Professor Alexandros Makriyannis’ Groundbreaking Research on Cannabis

February 23, 2020

BOSTON – Professor Alexandros Makriyannis, the George D. Behrakis Endowed Chair of Pharmaceutical Biotechnology and Director of the Center for Drug Discovery at Northeastern University in Boston, recently completed the full characterization of the two cannabinoid receptors, News @ Northeastern reported.

Smoking marijuana can produce such effects as feeling excited, giddy, relaxed, hungry, sleepy, and even paranoid, as tetrahydrocannabinol, the main psychoactive compound in marijuana, affects sensations for people who may use it to cope with a variety of health problems. The molecules known as cannabinoids also occur naturally in the body in the endocannabinoid system which regulates mood, appetite, and other sensations.

Prof. Makriyannis told the News @ Northeastern that “there are many ways to design new molecules in the lab to tweak that endocannabinoid system and control several of the biochemical reactions that lead to anxiety, chronic pain, and other physiological processes.”

Makriyannis is researching ways to synthesize the cannabinoid molecules so people can experience the benefits without the negative effects. “We can produce medications for pain, medications that deal with liver diseases, with sleep—a wide variety of these by making molecules that can turn these switches on or off more precisely,” Makriyannis told the News @ Northeastern.

Makriyannis was part of a team of scientists whose findings were published in Cell magazine and which “revealed for the first time the complete, three-dimensional structure of the body’s endocannabinoid receptors, the proteins in our cells responsible for the effects of cannabinoids,” the News @ Northeastern reported, adding that the “findings present a snapshot that provides a full view of the structure of cannabinoid receptor type two, or CB2, one of the two types of cannabinoid receptors in our cells.”

“The newly unveiled structures are enabling scientists to account for the effect of cannabinoid molecules such as tetrahydrocannabinol on the body, and will also be used to develop novel therapeutic medications,” Makriyannis told the News @ Northeastern.

“You could use this as a basis to develop new molecules, new keys that could modulate the function of this protein. We can make them in different flavors, for different conditions,” he said, the News @ Northeastern reported.

All cells “are coated with two types of proteins that are exclusively receptive to cannabinoid compounds” the News @ Northeastern reported, adding that “Makriyannis thinks of these receptor proteins as switches” and he says that “cannabinoids act as special keys that turn those switches on and off in different ways.”

“Once you know the structure of this receptor, you can get the mechanism of how it produces different effects when modulated. If you change that key, you might get a different type of an effect,” Makriyannis told the News @ Northeastern.

Makriyannis “focuses on mapping the exact structure of cannabinoid receptors to make new molecules that would fit neatly with their shape to control different functions within the endocannabinoid system,” the News @ Northeastern reported.

Though very similar, “cannabinoid receptor type one, or CB1, plays a key role in controlling appetite and mood disorders,” and “CB2 is involved in the immune system, in diseases such as cancer and fibrosis in the liver and kidney,” the News @ Northeastern reported.

“With the right molecule, these receptors could be switched on and off at will for targeted therapeutic medications,” Makriyannis told the News @ Northeastern, adding that “you can make them turn off completely, or partly turn them on—or super turn them on, or you can turn them on in the brain, or turn them on in the liver but not in the brain—you can play a lot, and that’s what we’ve been doing.”

Having previously mapped the structure of CB1 in 2016, CB2 in the off configuration in 2019, and now completed the mapping for CB2, Makriyannis’ team “has now completed a roadmap that reveals the different mechanisms in which both types of receptors are activated or deactivated,” the News @ Northeastern reported.

Makriyannis and other scientists can now work on improving new molecules “that will lead to improvements in various therapeutic treatments,” he told the News @ Northeastern.

“One of our more advanced compounds is what one might call a neutral cannabinoid 1 antagonist. We are trying to develop it in humans to deal with diseases of the liver, especially liver cirrhosis and liver fibrosis,” Makriyannis said, the News @ Northeastern reported, adding that “another compound that is a CB2 agonist, which turns the CB2 receptor on, can protect people from neuropathic pain.”

“We’re also developing a pill to be taken before going to sleep, which is one of the most difficult parts of PTSD,” Makriyannis told the News @ Northeastern.



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