THERAPEUTIC EFFECTS OF CANNABIS SATIVA STUDIED

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' 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.

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."

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.