SMOKING OUT POT'S MEDICAL POTENTIAL

A Landmark Study Funded By The State Is Researching The Therapeutic
Value Of Marijuana.

SAN FRANCISCO -- Robert has taken a lot of prescription drugs over the
past 15 years.

One made him vomit without warning. Another tasted like motor oil. One
drove his cholesterol to heart-attack levels. Still another caused a
hot, tingling pain in his hands and feet.

Late last month, Robert checked into San Francisco General Hospital to
test a drug to quiet the nerve pain. This one left him temporarily
giggling and bewildered.

As someone who's been sick from HIV for most of his adult life, Robert
found the side effects of this test drug gentle. "It is really mild
compared to everything else," he said.

Another important difference between the test drug and other
medications he's taken is that the test drug is illegal: It's marijuana.

Under the circumstances, Robert is breaking ground, not breaking the
law. He is the first participant in the first study to be encouraged
and paid for by the state of California on the therapeutic effects of
Cannabis sativa -- better known as pot.

The study, led by Dr. Donald Abrams at the University of California,
San Francisco, is under the aegis of the Center for Medicinal Cannabis
Research. Unique in the country, the agency was established by a 1999
state law that provides $3 million a year for three years to research
marijuana's potential as medicine.

Three years earlier, in 1996, voters passed Proposition 215, allowing
ill people to smoke marijuana under a physician's care. Research
supported by the center is meant to help guide doctors on the
appropriate uses and doses for specific ailments.

Anecdotes abound on the therapeutic effects of cannabis, but most
credible studies have been on laboratory animals. Further, past
research largely focused on marijuana's health consequences, not
potential benefits.

With California in the vanguard, that's changing. Canada last year
legalized the use of cannabis as medicine and is funding research on
its healthful effects. Great Britain is considering allowing medical
marijuana use, and supporting research.

Social acceptance of marijuana as medicine is so new and tenuous that
people involved in the research are cautious about their
participation.

Robert, for example, asked to withhold his last name in print. Apart
from the UCSF study, the 39-year-old has a Proposition 215 permit to
smoke marijuana for his nerve pain, which he's done at a cannabis club
on weekends.

Despite the fact that his smoking is legal, and that he lives in
liberal San Francisco, Robert said using pot therapeutically is "kind
of a closet-y thing."

"It's a little tricky," he said, mindful of his Catholic upbringing.
"I don't even know how I'm going to tell my parents."

Hector Vizoso, a nurse experienced in clinical trials, hesitated
before accepting a job at UCSF as study coordinator.

"Because I'd be dispensing marijuana, would I be considered a dealer?"
he wondered.

His worries were calmed by Abrams, a 51-year-old physician, and staff
members at San Francisco General, who knew what a medical cannabis
study entails.

In 1998, they undertook the first-ever study to be done on the use of
smoked marijuana in people with HIV. The project followed a tenacious
fight by Abrams for approval from the National Institute on Drug
Abuse, keeper of the country's only legal source of research marijuana.

Twice, his study proposals were rejected. On the third attempt, Abrams
rephrased the research question, playing up the drug's possible
faults: Might marijuana interfere with the medications used to
counteract AIDS?

Abrams won nearly $1 million in funding and a supply of marijuana to
answer the question.

He found that marijuana didn't worsen AIDS virus levels. In fact, it
helped patients eat more and gain weight.

Abrams has cared for people with AIDS since before the disease had a
name. He knew that some smoked marijuana on their own to quell nausea
and stimulate their appetites.

"We feel indebted and obligated to our patients to determine if it's
safe and if it has some effect," he said.

Abrams' new, three-year, $956,000 state-funded study focuses on the
potential of cannabis to relieve AIDS-related peripheral nerve pain --
a debilitating pain in hands and feet that may occur as a result of
the disease itself, or as a side effect of drugs taken for AIDS.

One requirement of study participants is that they be experienced
marijuana smokers.

"We want to know people know how to inhale -- and know ... what it's
like to be stoned, so they don't freak out and sue us," Abrams said.

The study is starting as a pilot with 16 volunteers, most of whom
still are being lined up. Each will stay in the hospital for nine
days, smoking marijuana on seven of those days. Those who stick with
the study for the full duration -- a commitment of about a month or so
per person, including keeping a pain diary for a week before and a
week after the hospital stay -- are reimbursed $600 apiece.

If all goes well with the pilot, a bigger study involving up to 100
subjects will follow. That study will use placebos -- marijuana
cigarettes missing the chief active ingredient, THC -- and be
double-blinded, meaning neither subjects nor researchers in contact
with the subjects will know who gets the placebo and who gets the real
thing.

Robert was the first subject. He checked into the hospital March 27,
bringing a stationary bicycle, music, books, props for meditating and
a cooperative attitude.

He was careful to smoke each marijuana cigarette exactly as directed:
Inhale five seconds, hold 10 seconds, exhale, and pause for 45
seconds. Repeat.

The first time, Robert wasn't sure he could smoke the whole thing.
Three inhalations of the cigarettes he gets at the cannabis clubs are
plenty. But the government-issued cigarettes are weaker. Robert kept
smoking.

"One of the reasons I'm in the study, I want to be part of showing
that it's effective," he said. "So I want to do my part."

With AIDS, Robert has lived a cat's life, dodging death time and again
with the help of new drugs. But the drugs have caused grief, too. One
medicine he began in January 2001 triggered the pain in his hands and
feet.

His doctor lowered the dose, and Robert's hands settled into a quiet
numbness, but his feet are still prone to a hot, achy soreness that
feels like he's walking on bare bones.

Even taking two different painkillers, he rates the pain five or
higher on a scale of one to 10.

In the hospital, the marijuana knocked it to zero for almost the
entire time between doses.

To qualify for the study, Robert had to abstain from marijuana for 30
days beforehand. Normally, he smokes once a week, which isn't enough
to be pain-free, but provides some relief.

"There's always a balance between wanting to manage your pain and
wanting to be lucid, wanting to function," he said.

Smoking three times a day most days in the hospital -- at 8 a.m., 2
p.m. and 8 p.m. -- Robert was fuzzy for about 90 minutes after each
dose.

"There are times when I feel pretty high, like wooo!" he said, midway
through his stay. "The morning thing is the hardest. You're just
getting up, you're already spacey. ...

"So I wake up, and I try to do, like, all my showering, making the bed
and opening the window because I know after that (cigarette),
nothing's going to get done." He flashed an impish smile.

Usually, he took the marijuana alone in his fifth-floor room, a fan
venting the smoke to the outdoors, a nurse watching through a window
from the hallway.

The distinctive, pungently sweet odor of marijuana can make for an
awkward situation in a hospital. Once, Abrams visited as Robert took a
dose. The doctor stepped out five minutes later looking abashed.

"I've got to go see patients, and I smell like smoke!" he
gasped.

THC is available in a pill, but it doesn't seem to work as well. Dr.
Mark Wallace, a pain specialist at UC San Diego who plans to study the
painkilling effects of smoked marijuana in healthy adults, said
inhaled cannabis goes right to the bloodstream, almost as directly as
an injection.

He said some pharmaceutical companies are trying to develop inhalers
to deliver marijuana. Robert would just as soon take the drug some
other way. He found the smoke bothersome.

Grown in Mississippi, the government marijuana arrives freeze-dried
and must be carefully humidified before use. At UCSF, it's kept in a
padlocked refrigerator in the pharmacy. A nurse weighs each cigarette
before it's smoked, then collects the ashes and butt for return to the
federal government.

On Friday, Robert's first day home after smoking 19 cannabis
cigarettes in seven days, he reported feeling a mild sinus irritation
from the smoke. Otherwise, he said, he felt good.

In coming weeks, dozens of other subjects will enroll in cannabis
studies in the state. The Center for Medicinal Cannabis, which is
managed by the University of California, has selected 11 for funding
so far; eight have the federal go-ahead.

Center director Dr. Igor Grant said that while most studies will run
two or three years, results might emerge sooner. "The studies are
designed to develop some answer," he said. "If there's a very, very
clear effect, we may know sooner."

The existence of the center has advanced the field already, unleashing
pent-up interest. Many of the scientists with pending cannabis
projects long have wanted to study the plant but were daunted by the
legal tangles.

"Oh gosh, the regulatory minutiae you'd have to go through!" said
Wallace, the pain specialist.

Marijuana is a Schedule I drug, meaning the government recognizes no
medical benefit. Research proposals involving marijuana are
scrutinized by four federal agencies: the Department of Health and
Human Services, the Food and Drug Administration, the Drug Enforcement
Agency, and the National Institute on Drug Abuse.

State Sen. John Vasconcellos, D-Santa Clara, sponsor of the
legislation that created the state cannabis center, cheered its
progress last week. "They've worked heroically and systematically and
credibly," he said.

Abrams' AIDS neuropathy study was one of the first to be approved by
the center, back in the fall of 2000. Abrams acknowledged it's been a
long haul, but he's not looking back.

"I hope this is ushering in a new era in marijuana studies," he said.