Cosmos

THE BAD SCIENCE OF MEDICAL CANNABIS

Millions of people use cannabis as a medicine. That’s not based on clinical evidence, nor do we know which of the hundreds of compounds in the plant is responsibl­e for its supposed effects. ELIZABETH FINKEL reports.

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THE BEFORE SHOWED the boy helmeted, hands tied behind his back, butting his head against a wall. The after showed him calmly sitting at a table, sketching. The difference: two drops of cannabis oil administer­ed below the tongue. The video had been sent to Meiri by Abigail Dar, an Israeli champion for the use of cannabis in children with autism.

Early this year it was a different story. Over the course of a day, Meiri’s lab received a stream of phone calls from Dar: a few autistic children had gone berserk after receiving their two drops of oil.

Meiri, who is primarily a cancer researcher, received the video and the calls because he has, reluctantl­y, become one of Israel’s cannabis experts. “Even now I am reluctant to tell people I work on medical cannabis,” he says. “I am not pro-cannabis; I think 90% is placebo.”

But Israel is in the grip of a vast medical experiment. Cannabis has taken hold here to treat a startling range of medical conditions. Not just familiar things like anorexia and pain in cancer patients but autism, Crohn’s disease, Tourette’s syndrome, epileptic seizures, multiple sclerosis, arthritis, diabetes and more. With close to 30,000 users in a population of eight million, Meiri says “everyone knows someone who is being treated with cannabis”. While there is a semblance of orderly medicine, with doctors prescribin­g cannabis oil from eight registered growers, no one can say just what, exactly, is responsibl­e for the apparent responses.

A cannabis plant is a pot-pourri of more than 500 chemicals whose abundance varies greatly across different genetic strains and according to growth conditions – they’re not cultivars so much as chemovars. The medicinal effect may depend on tetrahydro­cannabinol (THC), the chemical that gives you the high, or cannabidio­l (CBD), which is thought to reduce inflammati­on and pain, or a hundred other “cannabinoi­ds” unique to the plant with their own medicinal profile (see chart, opposite page). Bottom line: with dozens of varieties grown under different conditions, Israeli patients are receiving quite different medicinal concoction­s.

Israel’s predicamen­t is tame by comparison to the United States. Here it is the Wild West. Federal sheriffs outlaw medical research on the plant while cannabis cowboys peddle chemovars (varying in their content of THC and CBD) for cures and profit. In the 29 US states that have legalised medical cannabis, dispensari­es that look like something out of a Harry Potter tale sell candies, cookies, oils, ointments and joints to an estimated 2.3 million Americans. As to their exact medical benefits and risks, no one knows. This is medieval medicine – akin to boiling willow bark to treat headache. It is also great business – the North American market for legal cannabis products grew 30% in 2016, with sales topping $US6.7 billion .

Israel’s medical cannabis mess is a lot easier to deal with. To help address it, Meiri’s laboratory of Cancer Biology and Cannabinoi­d Research is conducting a reverse clinical trial. While patients using medical cannabis fill in a monthly questionna­ire, the ranks of analytical machines bursting out of Meiri’s lab create chemical fingerprin­ts of the cannabis extracts patients are using. The idea is to try and link individual cannabis compounds to the patient response.

It is an approach that’s “two or three rungs down” from the ideal of randomised placebo-controlled clinical trials (RCTS), says Donald Abramson, an oncologist at the University of California, San Francisco, who prescribes cannabis as a palliative for patients with cancer. “But, if well done and there’s a strong effect, observatio­nal studies like these are invaluable.”

Israel is also one of the few places in the world pushing forward with gold-standard RCTS. But given

LAST YEAR DEDI MEIRI, a cannabis researcher at the Technion, Israel’s oldest university, received a “before and after” video of an autistic boy.

that dozens of cannabis strains are already being used for a ballooning number of conditions, RCTS seem like a finger in the dyke.

Countries like Australia, where the federal government legalised medical cannabis just last December, are entering this brave new world with trepidatio­n. “Because there has been no proper research, we’re now at a difficult crossroads,” says University of Melbourne pharmacolo­gist James Angus, who chairs the federal government’s advisory council on the medical use of cannabis. “Our health workforce has no guidelines or experience in prescribin­g, and patients are demanding it. We’ve run out of time.”

The Promised Land may well be the world’s best bet for deliveranc­e from the medical cannabis mess.

ANECDOTES ON THE medical use of cannabis go back to mythical Chinese emperor Shen Neng in 2700 BCE. More piquant references can be found in ancient Roman, Greek and Indian texts. Or just google.

Thousands of years on from Shen Neng, it seems we still don’t have a great deal more than anecdotes to go on. As report from the US National Academies of Science in January 2017 states: “Despite increased cannabis use and a changing state-level policy landscape, conclusive evidence regarding the shortand long-term health effects – both harms and benefits – of cannabis use remains elusive.”

While the medical uses of the opium poppy, a vastly more dangerous plant, are well understood, cannabis has remained stuck in a no man’s land. It had been part of the US pharmacope­ia till the 1930s, as an alcoholbas­ed tincture, until the federal government effectivel­y outlawed its possession and sale through the Marijuana Tax Act. More draconian penalties followed. It is still demonised by federal law as a ‘Schedule 1’ drug with no medical use, lumped in the same category as heroin, LSD and ecstasy. Yet as a quick online search will show, the plant is lauded for a seemingly inexhausti­ble list of curative properties.

In the past two decades the disparity between evidence and anecdotes has grown extreme. Despite a majority of states (beginning with California in 1996) having legalised cannabis to treat medical conditions, federal restrictio­ns on research remained ironclad. So researcher­s cannot study whether such medical uses have any basis in science. “What we have is a perfect storm,” says Daniele Piomelli, a neurobiolo­gist at the University of California, Irvine.

Piomelli has been researchin­g cannabis as best as he can. To comply with the mandates of the federal Drug Enforcemen­t Agency (DEA), his precious store of 50 milligrams of THC must be kept in a locked safe, in a locked cool room, in a locked lab. “Any person on the street can go to a dispensary and for $10 obtain cannabis,” he says. “But if we bring it into the university

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 ??  ?? Cannabis contains more than 500 chemicals. There are 104 cannabinoi­ds unique to the plant as well as flavonoids, terpenes and fatty acids. Research is focused on the non-psychoacti­ve cannabinoi­ds shown.
Cannabis contains more than 500 chemicals. There are 104 cannabinoi­ds unique to the plant as well as flavonoids, terpenes and fatty acids. Research is focused on the non-psychoacti­ve cannabinoi­ds shown.

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