions about pot's benefits.
Grant's institute has backed up other studies on its usefulness in
combating neuropathy, which he described as a "dull, burning pain."
Since nerve pain is so resistant to available drug therapies,
marijuana's potential here is significant, said Klein.

"We read about this in the newspaper and say, 'Well, we all have pain
from time to time,'" he said. "But real, chronic neuropathic pain can
be debilitating."

Other conditions where marijuana has proven of some help include
glaucoma, multiple sclerosis, Parkinson's disease and the nausea that
attends chemotherapy. Sufferers from ALS, or Lou Gehrig's disease,
have found relief, and cannabis has proven so good at dulling the
aches and pains that come with age that some policy analysts predict
it will become the drug of choice as baby boomers begin to populate
nursing homes.

In most cases, smoking pot seems to work better than ingesting it
orally. But large studies have linked long-term marijuana habits to
lung damage.

"There are some people who will argue that smoking is never going to
be an acceptable way to deliver a medicine," Grant said. "At the
moment, smoking is one of the practical delivery systems. This has to
do with the unusual absorption and distribution effects of cannabis
when taken by mouth; it's very difficult to zero in on the exact
right level. If you're smoking, you can control how quickly you're
inhaling, and stop smoking once you start getting the effect."

Grant and Klein said studies are under way to determine whether
vaporizing cannabis -- so that it can be inhaled without combustion
- -- might deliver the same benefits.

Another variable in society's ongoing uncontrolled experiment with
marijuana is its potency. THC -- short for
delta-9-tetrahydrocannabinol -- is the drug's most active ingredient,
producing a high and also relieving symptoms in some people. The NIDA
Marijuana Project, analyzing confiscated pot, found that the average
level of THC climbed steadily from seven-tenths of a percent in 1975,
with jumps to 2 percent in 1980 and 3 percent in 1982, to a record
8.5 percent in 2008. The rise was much more dramatic with imported
cannabis than the homegrown variety.

Despite these imponderables, Grant is hopeful that greater knowledge
will unlock more of marijuana's gifts and curb its dangers.

"I think we're learning quite a lot about cannabinoid receptors," he
said. "We do know that in the nervous system they're kind of like a
shock absorber; they seem to downregulate some signals from other systems.

"But so much more needs to be learned," he added. "We have plenty of
other medications that act on systems in ways we don't understand
very well, and yet they are legal. Antidepressants are a good example of that."

Klein said if the legalization trend continues, scientific research
should keep pace with it.

"I can understand why people want to see marijuana legalized, because
it does work for some people," he said. "But along with that comes a
responsibility to monitor what kinds of effects this greater access
is having on the population. We can't just make it more available and
turn our backs -- and then be surprised if something untoward starts
happening."

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MEDICAL MARIJUANA IN FLORIDA

Status

National medical marijuana activists' efforts in Florida are almost
nonexistent. An Orlando-based group, with no funding and a volunteer
base led by a stay-at-home mother, has in one year gained only 22,000
of the 687,000 signatures needed to put the issue before voters. Kim
Russell, founder of People United for Medical Marijuana, said her
group is "just getting started" and is also trying to lobby for a
medical marijuana bill in Tallahassee.

Strategy

Allen St. Pierre, executive director of the National Organization for
the Reform of Marijuana Laws, said it takes at least $5 million to
collect and verify signatures for a constitutional amendment. In
every state where the question of medical marijuana has been put to
voters, he said, the campaigns were backed by one of three wealthy
men: international investor George Soros, Progressive Insurance's
Peter Lewis and Phoenix University's John Sperling. To them, he said,
Florida looks like a bad bet, because the state is divided culturally
and has segregated media markets that make advertising costly.

Outlook

Polls find people in the South, including Florida, more skeptical
about the benefits of medical marijuana than Americans in the West
and North. There is no official support for legalizing pot in
Florida. Mary Lynn Mathre, president and co-founder of Patients Out
of Time, a Virginia-based organization, noted that the Florida
Medical Association issued a statement in 1997 supporting medical
marijuana research. But FMA media representative Erin VanSickle said
the group's position has since changed. "There were a couple of
different policies" on medical marijuana, she explained. "And they
were allowed to sunset, so now we have nothing."