Snapshot of the cannabinoid receptor 1-arrestin complex unravels the biased signaling mechanism. (https://pubmed.ncbi.nlm.nih.gov/38101408/)

These scientists wanted to understand how a drug called cannabis works in our bodies. They focused on a specific part of our cells called the cannabinoid receptor 1 (CB1). When cannabis activates this receptor, it can help reduce pain and regulate our emotions. But it can also have some negative effects.

The scientists were particularly interested in a molecule called beta-arrestin-1 (betaarr1), which is involved in the way CB1 works. They wanted to study how betaarr1 interacts with CB1 and how it affects the way cannabis works.

To do this, the scientists used a special technique called cryo-electron microscopy. This technique allows them to take very detailed pictures of tiny molecules. They used this technique to take pictures of CB1 and betaarr1 together, while they were bound to a synthetic cannabinoid called MDMB-Fubinaca (FUB).

What they found was really interesting! The pictures showed that when betaarr1 is bound to CB1, it changes the shape of CB1 in a special pocket inside the cell. This causes a part of CB1 called TM6 to move outward and rearrange in a unique way. At the same time, FUB, the synthetic cannabinoid, also changes its position and goes deeper into CB1 compared to when CB1 is bound to another protein called G(i).

This discovery helps us understand how CB1 works differently when it interacts with betaarr1 and FUB. This knowledge can be useful for developing new drugs that target CB1 and have specific effects in our bodies.

Liao YY., Zhang H., Shen Q., Cai C., Ding Y., Shen DD., Guo J., Qin J., Dong Y., Zhang Y., Li XM. Snapshot of the cannabinoid receptor 1-arrestin complex unravels the biased signaling mechanism. Cell. 2023 Dec 21;186(26):5784-5797.e17. doi: 10.1016/j.cell.2023.11.017. Epub 2023 Dec 14.