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Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

Journal

PHARMACEUTICS
Volume 13, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics13111823

Keywords

phytocannabinoids; cannabigerol; cannabidiol; tetrahydrocannabinol; synthetic cannabinoids; cannabinoid receptors; endocannabinoid system; pharmacology

Funding

  1. Romanian Ministry of Education and Research, CNCS-UEFISCDI, within PNCDI III [PN-III-P4-ID-PCE-2020-1247]

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The discovery of the pharmacological effects of cannabis, traditionally used in Asia, has led to the development of new compounds for treating various diseases. Recent research suggests that these effects may not only involve cannabinoid receptors, but also other mechanisms yet to be fully understood.
The most important discoveries in pharmacology, such as certain classes of analgesics or chemotherapeutics, started from natural extracts which have been found to have effects in traditional medicine. Cannabis, traditionally used in Asia for the treatment of pain, nausea, spasms, sleep, depression, and low appetite, is still a good candidate for the development of new compounds. If initially all attention was directed to the endocannabinoid system, recent studies suggest that many of the clinically proven effects are based on an intrinsic chain of mechanisms that do not necessarily involve only cannabinoid receptors. Recent research has shown that major phytocannabinoids and their derivatives also interact with non-cannabinoid receptors such as vanilloid receptor 1, transient receptor ankyrin 1 potential, peroxisome proliferator-activated receptor-gamma or glitazone receptor, G55 protein-coupled receptor, and nuclear receptor, producing pharmacological effects in diseases such as Alzheimer's, epilepsy, depression, neuropathic pain, cancer, and diabetes. Nonetheless, further studies are needed to elucidate the precise mechanisms of these compounds. Structure modulation of phytocannabinoids, in order to improve pharmacological effects, should not be limited to the exploration of cannabinoid receptors, and it should target other courses of action discovered through recent research.

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