Pubdate: Sun, 4 Jul 2010
Source: Denver Post (CO)
Copyright: 2010 The Denver Post Corp
Author: John Ingold, The Denver Post
Bookmark: (Cannabis - Medicinal - U.S.)


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."
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