Phytocannabinoids and endocannabinoids: different in nature
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CANNABIS AND CANNABINOIDS
Phytocannabinoids and endocannabinoids: different in nature Mauro Maccarrone1,2 Received: 6 July 2020 / Accepted: 14 September 2020 / Published online: 15 October 2020 © The Author(s) 2020
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 Δ 9tetrahydrocannabinol 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 threedimensional structures of the latter, and hence their biological activity in our body. Graphic abstract
This article is a peer-reviewed paper originated from presentations at the Conference CANNABIS AND CANNABINOIDS— HISTORY, USES, AND SOCIO-ECONOMICAL IMPLICATIONS OF A CONTROVERSIAL PLANT held at Accademia Nazionale dei Lincei in Rome, 20 December 2019 organized by Vincenzo Di Marzo (Coordinator), Gennaro Marino, Jacopo Meldolesi, Daniela Parolaro. Extended author information available on the last page of the article
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Rendiconti Lincei. Scienze Fisiche e Naturali (2020) 31:931–938
Keywords Cannabinoid receptor · Bioactive lipid · Metabolic enzyme · Pharmacophore · Signal transduction · Vanilloid receptor
1 Introduction Cannabis is one of the earliest cultivated plants. When it is of industrial utility and culinary value, it is generally termed hemp; when it is bred for medical or recreational purposes, it is called marijuana. In both cases, the female plant produces a significant amount of bioactive and psychoactive compounds, but the existence of different species and cultivars of cannabis must be taken into account to evaluate their impact on health. Cannabis sativa and Cannabis indica are the most widespread and best characterized species of cannabis, and their extracts contain (phyto)cannabinoids (pCBs) of therapeutic interest, such as Δ9-tetrahydrocannabinol (Δ9THC) and cannabidiol (CBD), both shown in Table 1. Yet, the effect of cannabis extracts does not depend only on the amount of Δ9-THC and CBD, but also on the presence and concentration of > 110 additional pCBs, and > 440 nonphytocannabinoid compounds like terpenoids, flavonoids and sterols (Sohly et al. 2014; Solymosi and Köfalvi 2017). A
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