MEDICAL-MARIJUANA ADVOCATES SEEKING SOCIETY'S APPROVAL

The liquid inside the test tube is neon green, the color of lime
Kool-Aid or the mad-scientist potions found only in comic books.
Perhaps it's fitting, then, that the contents come with a whiff of
danger. They are a mixture of marijuana and solvents, stirred
together in a furious swirl by a lab technician wearing protective
goggles and latex gloves.

Running the concoction through a $70,000 machine, the technician can
learn with scientific precision the plant's unique chemical makeup,
its potency, even its growing method.

The ultimate goal? Find out how good it is.

"We're not going to be taken seriously unless we have proof," said
Michael Lee, the owner of the lab and its adjacent medical-marijuana
dispensary, Cannabis Therapeutics.

This is the new science of pot, part of a fresh wave of study and
innovation among scientists and cannabis advocates all seeking to
solve a central dilemma: In Colorado and other states, first came the
approval of marijuana as medicine. Next comes the challenge of
proving its effectiveness.

The newest research leaves little doubt that marijuana -- or at least
its chemical components -- has promise in alleviating symptoms of
some ailments, while also making clear that the drug is not without
its drawbacks, some potentially serious.

What is less certain is whether Colorado's medical-marijuana system
of dispensaries and caregivers -- where commitment to scientific
rigor and compassionate patient care is largely voluntary -- can
maximize that treatment potential for the benefit of patients.

Some dispensaries keep detailed patient records and embrace
scientific testing in the hopes of providing patients with what works
best. But medical-marijuana users report other dispensaries seem
interested in just slinging snazzy weed, regardless of a patient's
needs or ailments. (One ad on Craigslist: "Licensed caregiver looking
to trade for Widespread Panic tickets.")

The mainstream medical community, meanwhile, questions whether any
system that uses a raw plant as medicine can be optimally effective.
Instead, conventional drug researchers see promise mostly in
harvesting marijuana's ingredients for more traditional medicines and
avoiding consumption methods like smoking that can hurt patients' health.

"If there is any future for marijuana as a medicine," a panel of
experts wrote in a landmark 1999 report for the National Academy of
Science's Institute of Medicine, "it lies in its isolated components."

Most marijuana advocates enthusiastically embrace a future in which
pot is as much an accepted medicine as penicillin. But that future
might not come without significant changes to the way medical
marijuana is handled. New medicines require new tests and government
approvals. Those lead to new regulations and new oversight. There is
a focus on standardization, sterility, precision, discipline.

If there were ever a world where marijuana was available behind the
counter at the corner pharmacy, the do-it-yourself independence of
Colorado's -- and many other states' -- medical-marijuana system
might not have a place. The bud could become obsolete, and
dispensaries -- both medically inclined and not -- could go extinct with it.

Indeed, not every marijuana supporter is watching the development of
cannabis-based pharmaceuticals enthusiastically.

"When they get through the FDA with their cannabis-based Click on
image to enlarge drugs, no legislature in the country will allow
doctors and patients access to whole, smoked marijuana," said Allen
St. Pierre, the executive director of the National Organization for
the Reform of Marijuana Laws, or NORML.

Medical Mystery

Medical marijuana hasn't always been a strictly on-your-own endeavor.

Historians have found references to the use of cannabis by healers in
China and India dating back to at least 2000 B.C. The Irish physician
William O'Shaughnessy wrote about the medical uses of cannabis in the
mid-1800s. Cannabis-based treatments were commonly prescribed in the
early 1900s in America before marijuana prohibition, which came about
in the 1930s because of concerns over the drug's psychoactive effects
and fears they could lead to criminal behavior.

What was missing, though, was an understanding of how marijuana
provided its touted medical benefits -- or, for that matter, even a
basic understanding of how marijuana gets people stoned.

"We knew marijuana has effects," said Bob Melamede, a biology
professor at the University of Colorado at Colorado Springs and a
prominent marijuana activist. "So the question was, 'How does it have them?' "

Answers arrived starting in the late 1980s with the discovery in the
body of something called the endocannabinoid system. The system acts
much like a traffic-control network, with receptors spread out across
the brain, the organs, the immune system and various other areas to
regulate functions as diverse as appetite, mood and pain. Using
chemicals produced in the body called cannabinoids as traffic cops,
the body turns on or off those receptors and controls the different functions.

Sending certain cannabinoids to one receptor and flipping it on, for
instance, stimulates appetite. Tripping another dampens the body's
inflammatory response.

Marijuana also contains cannabinoids that can fit into the
endocannabinoid system's receptors -- purely "pot luck," Melamede
cracks. Ingesting marijuana unleashes into the bloodstream swarms of
new cannabinoid molecules that quickly begin linking into the system
and flipping switches. This explains both the medical and
recreational effects of the drug -- which in many cases are one and the same.

By jiggering with the receptors that control appetite, for instance,
marijuana creates the much-joked-about munchies. But it is that same
effect that spurs the appetites and calms the stomachs of cancer and
AIDS patients. In the same way marijuana impairs the motor skills of
some users, it can also calm the painful muscle spasticity of
multiple sclerosis patients.

Highs and Lows

There is no scientific consensus that marijuana cures any disease or
ailment. But research generally suggests smoking marijuana has
pain-killing, muscle-calming, nausea-controlling and
appetite-boosting effects in many patients. That means studies have
shown marijuana can provide benefits to patients suffering from each
of the eight different medical conditions specified in the state's
medical-marijuana constitutional amendment.

Scientists, though, disagree to what extent marijuana is beneficial
and whether marijuana is more effective in those areas than existing
treatments. Medical-marijuana supporters, meanwhile, cite other
studies hinting at benefits in treating anxiety disorders,
post-traumatic stress disorder and many other conditions.

The effects also vary from user to user, and using marijuana is not
without its risks. Studies have shown smoking marijuana may be more
harmful to the lungs than smoking cigarettes. Other studies suggest
marijuana could lead to increased anxiety or more severe
mental-health problems in some people and dependence in others.
Marijuana is the most commonly cited drug for people seeking
treatment for illicit drug abuse, according to the U.S. Substance
Abuse and Mental Health Services Administration.

Mostly, though, mainstream medical-marijuana studies and
researchreviews conclude that more thorough clinical trials of the
drug are needed. Those follow-up studies are made difficult by
federal drug-control laws, which place tight restrictions on
marijuana research.

The proliferation of state medical-marijuana programs has been of
little use to researchers, said Cecilia Hillard, a neuroscience
professor at the Medical College of Wisconsin and a past president of
the International Cannabinoid Research Society. Participants in those
programs are self-selected, she said. That means those patients are
pre-disposed to thinking marijuana will help, further muddying the
scientific analysis of raw marijuana's benefits and drawbacks.

"It's hard to say how much people are really using it medicinally
versus recreationally," Hillard said. "Right now we're sort of to a
point where the claims of medical benefit are so numerous and so
over-the-top that you tend to get into the realm of, 'Well, I just
don't believe any of this.' People are saying it's good for everything."

A handful of recent clinical trials -- the first clinical trials of
smoked marijuana in this country in 20 years -- have provided some
clarity. After being tasked by the California state legislature, the
University of California at San Diego's Center for Medicinal Cannabis
Research sponsored about a half-dozen placebo-controlled trials to
assess whether marijuana is effective as a painkiller for HIV and
multiple sclerosis patients and for people suffering from nerve damage.

Across the board, the trials found some promise in marijuana as a
treatment option.

"I was a little bit surprised, to tell the truth," said Igor Grant,
the center's director. "I somewhat expected that what we would get is
a mixed result . . . which would not be so unusual. But the fact that
all of them came up with a consistent result makes me feel a little
more comfortable in saying we could have something here."

That does not mean, however, that Grant is ready to proclaim
marijuana as a miracle treatment. For starters, patients in the
trials generally continued on the drugs they were already taking for
their conditions and used marijuana to supplement. Second, Grant
said, smoking marijuana is just too impractical a delivery method for
medicine. Among the questions: How do you control the dosage?

"Would you prescribe smoking cannabis cigarettes in a hospital room
where oxygen tanks may be present?" Grant asked. "The great
likelihood is that we need alternative systems."

And that is exactly where marijuana's pharmaceutical gold rush is taking place.

Separating Help From High

Sitting at lunch one day recently in a restaurant near his UCCS
office, Melamede, the biology professor, reaches into his jeans
pocket and pulls out two small vials containing inky green liquid.
They are marijuana extracts, he explains, formulas carefully measured
for potency and chemical makeup that can be taken under the tongue in
a predictable dosage. He also has ideas for marijuana skin patches,
tongue strips and lozenges, all part of a new publicly traded
pharmaceutical venture he has embarked on called Cannabis Science.

"The key thing is," he said, "we're addressing the government's
concern that smoked marijuana is not medicine."

Cannabis Science recently hired a company to help it negotiate the
Food and Drug Administration approval process, and Melamede said he
is hopeful it won't be long before the company can begin clinical
trials targeting veterans with post-traumatic stress disorder and
chronic pain patients.

But Melamede knows he is already behind in the race. GW
Pharmaceuticals, a British firm, is currently preparing for its final
clinical trials in the United States on a drug called Sativex, a
marijuana-derived mouth spray the company intends as a treatment for
cancer pain. The drug has already won approval in Canada and Great
Britain and is in the last stages of approval in Spain.

What makes Sativex unique among current pharmaceuticals is that it is
a blend of natural cannabinoids made directly from marijuana plants
- -- grown in southern England -- rather than synthetic re-creations of
marijuana components, like drugs such as Marinol.

GW believes such an approach will yield better medicine, and it is
already experimenting with other cannabinoid combinations for new drugs.

"There are more than 60 cannabinoids in the cannabis plant, so we
believe that leaves plenty of scope for future development," GW
spokesman Mark Rogerson wrote in an e-mail.

Most exciting to those looking to establish marijuana's potential
benefits as medicine in a more socially accepted form is a
cannabinoid called cannabidiol, or CBD. A batch of new studies
suggest it may have medical effects like THC -- the chemical in
marijuana that gets a user stoned. But it eliminates the
psychoactivity produced by THC. In other words, it's medical pot that
won't get you high.

Colorado dispensaries have begun to stock marijuana strains high in
CBD. But to tout a strain as being CBD-rich, it helps inspire
consumer confidence to prove that it is, which is where laboratory
testing comes in. Using pricey machines called high-performance
liquid chromatography systems, medical-marijuana labs can detail the
percentages of THC, CBD and a handful of other cannabinoids in the
plant. The lab work is unchecked by the government and is performed
only by labs either connected to or hired by dispensaries.

A number of dispensaries across the state now routinely place little
cards detailing the test results next to each strain in their display
cases. Patients can use the cards to pick marijuana suited to their
need based on the numbers and not the strain names, which aren't
always descriptive of a strain's effects.

"We hope to take the mystery out of the names and put in more
science," said Frank Quattrone, the owner of Pure Medical Dispensary
in Denver. ". . . The names, hopefully, will become irrelevant."

Dispensaries have also used the laboratory analysis as a guide in
developing more potent product. Cannabis Therapeutics in Colorado
Springs has developed a hash oil -- essentially concentrated
marijuana -- that it touts as 86 percent THC. (Even the most
knock-out marijuana buds are usually no more than 20 percent THC.)

Andreas Rivera, Cannabis Therapeutics' manager, says the oil will
only be sold to terminally ill patients as a form of palliative care.

"It's really about pain management instead of getting people super
stoned," he said.

But the availability -- and marketability -- of such products raises
a question: Are patients actually using the analyses to find the best
medicine or the best high?

Inside Cannabis Therapeutics, it is clear most patients currently see
only limited value in the new data. Some ask about the numbers, but
their eyes quickly glaze over during the explanation. Others skip the
numbers entirely, instead choosing by past experience or the much
cruder ratio of how much "upper" versus "downer" the strain contains.

Most patients rely to some extent on the advice of the woman working
behind the counter, Julie Anderson.

"I usually ask Julie what the best she's got is," said patient
Frederick Ross, who suffers from such severe appetite loss because of
various medical conditions that he eats only once a day. "I don't
play the numbers."

But some patients have taken an interest in the new data. One woman
with kinky, waist-length, brown hair crouched in front of the counter
to study the numbers for several minutes before making her selection.
She said she has been writing down the THC and CBD ratios of the
strains she's tried and has used the data to guide her decisions.

"I'm trying to apply some analysis to it and some logic based on the
information I have," explained the woman, who asked that her name not
be used because she didn't want her co-workers to know she is a
medical-marijuana patient. "Hopefully I can make a more-educated decision."

Whatever the efforts by dispensaries to put more science behind their
products, though, they're likely to be met with a sniff from the
pharmaceutical industry, which believes most people will never accept
taking medicine by smoking a raw plant.

"The current system of distribution may actually prevent cannabis
from ever being accepted as a mainstream medicine by most patients
and physicians," GW's Rogerson said.

People in the medical-marijuana business naturally bristle at such
talk. But among some there is a sense that wider acceptability of
marijuana by the medical world might actually restrict marijuana access.

State medical-marijuana programs, NORML's St. Pierre explained,
function as relative oases for cannabis access -- bypassing a whole
set of federal rules because the federal government simply refuses to
participate. Right now, marijuana is legally a Schedule I controlled
substance because the federal government sees no accepted medical use
for it and considers it to have a high potential for abuse. That
classification means doctors can't prescribe it and pharmacists can't
distribute it.

If marijuana were to be placed in a less-restrictive classification
- -- as a petition currently pending with the Drug Enforcement
Administration requests -- doctors potentially would be able to
prescribe it. That ability, though, would bring with it Food and Drug
Administration oversight, production controls, inventory caps,
distribution limits, security rules and more. Plus, with a federally
blessed system to get patients cannabis in the same way they get
cholesterol drugs, why would most state governments continue with
their jury-rigged medical-marijuana systems?

"We see this as a boxed canyon," St. Pierre said.

Limitless Learning

Back at Cannabis Therapeutics' lab, John Kopta -- a Colorado State
University biochemistry grad who runs the facility -- is more
optimistic. Only a few other labs in the country, mostly connected to
the medical-marijuana industry, are doing what his does. The more
study they do, the more proof they have. The more proof they have,
the more they can lead the way forward.

"There's dozens of different cannabinoids in the plant, and we know
of 10 of them and what they do," he said. "It's really limitless."