Researchers uncover structure of marijuana receptor that makes humans 'high'

Researchers have the clearest-ever picture of the receptor that gives humans the 'high' from marijuana, which could lead to a better understanding of how the drug affects humans.

Scientists have long known that molecules from THC, the psychoactive component of marijuana, bind to and activate the receptor known as CB1. But now they know that it has a three-dimensional crystal structure.

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The authors of the paper, which was published Thursday in the journalCell, say this information is crucial to improve our understanding of this receptor as marijuana use becomes widespread and, in many places, legalized.

Now that they know the shape of the receptor, they can get a better idea of how different molecules bind to it, which is what causes reactions in humans.

"What is important is to understand how different molecules bind to the receptor, how they control the receptor function, and how this can affect different people," said Raymond Stevens, co-author of the study.

Dr. Mark Ware, the executive director of the Canadian Consortium for the Investigation of Cannabinoids and the director of clinical research at the Alan Edwards pain management unit at the McGill University Health Centre, calledthe discovery a "breakthrough."

"Suddenly we've been given the design of the building," he explained. "We can work out ways to get in the building, we know where the windows and doors and stairs are, and we know kind of how the building is structured now."

They both said that knowing the receptor's design can lead to better drug design.

Synthetic 'Spice' and 'K2'

It's also a key step to understanding the differences between natural cannabinoids, found in the marijuana plant, and synthetic cannabinoids, made in labs.

Syntheticcannabinoidsare used in medicine, but some versions have surfaced as illegal drugs, known by names such as Spice and K2.

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"While overdose of THC/marijuana has not been documented, there have been cases of severe and even deadly responses to the ingestion of such synthetic mixtures resulting in federal restrictions by many countries, including the U.S.," the authors wrote in the study.

Synthetic THCcan 'prove toxic'

Stevens said the receptor behaves differently with synthetic compared to naturalcannabinoids, even though the synthetic ones are designed to mimic naturalcannabinoids.

"It remains unclear as to why THC can have such a high safety margin, while the synthetic cannabinoidconstituents can prove toxic with varyingseverityof serious side effects."

Synthetics used for some medical conditions

But many synthetic cannabinoids have been used to treat certain medical conditions safely for years.

These are very different from the syntheticcannabinoids"cooked up in basement labs," unregulated and sold on the street, said Ware.

"There are synthetic cannabinoids which are licensed as medicines in Canada now, which are reasonably safe as long as they're used under appropriate supervision," said Ware.

Synthetic cannabinoids are usedto treat nausea and vomiting in patients undergoing chemotherapy. It's also used to stimulate the appetite of patients with anorexia associated with HIV/AIDS. And others have been used to treat some symptoms suffered by patients with multiple sclerosis.

These have been used instead of natural cannabinoids because, until recently, Ware said it was very difficult to know what kind of a dose the patient would get from natural cannabinoids.

"If they were using an herbal cannabis product, they wouldn't know how much THC or any other compounds were in there, whereas with the synthetic pharmaceutical preparations it's a very defined dose," he said.

Synthetic cannabinoids also come with information about recommended dosages and possible side effects.

More research needed

As the use ofcannabinoidsas medical treatments becomemore and more common, there is a large gap in our understanding of how the drug natural or not actually works, said Ware.

Much of the information about the therapeutic benefits ofcannabinoidscomes from patients self-reporting, as opposed to from clinical trials.

"It's such a wide range of different conditionsthat it's not been possible to keep up on doing clinical studies on all the different conditions for which patients report cannabis being helpful," said Ware.

"That's not to say it doesn't necessarily work, but we don't have, and haven't had, the investment of time and money to do the studies required to get a better feel as to what's happening with those kinds of clinical experiences."

Ware said the discovery of what the receptor looks like greatly helps our understanding of how the drug works.

"But as a clinician and as somebody who sees patients asking about cannabis all the time, we need to be able to translate some of that basic scientific knowledge into clinical information which can be informative to patients," he said.

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