|16 Apr 2004 @ 00:01, by ming|
From Sounding Circle: Nature's Oldest Drug Is Now the World's Newest Pharmaceutical
Pubdate: Thu, 9 Oct 2003 Source: The North Bay Bohemian(CA) Copyright: 2003 Metro Publishing Inc.
Author: Mari Kane GW Pharmaceuticals
Relief in Pill Form
NATURE'S OLDEST DRUG IS NOW THE WORLD'S NEWEST PHARMACEUTICAL
Beckie Nikkel does not consider herself a "sufferer" of multiple sclerosis because she has learned to deal with the disease by taking control of the medicine she takes. Five years ago, the 50-year-old Santa Rosa grandmother was taking a dozen different meds, some to counteract the side effects of others, and her next step would have been to use a baclofen pump to stop the muscle spasms, which would have rendered her legs useless. That's when she turned to cannabis and became active with the Sonoma Alliance for Medical Marijuana. In late September, she joined a convocation of activist organizations in Washington, D.C., to lobby congress and the National Multiple Sclerosis Society about cannabis.
"I used to use a vaporizer, but now I do more ingesting of cannabis nectars and candy," she says, referring to THC-laden pops distributed privately. "Those suckers work wonders, but I would love to have other natural options, especially if they were covered by insurance."
Though the federal government's stance against all things cannabis continues to thwart the efforts of Nikkel and many others, research in Europe--where the climate is remarkably milder when it comes to marijuana--is pushing forward.
At the head of the new wave, British-based GW Pharmaceuticals stands out. Under government license and using plant strains developed by HortaPharm of Amsterdam (owned by expatriate Americans David Watson and Robert Clark), the company grows high-grade, finely tuned marijuana at a secret location in the south of England. With that crop, GW has isolated beneficial cannabinoids--the active ingredients of cannabis--and created a sublingual (under the tongue) spray for the treatment of multiple sclerosis symptoms.
Of course, Beckie Nikkel currently has no chance of getting her hands on the medicine legally. If she did, according to GW's three years of clinical trials, she could find relief from her neuropathic pain and muscle spasms, and she could get a more peaceful sleep. Her appetite would increase. If Betty Nikkel could get GW's medicine (a blend of two cannabinoids brand-named Sativex) through her insurance company, she could feel a lot better.
GW Pharmaceuticals hopes to gain approval from the British government for Sativex by the end of this year. In May, the company signed a lucrative marketing agreement with the German pharmaceutical giant Bayer to help them launch the product in Europe in 2004. So now, the world's first natural cannabis pharmaceutical maker has nowhere to go but up, yet the inevitable question remains, how high?
Cannabis may well be one of the world's greatest natural remedies. Human beings have long used cannabis to relieve symptoms of everything from nausea to pain. In fact, the human relationship to cannabis is so tightly ingrained in our physiology that special receptors have evolved in our brains to link to the chemical components of the plant.
Cannabis sativa, what we now know as "marijuana," officially entered the Western pharmacopoeia over one and a half centuries ago, during Victorian times, when cannabis medicines were administered in the form of tinctures. Queen Victoria is perhaps the most celebrated consumer of early cannabis tonics.
Having a record of no known cases of fatal overdose in the history of the world, the safety of marijuana is miles ahead of even aspirin. The biggest side effects of cannabis are euphoria and possibly paranoia. With its reputation of being one of the least toxic therapeutic substances on earth, the market potential for quality-assured, health-insured cannabis drugs has not gone unnoticed by pharmaceutical companies.
Marijuana is nothing without cannabinoids. These molecules of medicament are found in the millions of tiny, resinous pistils that shoot from the cannabis leaves. The mightiest cannabinoid of all is delta-9 tetrahydrocannabinol (THC), from which the famed euphoric effect is attributed. But cannabis therapy does not end with THC. All kinds of analgesic, antispasmodic, anticonvulsant, antitremor, antipsychotic, anti-inflammatory, anti-emetic, and appetite-stimulant benefits are derived from other, lesser known cannabinoids, such as cannabinadiol (CBD). GW Pharmaceuticals has combined THC and CBD to make Sativex.
"Our intention, once we have a product license application in the U.K., is to use the mutual recognition procedure to obtain approvals in other European Union member states, probably during 2004," says GW's spokesperson Mark Rogerson. "We will also be seeking to market the product in Commonwealth countries such as Australia, New Zealand, and Canada. The U.S. market is a longer-term objective."
Rogerson is not kidding when he says America is a market they'll have to wait for. The Bush administration and the Supreme Court remain in denial of marijuana's medical benefits, and the new DEA administrator Karen Tandy has indicated that raids against California compassion clubs will continue.
By contrast, Europe and Canada have made great strides toward marijuana decriminalization, efforts which often incur the wrath of the U.S. government. Once Sativex is approved in Europe, intrepid American patients who attempt to smuggle it home will have to answer to the customs man, just as if the drug were hashish.
"If [Sativex] has not been approved by the FDA, we would not let it enter the country," said U.S. Customs Service spokesperson Michael Fleming. "If it is prohibited entry, there could be civil and possible criminal penalties attached."
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While the FDA refuses to comment on drugs not currently under review, it is expected that no matter what the political climate, any cannabis-related drug would have to undergo the same three-stage approval process as all others.
Stage one of the process involves preclinical research on animals and submission of the Investigational New Drug Application to the FDA. Stage two includes clinical research on humans in five phases.
The catch with conducting clinical trials using natural whole cannabis or its extracts is receiving the special permission to handle a substance that currently tops schedule one of the DEA's controlled substances list--more or less, the America's most wanted of drugs. Permission often includes the requirement to use low-quality, government-issued pot grown on a federal farm in Mississippi.
Finally, stage three involves FDA review and, hopefully, approval of the New Drug Application. Only after many years and millions of dollars later is the new drug marketed. Meanwhile, patients continue to smoke their medicine.
GW Pharmaceuticals has not revealed the cost of Sativex to patients or their insurance providers, leaving that to Bayer, but a full-time regimen is expected to be expensive, making some wonder if this is not snake oil in a hemp package.
Some of the most vociferous criticism of Sativex comes from within the medical marijuana movement itself. Dr. Lester Grinspoon, emeritus professor of psychiatry at Harvard Medical Center and author of Marihuana: The Forbidden Medicine and Marihuana Reconsidered, says that smoked pot is still less expensive, more convenient, and more reactive than extracts, so why buy Sativex?
"I imagine [Sativex] will be as efficacious as smoked marijuana, but it's not as good because you can't titrate it," he maintains. Titration involves incrementally increasing the dosage to achieve the desired relief. "Fifteen to 45 minutes is too long to titrate. You want immediate effects and you don't want to go too far, but the longer the effect takes to come on, the more difficult it is to titrate it."
Grinspoon is convinced that, despite the widespread fear of smoke inhalation, smoking is still the best way to titrate cannabis, because the cannabinoids go from the lungs to the heart and directly into the brain all within a minute.
According to Rogerson, regular users of Sativex have figured out how many squirts they need. "Patients in the clinical trials reported that it was not difficult over a few days to establish a dosage regime," he says. "The fact that it only takes a few minutes to determine symptom relief allows for effective titration."
As far as where the market lies for a competitor against street pot, Rogerson says the demographics include any patients seeking a medicine approved by the regulatory authorities on the grounds of quality, safety, and efficacy. "We believe that many patients will wish to use a medicine that is legally prescribed, does not require smoking, is of guaranteed quality, and is available from their doctor."
While Sativex is the first drug made with natural cannabis extract, it is by no means the first attempt to pharmaceuticalize pot. The synthetic THC drug, dronabinol, brand name Marinol, was approved by the government in 1986, essentially to solve the "marijuana problem" by pharmaceuticalizing it. However, Marinol capsules require one and a half to two hours to take effect, so titration is key.
But, Grinspoon warns, if you take too much, you'll get very high; if you take too little, you get no relief after all that waiting. "I have never had a patient who has used both marijuana and Marinol who doesn't prefer marijuana," Grinspoon declares. The onset time of GW's extract spray is quicker than the oral delivery of Marinol, but it is still slower than smoking.
Around the world, more pharmaceuticals are turning on to marijuana, putting more cannabinoid drugs into the pipeline. The Israeli company Pharmos has created a synthetic dextrocannabinoid product called dexanabinol for the treatment of head trauma and stroke, and recently began phase three trials for FDA approval in the United States, the first of its kind in this country.
Synthetic cannabinoids are analogues of cannabis, with a similar chemical structure, built in the lab and not derived from natural cannabis. Since they are not handling a controlled substance, producers of synthetic cannabinoid drugs are not legally hamstrung like GW pharmaceuticals is.
Previous trials have shown that dexanabinol prevents ischemia, which is a reduction of blood flow to the brain that can cause cell death. A single injection of dexanabinol given within six-hours after a traumatic brain injury protects against neurological deterioration. And, since head injury victims don't need more of a buzz, dexanabinol is designed not bind to the brain's receptors that stimulate the psychotropic effects.
The use of cannabinoids to treat head injury is supported by the famously ignored 1999 report by the National Academy of Sciences' Institute of Medicine which concluded that marijuana's neuroprotective qualities are the "most prominent" of its potential therapeutic applications. If all goes according to the company's plan, dexanabinol will become the world's first therapeutic treatment for traumatic brain injuries, greeted by a global market valued at over $1 billion.
For investors, this is an exciting time to make money on the worlds oldest cultivated plant. GW's stock price has doubled in the past two years. Irv Rosenfeld of Lauderhill, Fla., is perhaps the only American broker selling GW and Pharmos stock, and he believes that as awareness and demand rise, so will the stock price.
"GW stock will get a shot in the arm when Sativex is approved in England, and every time another country approves it, it will get another shot," Rosenfeld predicts.
Rosenfeld is also enthusiastic about Pharmos and expects its stock to do well once phase three studies are presented to the FDA one to two years from now, and once the company finds a strategic marketing partner.
"The difference is that Pharmos has just one cannabinoid they're working with, where GW is working with more than one," Rosenfeld notes. "But Pharmos is going to be able to use dexanabinol in other areas of treatment, which will also be very beneficial to their stock."
Rosenfeld is a singular broker of cannabis pharmaceutical stock, claiming to have 32 years of due diligence in the area. As the longest surviving member of the now-closed federal Compassionate Investigational New Drug program, Rosenfeld has been smoking 10 to 12 cannabis cigarettes per day for over 30 years to repress his recurrent bone tumors. For the past 20 of these years, his supply has come from Uncle Sam, the same entity that refuses to admit that pot has medical value.
"All these years they've been telling me marijuana is not medicinal. It's nice to finally be vindicated on that point," Rosenfeld says.
While there may be disagreement over the superiority of smoked marijuana to extracts, one thing most observers agree on is that the commercial success of any cannabis drugs is certain to affect U.S. drug policy. After all, how long can anyone deny marijuana's medical efficacy after publicly owned pharmaceutical companies start selling prescription extracts of the stuff?
"The success of any cannabinoid medicine will depend on how diligently prohibition is pursued," Grinspoon suggests. "If there were no prohibition, who would take Sativex? Only people who believe that men in white coats writing on prescription pads have some thing magical you can't get any other way."
Rosenfeld forecasts that when people find out about Sativex, they will start smuggling it and demanding to have it here. That market demand will eventually force the government's hand.
"I don't believe the government will allow [Sativex] in without more phase three studies to prove it's a legitimate medicine," he says. "But once that happens, they will be forced to deal with marijuana as a plant."
GW Pharmaceutical chairman Dr. Geoffrey Guy has admitted that his drugs could push U.S. agencies against the wall. In a rare interview in Cannabis Culture magazine, Dr. Guy said, "If our medicines are approved and being used across Europe, it is going to be hard for the U.S. to dismiss the process. They'd have to criticize U.K. doctors and institutions whose reputations are beyond question. They'd have to ignore the clear scientific evidence from a variety of clinical trials. They'd have to ignore the fact that our cannabis medicines are providing relief to patients that no other medicines can provide."
Indeed, in Nikkel's case, the prescription drugs she once took actually exacerbated her MS symptoms and reduced her quality of life. The testimonial page of GW's website features many patient statements along the order of "life was hell before I started using cannabis."
"When there are natural medications out there that can be used, I don't understand why people are having to suffer," says Nikkel. "With MS, there is no cure, so you want the best quality of life you can have. To me, that's the most important thing." - - ---