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Northeastern cannabinoids researcher developing drugs to fight pain and inflammation

Alexandros Makriyannis, director of the Center for Drug Discovery at Northeastern University, poses for a portrait holding up a flask of purple liquid.
Alexandros Makriyannis, director of the Center for Drug Discovery at Northeastern, has been awarded for his work developing cannabinoids. Photo by Alyssa Stone/Northeastern University

Associate cannabis with food and most people think of getting the munchies.

Alexandros Makriyannis, director of the Center for Drug Discovery at Northeastern University, however, is working on the opposite outcome. In the current project, the receptor is tweaked down.  He also produces compounds that tweak the receptor up.

“If you smoke cannabis you get hungry, you get fat,” says Makriyannis, Behrakis chair of pharmaceutical biotechnology and university distinguished professor at Northeastern. “So we do the opposite: We tweak the receptor down instead of tweaking it up, and these are molecules that could work for obesity and diabetes.”

Makriyannis founded the Center for Drug Discovery in 2003 and brought it with him when he came to Northeastern in 2005. The center conducts multidisciplinary research aimed at the discovery of new therapeutic medications. 

As director of the center, Makriyannis is at the forefront of developing new compounds that affect the endocannabinoid system — a vast network of chemical signals and cellular receptors throughout our brains and bodies that help regulate biological functions including eating, anxiety, sleep, pain control, inflammatory and immune responses and more.

The system reacts with cannabis and other compounds that can tweak the receptor up or down called cannabinoids.

“Cannabis has a lot of positive things, and there are a lot of people who believe in cannabis and believe that drugs can come out of it or cannabis itself can be useful for certain diseases,” Makriyannis says. 

But high amounts of increasingly potent cannabis can also be addictive, Makriyannis says. 

So, how do you harness the benefits of cannabis without triggering negative side effects?

“We study the constituents of cannabis and we also modify the molecules of cannabis, making them into new molecules and these new molecules have differential properties,” Makriyannis says. “We expect that sometime some of those would be developed into drugs.”

Makriyannis explains that the receptors don’t necessarily all react in the same way. They can be tweaked in either direction — amplifying some effects (for example, hunger) or decreasing other effects such as inflammation. 

So by manipulating cannabis molecules and creating new cannabinoids, the center is developing several different drugs that tweak the receptors to address pain, reduce inflammation, reduce hunger cravings and thus promote weight loss and treatments for diabetes and obesity, even reduce cravings for addictions.

The drugs are all in advanced preclinical stages.

The drugs, as well as the field of cannabinoid research and pharmaceutical development, show promise. 

“Next to morphine, cannabis is the next best way to reduce pain,” Makriyannis says. “And inflammation — also cannabis.”

In fact, his work in drug development as well as work identifying the function and structure of receptors and sensors in the endocannabinoid system — has earned Makriyannis the 2024 Center for Medicinal Cannabis Research Pioneer in Medicinal Cannabis Research Award. The CMCR award has only been given three other times in the organization’s 24-year history. 

“It’s a good honor,” Makriyannis says. 

He says, however, that the next few years are “critical” in advancing cannabinoids to market. 
“In the next five years there is a good opportunity, a good possibility, that they will start getting drugs in the market, and there should be at least three or four new drugs there,” Makriyannis says. “And we’re in the game.”