On November 8, the voters in nine states will head to the polls to decide whether or not to legalize marijuana for recreational and/or medicinal use. Our country’s love affair with the herb isn’t difficult to understand—marijuana has been shown to have a number of potent medicinal qualities and is also a highly enjoyable way to pass an afternoon. In fact, the human body seems to be hardwired to use the stuff.
Humans, along with every other vertebrate possess a network of receptors in the brain specifically tailored to process a class of chemicals known as cannabinoids. This network is known collectively as the endocannabinoid system, and is largely comprised of two distinct set of receptors in the brain: CB1 and CB2. The former is present in large quantities in the brain and is responsible for the psychoactive effects of cannabinoids, and is the reason you feel stoned when you smoke weed. The latter is responsible for a much more restricted range of functions, particularly working with the body’s immune cells as an anti-inflammatory agent.
Although a wealth of research on the endocannabinoid system has been published over the years (some 20,000 research papers and counting), it was only last week that researchers have been able to create a 3D image of the CB1 receptor, which will provide insight into the way cannabis works in the brain as well as why some THC-related compounds produce harmful effects.
As detailed in Cell, in order to create a 3D image of the CB1 receptor the researchers had to produce a crystalized version of the cannabinoid receptor in order to get enough data about the receptor’s structure to produce a high-resolution 3D image. Once the team succeeded in crystalizing a CB1 receptor, they found that it had a complex “binding pocket network” which dictates how different compounds bind to the receptor and activate its effects.
In particular, the team was looking at AM6538, an chemical that binds particularly tightly to the CB1 receptor and is believed to be potentially useful for treating addiction.
A crystalized CB1 receptor with AM6538 antagonist. Imag: Liu, et al. / Cell
By having such a high resolution image of the CB1 receptor, the team is able to gain insight into how different agonists interact with the receptor and why compounds related to THC might have harmful effects, despite THC’s generally therapeutic properties.
As the team noted in their research paper, a number of CB1 agonists have been explored to treat things such as obesity-related metabolic disorders, mental illness and nicotine addiction. However the use of these agonists for medicinal purposes has been limited due to regulatory concern about serious side effects such as depression and anxiety.
By better understanding the way these agonists interact with CB1 receptors, the team hopes it will be possible to develop new treatments that address these issues without the unwanted side effects. It will also help facilitate marijuana’s acceptance as a medicine, allowing for more individually-tailored uses of America’s favorite flower.
In the words of Zhi-Jie Liu, the deputy director of the iHuman Institute of Shanghai Tech, “as marijuana continues to become more common in society, it is critical that we understand how it works in the human body.”