Researchers have pieced together the clearest picture to date of how THC binds to a specific cannabinoid receptor in the brain to produce the "high" associated with marijuana use.
                        
Medical marijuana

            

Marijuana is a flowering  plant the Cannabis  genus. Cannabis sativa and cannabisindica  are members of the nettle family that have grown wild throughout the world for centuries.


Medical cannabis or medical marijuana can refer to the use of cannabis and its cannabinoids to treat disease or improve symptoms; however, there is no single agreed upon definition. The use of cannabis as a medicine has not been rigorously scientifically tested, often due to production restrictions and other federal regulations. There is limited evidence suggesting cannabis can be used to reduce nausea and vomiting during chemotherapy, to improve appetite in people with HIV/AIDS,and to treat chronic pain and muscle spasms.


However,a new study was published in the journal ‘Cell’ about the 3D model of marijuana receptor in human brain. The scientist reveal how they have uncovered the structure of cannabinoid receptor 1 (CB1) - a receptor that is present on the surface of many nerve cells in the brain.


Using the information to create a 3-D model of the receptor, study co-author Raymond Stevens - a professor of Biological Science and Chemistry at the University of Southern California - and team have shed light on how THC and synthetically bind to the receptor.


Stevens and colleagues say their discovery could enhance the development of new marijuana-derived medications, as well as help to better understand the risks of marijuana use.


While marijuana remains the most commonly used illicit drug in the United States, its legalization for both medicinal and recreational purposes is widening.


With use of the drug projected to increase as a result, researchers believe it is more important than ever to fully understand how the active components of marijuana work in the body.

            

This image shows a drawing of the cannabinoid receptor, called CB1. The receptor is the yellow, ribbon-like structure, and it is shown bound to a stabilizing molecule called AM6538, which is represented by orange sticks. The active ingredient in marijuana, THC, is shown as yellow sticks. (The image of the receptor is superimposed over the shadow of a marijuana leaf and artistic smoke.)

            

How does the CB1 receptor works?

TheCB1 receptor is the main target of THC and synthetic cannabinoids - man-made substances that mimic the effects of THC - so the research team focused on finding out more about the structure of this receptor and how it works with specific molecules.


"[...]we need to understand how molecules like THC and the synthetic cannabinoids interact with the receptor, especially since we're starting to see people show up in emergency rooms when they use synthetic cannabinoids," notes Stevens.


The researchers synthesized AM6538 - a molecule known to tightly bind to and stabilize CB1 - and applied it to the CB1 receptor, which enabled them to determine the receptor's structure.


By creating a 3-D model of CB1, the team was able to get a more detailed understanding of how THC and synthetic cannabinoids work with the receptor to produce their mind-altering effects.


The researchers say their discovery could aid marijuana-derived drug development,and perhaps solve some of the problems that have already arisen with such medications.


For an example, the team points to a marijuana-based medication that was previously developed for the treatment of obesity; while it was effective against weight gain, the molecules in the drugs were found to trigger depression, anxiety, and suicidal thoughts.


"Researchers are fascinated by how you can make changes in THC or synthetic cannabinoids and have such different effects. Now that we finally have the structure of CB1, we can start to understand how these changes to the drug structure can affect the receptor,”says Raymond Stevens


Furthermore,the researchers say their model of CB1 could help researchers gain a better understanding of the side effects associated with synthetic cannabinoids, such as "spice" or "K2," which were responsible for almost 8,000calls to U.S. poison centers last year.


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, called the 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."

Stevens and Mark Ware both said that knowing the receptor's design can lead to better drug design.


"We need to understand how marijuana works in our bodies; it can have both therapeutic potential and recreational use, but cannabinoids can also be very dangerous," notes co-lead author Prof. Zhi-jie Liu, of the iHuman Institute at Shanghai Tech University in China.


"By doing both the basic science and understanding how this receptor works, we can then use it to help people in the future."

More study needed for understanding the receptor work

As the use of cannabinoids as medical treatments become more 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 of cannabinoids comes from patients self-reporting, as opposed to from clinical trials.


"It's such a wide range of different conditions that 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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