Phytocannabinoids and endocannabinoids: different in nature

Abstract

Cannabis is one of the earliest cultivated plants, of which Cannabis sativa and Cannabis indica are the most widespread and best characterized species. Their extracts contain (phyto)cannabinoids (pCBs) of therapeutic interest, such as Δ9-tetrahydrocannabinol and cannabidiol, along with many other compounds, so that there is no “one cannabis” but several mixtures even from the same plant. This complexity is mirrored, or even exceeded, by the complexity of the molecular targets that pCBs find in our body, most of which belong to the so-called “endocannabinoid (eCB) system”. Here, we describe the major pCBs and the main components of the eCB system to appreciate their differences and mutual interactions, as well as the potential of using pCB/eCB-based drugs as novel therapeutics to treat human diseases, both in the central nervous system and at the periphery. Moreover, we address the question of the evolution of pCBs and eCBs, showing that the latter compounds were the first to appear in nature, and that the former substances took a few million years to mimic the three-dimensional structures of the latter, and hence their biological activity in our body. Graphic abstract: [Figure not available: see fulltext.]