No, Cheech and Chong aren't on the payroll. Neither is the Weed Man. They don't have free samples, or the munchies. And their office Christmas party wasn't any wilder than yours was.

But as a small pharmaceutical firm working on a medicinal product derived from the same plant that's, um, high on the radar for recreational purposes, some ribbing is to be expected.

Luckily they take it all in stride at Toronto-based Cannasat Therapeutics Inc., one of a handful of companies in the world that is researching and developing medicines derived from cannabis plants ( yes, that would be marijuana ).

Their aim is something a lot more serious: to help people suffering with chronic and neuropathic pain, depression, anxiety and movement disorders using all the known benefits of cannabis - including being a pain reliever, a relaxant, an anti-nauseant and an appetite stimulant - minus the social stigma of smoking pot.

On top of that, their first product in testing, CAT-310, takes away the so-called "buzz" of marijuana that makes some terminally and chronically ill patients, particularly the elderly, uncomfortable and anxious. This medicine is aimed directly at the $4 billion neuropathic pain market that is mainly serviced by various opiates, anti-convulsants and anti-depressants.

Cannasat's pursuit is all perfectly legal and has the backing of Health Canada, including a narcotics licence, "and you have to be a pure-bred pharmaceutical company to get one," notes chief executive David Hill.

His mission since Cannasat was launched in 2004 is to educate investors about the benefits of what he refers to more scientifically as "cannabinoids," the naturally occuring molecules unique to the cannabis plant. The best known is THC (tetrahydrocannabinol).

The idea is to mimic smoked cannabis through the invention of a new drug delivery technology that can be absorbed on the tongue, like a thin wafer. It doesn't get digested by the stomach and processed by the liver before reaching the brain, so it's similar to inhaling cannabis.

There are other products on the market using THC, including capsules and an oral spray, but anything that lands in the stomach and is processed by the liver increases the high, he explains.

"What we're trying to do is we've created a sublingual tablet so it goes into the mouth, into the bloodstream and then into the brain. What's compelling is when you take oral THC, it's five times more psycho-active. When it goes through your stomach and metabolizes, it's getting you high.

"So it's losing its efficacy and it's making you more stoned. So we're trying to take clinically proven molecules and reducing the high," Hill says.

One of the pluses is that THC is known to be an effective treatment for neuropathic pain and nausea.

"Most people who are sick don't want to get high. And what doctors are reluctant to do is prescribe medications that get you high," such as opiates, which can also be toxic, make you nauseas and constipated.

"Cannabinoids are safe. They're virtually non-toxic. We all remember from high school that if we drank too much we got sick. But if you smoke too much pot the worst thing that would happen to you is you fell asleep. And when you woke up the next day you might have been a tad groggy, but really there's no hangover.

"We know from recreational data that when some people take ( smoke ) too much THC it can cause paranoia, it can cause anxiety. Some people love it to death. They think it's just wonderful. But for some people it causes anxiety," says Hill.

Opiates such as Oxycontin and codeine can help with pain relief but they've been proven to be highly addictive. THC is much less so, he says.

"The biggest problem with oral dosage forms of THC today, the spray and the capsule, is that THC is a very thick, oily substance.

"Our solution is we have a nano-encapsulation technology. It takes that oily substance and turns it into a powder, so that powder will now dissolve in the saliva," and you don't have to swallow it, he explains.

"We know this works. If we can create a more elegant delivery system, I think we have a very marketable pharmaceutical product," Hill says.

One person who is excited about the medicine's potential is Sara Lee Irwin, Cannasat's director of public relations. When she was 32 years old she was diagnosed with cancer in her pelvis and hip. Today at 50, she walks with a cane and still suffers from chronic pain.

She's taken every powerful painkiller out there from Percodan to Oxycontin but found she couldn't function normally in her daily life because of the high, the constipation and the lack of appetite. She's taken THC in oral capsules but she's never found it as effective as smoking herbal cannabis.

Because of her condition, Irwin is one of the 2,000 people in Canada legally allowed to purchase and use medical marijuana, which she smokes three or four times daily to ease her suffering.

"I've switched over completely. It moves the pain off-centre and I have a ravenous appetite," she notes.

When it comes to her company's mission: "I feel really good about what we're doing, and I have a great interest in this," Irwin adds.

Recently Cannasat reached a milestone they hope will get them closer to their goal of bringing a safe and effective product to market.

Earlier this month Cannasat successfully completed Phase I clinical trials, the first key study in humans that now provides them with important safety and medical data to launch them on to further product development.

"It's an important first step for us. It keeps us on track to move CAT-310 to Phase II testing by the end of 2008," he says.

It's at that point that the big pharmaceutical companies take notice and could sign on as a partner to market and distribute the product. They're already in preliminary talks with some, he says. They estimate revenue potential of $500 million-plus.

"We're not doing this to be a little, wee company. We see huge potential here," Hill says.

Cannasat went public last year on the TSX Venture Exchange and continues to trade at or around its 52-week low of 17 % a share. Its market captialization is about $14 million.

Companies getting into Phase II of clinical trials, as they will be next fall, are trading north of $100 million in market cap, he says.

"We have great potential to be a big company with institutional money and move the research along further," Hill notes, adding their next products will be aimed at treating mood disorders such as anxiety and depression, and with localized pain.

But what about the public perception about pot?

"Now that we've established ourselves as a pharmaceutical company, I don't see that stigma. It certainly hasn't held us back in Canada. We've had a lot of support from Health Canada," offers Hill.

"I think the only stigma we have is that the average person, when they hear about it, their first reaction is cannabis is somehow a back alley drug. And I'm trying to show that (opiates) are a back alley drug too.

"I'm not some closet pot smoker or anything. I got into this because the company approached me with a business opportunity and I wanted to do something that I could be really passionate about.

"I realized there's an enormous business opportunity here that could really help people."

Copyright: 2007 Toronto Star

Source: TheStar.com

FDA "ADVISORY" AND MANUFACTURERS "PATIENT INFORMATION" STATEMENT ON METHADONE FOR PAIN - FAR TOO LITTLE, FAR TOO LATE

On Nov. 27, 2006, FDA issued an "advisory" on methadone for the management of pain. It and the associated new "patient information" issued by Roxane Labs actually divert attention from the only major change that has recently been introduced: a marked reduction in "usual" starting methadone dose from a maximum of 80mg to a maximum of 30 mg per day.

Neither the FDA Advisory nor the manufacturer's information sheet makes any reference to any specific dosages - let alone is there mention of the dramatic reduction in what is considered to be an appropriate "usual" starting dose. It's hard to imagine why, since this flurry of activity is clearly in response to the recognition that 80 mg on day one is potentially lethal. One would imagine banner headlines on both documents proclaiming 30 MG methadone IN FIRST 24 HOURS TOP OF THE RANGE FOR INITIATING TREATMENT FOR PAIN; HIGHER DOSES CAN HAVE FATAL OUTCOME. Sure, one would want to leave flexibility to the individual practitioner - but the generalization of high, potentially fatal, risk should have been highlighted and extreme caution urged before exceeding the "usual" range. Instead, as noted, dosages were not even mentioned! What did receive great attention, as reflected in the very title of the FDA advisory, are references to allegedly life-threatening "heart beat" irregularities, though we have been unable to identify a single report in the professional literature of any death attributed to methadone-induced cardiac effects.

So where does one find the dramatic new methadone dosage references? Only on page 15 of a 17-page, very fine print, comprehensive, description of methadone (Dolophine, to be exact). There, under the heading "initiation of therapy in opioid non-tolerant patients, is written: "...the usual oral methadone starting dose is 2.5 mg to 10 mg every 8-12 hours slowly titrated to effect." Until now, the same section read : 2.5-10 mg every THREE TO FOUR HOURS. Thus, the top of the range for initial management has been reduced from 80 mg to 30 mg but no hint of this very substantial reduction is alluded to by either FDA or Roxane.

Clearly, the "advisory" and "patient information" notices are far too little in not spelling out up front precisely what new message must be heeded to protect patients. The notices are also far too late - certainly, too late for some of those patients who may have been prescribed the previously noted "usual" methadone doses, and/or who relied on the FDA-approved "package inserts" that spelled out the same total day one range of 15-80 mg, and who may have suffered an overdose as a result. Note that a 2003 study (Ballesteros et al, JAMA, July 2, 2003) of deaths "due to methadone" in North Carolina, reported by CDC, found that of almost 100 patients for whom information was available "75% had been prescribed methadone by a physician." One can only speculate whether at least some of these deaths might have been avoided had the "usual" methadone dosages specified by FDA and the manufacturer been consistent with what has been known for decades. Indeed, FDA itself puts a 30mg day one limit on starting doses of methadone for opioid-dependent (and thus opioid tolerant!) individuals beginning maintenance treatment (see, for example, the US Department of Health and Human Services Treatment Improvement Protocol TIP 43," 2005, p. 67; and also the 1999 Federal Register, July 12, 1999, vol. 64, number 140, p 398401). The evidence regarding initial methadone dosages that are least likely to cause serious adverse effects is massive, consistent and worldwide; it was embodied years ago in the clear and concise Province of Ontario methadone maintenance guidelines: "START LOW, GO SLOW".