Journal
BIOMOLECULES
Volume 12, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/biom12081084
Keywords
phytocannabinoids; minor cannabinoids; precannabinoids; decarboxylation; cannabinoid receptors; thermo-TRPs; PPAR gamma
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Funding
- MIUR Italy (PRIN2017) [2017WN73PL]
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Despite the focus on the major cannabinoids, research on the bioactivity of minor phytocannabinoids is limited but promising. This study categorizes the available bioactivity data into discovery, preclinical, and clinical stages and discusses strategies and challenges associated with the development of these minor phytocannabinoids as mainstream drugs.
Despite the very large number of phytocannabinoids isolated from Cannabis (Cannabis sativa L.), bioactivity studies have long remained focused on the so called Big Four [Delta(9)-THC (1), CBD (2), CBG (3) and CBC (4)] because of their earlier characterization and relatively easy availability via isolation and/or synthesis. Bioactivity information on the chemical space associated with the remaining part of the cannabinome, a set of ca 150 compounds traditionally referred to as minor phytocannabinoids, is scarce and patchy, yet promising in terms of pharmacological potential. According to their advancement stage, we sorted the bioactivity data available on these compounds, better referred to as the dark cannabinome, into categories: discovery (in vitro phenotypical and biochemical assays), preclinical (animal models), and clinical. Strategies to overcome the availability issues associated with minor phytocannabinoids are discussed, as well as the still unmet challenges facing their development as mainstream drugs.
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