Chapter 1: Quest for Magic Bullets to Solve the Endocannabinoid Puzzle

Cannabis (Cannabis sativa and Cannabis indica) is one of the oldest cultivated plant. Its extracts contain >110 (phyto)cannabinoids (pCBs), some of which appear of clear therapeutic interest. Among them, ?9-tetrahydrocannabinol (THC) and cannabidiol (CBD) hold promise to treat several human diseases, both within the central nervous system and at the periphery. Yet, the complexity of cannabis makes it challenging to really exploit a specific active ingredient for a specific therapeutic purpose. This complexity of the plant extracts is mirrored, or even exceeded, by the complexity of the molecular targets that pCBs can find in our body, most of which belong to the so-called "endocannabinoid (eCB) system". Here, I describe the main components of this signalling system, in order to appreciate how challenging it is to develop drugs that can hit specifically each of them, with a benefit for human health.