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Monday, July 22, 2013

The science of medical marijuana is hard

David Brooks

From the scientific point of view, the idea of treating medical symptoms by smoking marijuana is, in a word, interesting.

That’s both good and bad. ...

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From the scientific point of view, the idea of treating medical symptoms by smoking marijuana is, in a word, interesting.

That’s both good and bad.

“Cannabis is just a very – a very interesting plant. It’s got all sort of compounds in it, and we frankly don’t know a lot about it,” said Dr. Alan Green, professor of pharmacology and toxicology, and chairman of the Department of Psychiatry at the Geisel School of Medicine at Dartmouth College.

Any effects of cannabis are the result of compounds called cannabinoids, of which the best-known is THC, the compound that correlates with getting high. These are taken up by two sets of molecular receptors – CB1, which is mostly in the brain, and CB2, which is mostly in other parts of the body – and alter the way the body handles electric and chemical signals that we feel as pain, nausea and other symptoms.

Synthetic versions of some cannabinoids have been created for decades: Wikipedia has a photograph of a “pre-1937” medicine labeled as fluid extract of cannabis indica, a species of marijuana, and these days a variety of cannabinoid medicines with names like Nabilone and Sativex exist as mouth sprays, pills or liquids, targeting pain, nausea (particularly from cancer chemotherapy), neurological disorders, appetite problems and other issues.

But their results are often limited with unpleasant side effects, which helps explain the push for medical use of smoked marijuana.

As Edgar Romero-Sandoval, a former Dartmouth medical researcher, put it in a 2012 presentation during a conference about medical marijuana: “Cannabis is claimed to produce a stronger analgesic effect than synthetic cannabinoids. This may be due to a complex combination of several components in the plant.”

“Complex” – that’s another word for interesting.

Green conducts research on the use of marijuana in people with severe psychiatric illnesses, trying to understand such things as why, for example, cannabis use appears to worsen schizophrenia. That makes him unusual: Not a lot of scientific study has been done on this subject.

“The research stands in a very preliminary place. There’s no medication on earth with this (low) level of research that would get by the (Food and Drug Administration),” said Dr. Alan Budney, a professor of psychiatry at the Geisel School and part of the Addiction Treatment and Research Program.

The lack is partly due of government constraints. Marijuana is classified as a Schedule I drug, meaning the federal government thinks it has “no medical value.” Just one location, at the University of Mississippi, grows marijuana legally for researchers, and its congressional mandate is to help understand the harmful effects of marijuana abuse, not possible helpful effects of controlled use.

The American Medical Association and the American College of Physicians have called for more research into therapeutic uses of marijuana, and for the U.S. government to reconsider its classification as a Schedule I substance, but nothing has changed at the federal level despite the push in states like New Hampshire to allow therapeutic marijuana.

Budney said the shortfall of good research also comes about because of the difficulty working with plants, which like all natural things can be variable in their content, then igniting them and inhaling not just the active ingredient but everything else.

“It’s really hard to do the research,” said Budney.

For example, he said, how can you develop a control when studying effects – a basic part of good scientific medical research. Do you create fake joints for people to smoke?

“It’s hard to give somebody smoked marijuana, and also have a placebo,” he said.

Smoking is bad for your lungs and marijuana can be addictive, so there’s a high risk/benefit ratio to consider when designing a study.

“Since it’s a drug that has abuse potential, you can’t just give it to anybody who walks in (and say), you haven’t smoked marijuana, let’s smoke marijuana,” he said. “If you’re doing a glaucoma study, you can’t just dose somebody for six weeks with significant amounts of marijuana to see what happens.”

Adding to the complication is that marijuana is an herb. The amount of cannabinoids can vary from plant to plant, just as flavor can varies from one tomato to another.

When you add in the differences between the way people smoke (cue the “don’t Bogart that joint” jokes), it’s difficult to administer a regular dose.

“Smoking a drug is not the ideal way to go about administering drugs,” said Budney.

Compared to ingestion, smoking has another effect, Green said: It acts much more quickly and often with more potency.

“Anything that’s smoked goes right into the lungs and from there into the heart and right to the brain, without even circulating,” said Green. “When you smoke cannabis – there is a very, very rapid increase in THC.”

By contrast, he said, taking a pill with THC means “it must be absorbed through the gut, then into the bloodstream. With oral THC, the blood level will never get as high.”

To sum up: marijuana is potentially useful but hard to understand as a medicine, hard to study scientifically, and smoking it makes everything even harder.


GraniteGeek appears Mondays in The Telegraph. David Brooks can be reached at 594-6531 or Follow Brooks on Twitter (@granitegeek).