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Cannabis composition. The plant contains a large number of chemically active compounds, such as cannabinoids, terpenoids, flavonoids, and alkaloids. The most active components, which give its peculiar characteristics, are the ‘cannabinoids.’ Once considered the main active constituent in cannabis, ‘cannabinol,’ was isolated in the 1890s. Later, in the 1930s, ‘cannabidiol’ (CBD) was obtained. Then, in 1964, the primary psychoactive substance Δ-9-THC (l-delta-9-trans-tetrahydrocannabinol), was identified2424. Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc. 1964;86(8):1646-7. https://doi.org/10.1021/ja01062a046
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,2525. Mechoulam R. Plant cannabinoids: a neglected pharmacological treasure trove. Br J Pharmacol. 2005 Dec;146(7):913-5. https://doi.org/10.1038/sj.bjp.0706415
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. Subsequently, other cannabinoids were recognized, with some biological effects of their own or by modifying the results of Δ-9-THC. Currently, 538 natural compounds from Cannabis sativa are known, and more than 100 are identified as phytocannabinoids, which can be divided into ten subclasses, among which cannabigerol, cannabichromene, cannabidiol, tetrahydrocannabinol, Δ-9-tetrahydrocannabivarin, cannabicyclol, cannabinol, and other similar compounds. The proportion of these substances in the plant varies according to the species and to where it is grown. Thus, in temperate climates, the plant contains a small proportion of Δ-9-THC (with psychoactive properties) and a relatively high one of CBD (without psychoactive properties), while in hot climates (grown for its psychoactive effects), it contains a high proportion of delta-9-THC and relatively little CBD66. Brucki SMD, Frota NA, Schestatsky P, Souza AH, Carvalho NC, Manreza MLG, et al. Cannabinoids in Neurology - Brazilian Academy of Neurology. Arq Neuro-Psiquiatr. 2015 Apr;73(4):371-4. https://doi.org/10.1590/0004-282X20150041
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,77. Bonini SA, Premoli M, Tambaro S, Kumar A, Maccarinelli G, Memo M, Mastinu A. Cannabis sativa: a comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol. 2018 Dec;227:300-15. https://doi.org/10.1016/j.jep.2018.09.004
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,99. Pisanti S, Bifulco M. Medical Cannabis: a plurimillennial history of an evergreen. J Cell Physiol. 2019 Jun;234(6):8342-51. https://doi.org/10.1002/jcp.27725
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Endocannabinoid system. The site of action of the cannabinoids is the ‘endocannabinoid system,’ localized in the central and peripheral nervous systems, consisted of endogenous ligands, receptors, and synthesis and degradation enzymes, as proposed by Di Marzo et al. (1994)1515. Di Marzo V. A brief history of cannabinoidand endocannabinoid pharmacologyas inspired by the workof British scientists. Trends Pharmacol Sci. 2006 Mar;27(3):134-40. https://doi.org/10.1016/j.tips.2006.01.010
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. Its main receptors, comprising cannabinoid type-1 (CB1) and cannabinoid type-2 (CB2), were identified respectively in 1990 and 1993, and at the same period, the two endogenous CB receptor ligands were also discovered (AEA and 2-AG)77. Bonini SA, Premoli M, Tambaro S, Kumar A, Maccarinelli G, Memo M, Mastinu A. Cannabis sativa: a comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol. 2018 Dec;227:300-15. https://doi.org/10.1016/j.jep.2018.09.004
https://doi.org/https://doi.org/10.1016/...
,2525. Mechoulam R. Plant cannabinoids: a neglected pharmacological treasure trove. Br J Pharmacol. 2005 Dec;146(7):913-5. https://doi.org/10.1038/sj.bjp.0706415
https://doi.org/https://doi.org/10.1038/...
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