Why does cannabis get you high? What is it about the psychoactive component in marijuana, THC, or tetrahydrocannabinol, that exerts its special effects? Researchers hoping to use THC as a therapeutic agent in medicine, for treating symptoms of multiple sclerosis and other painful disorders, for instance, and others seeking to understand drug addiction would certainly like to know.
New clues about the cannabinoid receptor type 1 (CB1), which is hit by THC and is present throughout the central nervous system have now emerged thanks to Krisztina Monory and her colleagues at the Johannes Gutenberg University Mainz, Germany. Monory and her colleagues have used an advanced genetic approach to obtain the precise anatomical and neuronal substrates of each of THC’s actions.
In their study, the researchers studied mice that lack the gene for the CB1 receptor in specific areas of their central nervous system. Whether or not the mice would get “high” was not known in advance. Indeed, it was the specific genetic knockout and the way the mice behaved after exposure to THC that would reveal particular details of which parts of the nervous system are affected and how.
So, the mice were treated with THC, and typical effects of the drug on movements, pain threshold, and heat tolerance were scored. The results show that several important pharmacological actions of THC do not actually depend on the functional expression of CB1 on a specific kind of nerve cell known as a GABAergic interneuron, but do require the receptor to be expressed on other types of nerve cells. The researchers say that this discovery could pave the way to a refined interpretation of the pharmacological effects of cannabinoids on the nervous system, which could improve the development of analog compounds that have medicinal benefits without the “high”.
PLoS Biol, 2007, 5, e269