Structural basis of selective cannabinoid CB receptor activation

Selectively easing pain and inflammation

31 July 2023

An experimental drug that selectively targets a cannabinoid receptor but not a closely related one, could alleviate pain and inflammation while sidestepping the psychotropic and other side effects of other cannabis-based compounds.

The use of compounds isolated from cannabis for treating various diseases, including cancer and neuropathic pain, stretches back centuries.

Activation of the cannabinoid CB₂ receptor (CB₂R), which is mostly found in immune cells, can alleviate inflammation associated with tissue injury. Several CB₂R-selective compounds are known, but the basis of their selectivity is unclear.

Now, a team co-led by researchers from ShanghaiTech University in China has developed a new selective CB₂R agonist, and investigated how such compounds interact with the receptor.

The team showed that, compared to CB₁ receptor (CB₁R), CB₂R had a distinct activation mechanism and a binding pocket accessible by different routes depending on agonist polarity. The insights could guide future drug design.

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References

1. Nature Communications 14, 1447 (2023). doi: 10.1038/s41467-023-37112-9