Northeastern University researchers have made a breakthrough drug discovery, developing the first synthetic endogenous cannabinoid compound, with repercussions for new therapeutics from pain and inflammation to cancer.

Spyros P. Nikas, an associate research professor in Northeastern's Center for Drug Discovery, says that the discovery hinges on the distinction between two different kinds of cannabinoid chemicals, endogenous and exogenous. Exogenous cannabinoids are those produced outside the human body, like THC or CBD, both derived from the cannabis plant and present in marijuana.

Our own bodies, however, are also producing cannabinoids all the time. Called endogenous cannabinoids—or just "endocannabinoids"—these chemicals "modulate a wide range of physiological and pathophysiological responses," Nikas says, processes that include mood, inflammation and even neurodegenerative disorders like Alzheimer's and Parkinson's. The research is published in the Journal of Medicinal Chemistry.

Cannabinoids—not just cannabis
Endocannabinoids don't have the same structure as the plant-derived cannabinoids, "but they do exactly the same job," says Alexandros Makriyannis, the George D. Behrakis chair of the department of chemistry and chemical biology.

The cannabinoid system within the human body—"combining endocannabinoids, receptors and enzymes"—Nikas says, "exists everywhere with high abundance in the central nervous system."

Due to its prominence, Nikas calls it "a system that is responsible for the homeostasis of the human being."

The receptors that bind with cannabinoids, called CB1 and CB2, are also found throughout the body, but "they have different distribution in different tissues and organs," Nikas says.

Drugs that target the CB1 and CB2 receptors do exist already in medicine—for instance, to prevent vomiting in chemotherapy patients—but these are derived from the exogenous cannabinoids, and thus also exhibit the cannabis plant's side effects, from hallucinations to dependence, Nikas says.

Drugs derived from endocannabinoids "are not expected to have these side effects," Nikas says, as they are made inside our own, but the synthetic variety could still "have a wide range of therapeutic utility."

If researchers can produce synthetic endocannabinoids, they should come with all the medical benefits of our own naturally created endocannabinoids without the attendant side effects of exogenous cannabinoids. The problem is how unstable these synthetics usually are.