Cell type specificity in CB1 antagonism
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Since the 1960s, much progress has been made in understanding Cannabis sativa’s mechanism of action. Focus on CB1, the G-protein coupled receptor held responsible for the psychoactive effects of marijuana and hashish, has led to multiple therapeutic applications. These include both appetite stimulation, by agonizing the receptor, and appetite reduction by antagonizing it. However, in the latter case, adverse have been noticed and the receptor seems to contain more complex properties than expected. These include constitute activity and possibly ligand specific activation of intracellular pathways. Utilizing these parameters in drug design might reduce adverse effects, while keeping the therapeutic force intact. Recently, astrocytes were shown to increase the release of neurotransmitters by endocannabinoids. This is in contrast with observations in neurons, where endocannabinoids show multiple forms of suppression of transmitter release. Activation of astrocytes by CB1 was shown to be mediated by other G-proteins than usual in neurons. Therefore, cell type specific inhibition of endocannabinoids’ effect is suggested to be possible. These results might be useful for further improving the balance between adverse and therapeutic effects of CB1 antagonists.