Cannabis can have a number of vastly different effects on human physiology, from stimulating hunger or laughter, to easing pain or causing paranoia. The reason for all these effects rests upon how the plant’s cannabinoids, or chemical compounds, interact with the body’s cannabinoid receptors throughout the endocannabinoid system.
For a while, scientists have believed that the CB1 receptors throughout the body worked only with THC, the main psychoactive compound in cannabis. Now they’ve discovered that CB1 receptors are more flexible than that — which means that scientists could eventually synthesize chemicals that fit the CB1 receptors like cannabis compounds do, but minus some of the undesirable effects that come with weed, like paranoia or federal prosecution.
There are already some synthetic cannabinoid medications on the market, such as Marinol or Nabilone, used to treat pain or nausea from chemotherapy. However, these medications do come with unwanted side effects.
As it turns out, THC and its synthetic copycats aren’t the only chemicals that can interact with the body’s CB1 receptors. Alexandros Makriyannis, co-author of the new research on CB1 receptors published in Nature, and director of Northeastern University’s Center for Drug Discovery, has already discovered dozens of other compounds that interact with CB1 receptors. He’s even discovered a compound that could turn the CB1 receptors off — and which has led him to his most recent discovery.
The molecules in THC and other cannabinoids that activate CB1 are about 100 times smaller than the receptor, itself. Makriyannis and his colleagues were able to visualize the CB1 receptor using X-ray crystallography, a technique that turns the molecule into a crystal, which allows X-rays to pass through to get an impression of it. With that impression, scientists can craft a visual representation of the molecule’s shape.
As it turns out, CB1 receptors are composed of a number of helices, smooth connected curves which surround the receptor’s binding site, and which makes it the receptor itself fairly malleable. The researchers found that in the presence of a THC-like molecule, the CB1 receptor was able to collapse around the molecule, meaning that it’s flexible enough to accommodate various different kinds of molecules.
According to Makriyannis, this is big news that will go nicely with future research as he discovers new cannabinoid molecules. “We want to make compounds that will modify the receptor differently, so we can make better drugs,” he says. He wants to synthesize molecules to fit and activate the CB1 receptor and ease nausea, without the side effects.
