We’ve known for a long time that marijuana, and its active compound, tetrahydrocannabinol (THC), can have a therapeutic effect. But while THC, and the associated cannabinoid molecule, can help in pain relief and muscle spasms, it can also have side effects ranging from anxiety to nausea.
However, if researchers can better understand how the molecule interacts with the receptor, it is possible they can develop a proxy that induces some of marijuana's beneficial effects while minimizing the negatives ones.
To explore this further, a new study published in the journal Nature used X-ray crystallography to in effect image the receptor as it bound to cannabinoid molecules. In doing so, the team found that our initial understanding of these cannabinoid receptors, known as CB1, was a bit off and that they are far more flexible and pliable than we previously thought.
It had long been thought that cannabinoid receptors and THC worked like a “lock and key” mechanism, in which the THC molecules are the key, fitting perfectly within the proteins on the surface of the cell that act like a lock. This latest study, however, has managed to decode CB1 in far more detail than ever before – and found that that's not exactly the case.
The team found that it was made up of seven sausage-like structures – themselves constructed of twists of amino acids – and that when the molecule landed on the binding site, the receptor physically changed shape to accommodate it. The ability of receptors to alter their structure is already well known, but this is the first time that it has been proven for those that adhere to THC and other related molecules.
It is thought that this great flexibility and malleability of the CB1 receptor could be exploited. If it can expand and twist to accommodate a wider range of molecules than previously thought, the researchers hope that they might be able to design new molecules that can replicate some of the effects created by THC, such as anti-nausea, but avoid others like anxiety and addiction.