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. 2020 Dec 12;16(7):1433–1435. doi: 10.4103/1673-5374.301011

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Copyright: © 2021 Neural Regeneration Research

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Schematic representing terpenes, polyphenols, and flavonoids—phytocannabinoid ligands beyond the Cannabis plant—(just) the tip of the iceberg!

Currently, different phytocannabinoids have been isolated from the Cannabis sativa plant, such as Δ9- tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), cannabinodiol (CBND), flavonoids, essential oils and others, referred to as the “full cannabinoid spectrum”. Terpenes, polyphenols, and flavonoids are a widespread group of secondary metabolites found in several plant families, including Cannabaceae and others. Altogether, cannabinoids, polyphenols, flavonoids, terpenoids, and essential oils extend the therapeutic benefits of each compound, known as the entourage effect. Thus, cannabinoid-like molecules, for instance, terpenes, polyphenols, and flavonoids beyond the Cannabis plant, can act as cannabinoid receptor agonists or antagonists, or endocannabinoid system enzyme inhibitors, and are able to play a role in different pathological conditions, including neurodegenerative and neuropsychiatric-related disorders. These compounds normally occur in numerous plant species, such as terpineol (Punica granatum L.), citral (Cymbopogon citratus), β-caryophyllene (Pterodon emarginatus, Cordia verbenacea and Copaifera reticulate), terpinene (Eucalyptus genus), limonene (Citrus limonum and Citrus sinensis L.), pinene (Lavandula angustifolia), elemene (Curcuma rhizome), falcarinol (Panax ginseng), celastrol (Tripterygium wilfordii), euphol (Euphorbia tirucalli), nerolidol (Baccharis dracunculifolia), salvinorin A (Salvia divinorum), amorfrutins (Helichrysum umbraculigerum), perrottetinene (Radula perrottetii and Radula marginata), machaeridiol (Machaerium multiflorum), ferruginene (Rhododendron ferrugineum), amyrin (Bursera and Protium species), pristimerin (Celastraceae family), betulinic acid (Betula platyphylla), magnolol (Magnolia officinalis), kaempferol (Aloe vera) and quercetin (Calendula officinalis, Crataegus monogyna, Matricaria chamomilla, Hypericum perforatum, and Ginkgo biloba).