Photograph by Rory McNamara

Pain Pops: For now, Beckie Nikkel takes her medication in candy form–until the government sees fit to allow her legal methods.

How to Spell Relief: CANNABIS

Nature’s oldest drug is now the world’s newest pharmaceutical

By Mari Kane

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.”

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.”

For more information on GW Pharmaceuticals (London Stock Exchange: GWP), see www.gwpharm.com or Pharmos (Nasdaq: PARS), www.pharmoscorp.com.

From the October 9-15, 2003 issue of the North Bay Bohemian.

© Metro Publishing Inc.

The Sands of Time: Antenna’s ECOlogical calendar looks nothing like the old Gregorian stalwarts–and shows time in an entirely different light.

A Key to Slow Time

From the minds of Antenna Theater comes a whole new way of measuring our days in the universe

By Sara Bir

If the Eiffel Tower were now representing the world’s age, the skin of paint on the pinnacle-knob at its summit would represent man’s share of that age, and anybody would perceive that that skin was what the tower was built for. I reckon they would, I dunno.
–Mark Twain

About 13.7 billion years. According to NASA, that’s how long the universe has been around since the big bang banged. And before there were 12 months a year and seven days a week, the earth moved around the sun and the moon moved around the earth, and that’s what time was.

Enter the human. There was day and night and planting and harvest and winter, and that’s what time was.

From the time we are very young children, the months of the year are drilled into our consciousness. You know them by the date of your birthday and when school lets out for the summer and when holidays that mean presents come around. And then as an adult, calendars dictate our lives–rigid, faceless boxes and numbers stacked on top of each other.

Chris Hardman, artistic director of the groundbreaking Antenna Theater in Sausalito, decided it didn’t have to be like that.

For the past two years, Antenna has been working on a calendar that imagines the days of the year as threads that intertwine in a cosmic dance.

“It originally came out of a project called AllTime, which I started before the millennium,” says Hardman. “Being a theater company, would we do a big party and celebrate it as an important event in the history of mankind? The outcome was that the millennium was pretty meaningless–to be talking about 2,000 years is nothing in the real world of time. I started looking into the implications of having a calendar starting from the beginning of time.”

Antenna’s outcome was the ECOlogical calendar, which Hardman says will be the first calendar that will have the true age of the universe on it. They’ve been working on it for two years, and next year, Petaluma’s Pomegranate Communications, which specializes in calendars, posters, bookmarks, and cards, will put out a 2005 edition of the ECOlogical calendar.

To understand Hardman’s inspiration for creating a entirely new calendar, you need to understand where our present calendar came from. The Gregorian calendar was created in 1582 by Pope Gregory XIII and was largely based on the Julian calendar–which was largely based on the Egyptian calendar. “Julius Caesar just brought it back and said, ‘You, Romans, are now going to accept this calendar.’ He enforced it,” Hardman says. “The Julian calendar was so successful in terms of keeping in track with the solar year that it went on for 1,000-some years since its creation, all the way to Gregory.”

“The initial idea [for the ECOlogical calendar] was to pull the calendar back down to the earth experience itself,” Hardman says. “The only scientific and rational thing the Gregorian calendar has to offer us is it knows the actual time of the solar year. Other than that, it is essentially completely wrong about everything. It doesn’t start on a solstice or an equinox; it starts at a very arbitrary moment in time which has no natural connection to the earth and its orbit around the sun.”

The names of the months assigned to the Gregorian calendar have totally lost their meaning over time. Both July and August are named after dead Roman emperors, while the months September, October, November, and December have numerically derived names that don’t even apply anymore–i.e., December, the 12th month, is named for “deca,” or “10.”

Mary Russo McAfee, coordinator and manager of the AllTime project, did much of the research for the ECOlogical calendar. “We looked back at the way other cultures looked at the years. And then we started looking at the French Revolutionary calendar of 1793. Every single day had its own name. They had 12 months of 30 days, but that only added up to 360 days . . . so they tacked on five holidays. Every fifth day was an animal, and every 10th day was a farming implement. And everything else was an actual growing thing or something of the earth. We took a lot of inspiration from that.”

So for the ECOlogical calendar, they renamed the days and months, giving the passing of dates a poetic lilt instead of a dry, numerical feel. So instead of Jan. 9, 10, and 11, you have ClearNight, WindChill, and Rime.

“There’s no such thing called a week,” Hardman adds. “We’ve inherited a seven-day cycle, but that’s completely arbitrary and has no reflection to anything. Whereas the lunations of the moon actually do exist, and the seasons do exist. So we lay it down in a line so that you can experience all of these events as they are happening through time. You can also think of the ECOlogical calendar as a progression through space.”

That spatial relationship is reflected along the top of the calendar, where the sky’s position in relation to the Northern Hemisphere is illustrated, creating a map of the season’s sky. The phases of the moon, the tides, and the amount of sunlight in a day are also represented and accessible at a glance. It’s almost like an almanac in that way, only with a clear visual sense of continuity.

The ECOlogical calendar can be displayed a number of ways. It will have a threefold design, allowing it to be stood up on a mantel or desk, or the entire scroll can be posted on the wall for a more continuous reflection.

The ECOlogical calendar omits holidays but still lists the Gregorian dates and months. “This is the parallel universe we’re offering here,” says Hardman. “Whether people begin to adopt this calendar is something we can only offer. This is all essentially scientifically derived information that we can get from other sources. The only difference that we’re offering is that it’s experiential through the year. We try to give something that leaves you with a sense of where you are in that time.”

Antenna isn’t poised to push the ECOlogical calendar as the one new mode of keeping time. It’s more of a supplement, a key to unlock the cycles of nature that our modern lifestyles have pushed away. As everyone with a job knows, we can’t get by without knowing if it’s Monday the 22nd or Wednesday the 24th.

“People are going to continue to need that style of thing in their lives,” Hardman says of the Gregorian calendar. “What we’re saying is put our calendar above it and at least have a fighting chance to have a decent day and a good sense of the world that you’re in, ease that transition.”

“One of our main inspirations that we have,” Russo McAfee says, “is someone on the 40th floor in Manhattan can look at this and be somehow given that larger vision of what’s going on, and hopefully people will adjust their lives accordingly.”

If the ECOlogical calendar does find its audience, the spinoff possibilities include a journal/daybook with the information for each individual day listed on different pages, an interactive screen saver that changes daily, and Southern Hemisphere editions.

It used to be that our survival was dependent on identifying the cycles of nature so that we could anticipate them. “A hundred years ago, living on a farm, we’d know a lot of this stuff; you had to,” says Russo McAfee. “It was just passed on. The idea that nature isn’t something you go to a park for–nature is in you and around you–it’s really quite invigorating.”

“We were working off that sense of ‘Where am I in this picture?'” says Hardman. “‘How do I fit into this picture, and how can I relate to the larger picture?’ I’m always amazed that this hasn’t existed before. And I’m still trying to figure out why.”

For more information on the ECOlogical Calendar, go to www.ecologicalcalendar.info.

From the October 9-15, 2003 issue of the North Bay Bohemian.

© Metro Publishing Inc.