This Perspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labeled health products and CBD-associated health claims lacks a rigorous scientific foundation. CBD's reputation as a cure-all puts it in the same class as other "natural" panaceas, where valid ethnobotanicals are reduced to single, purportedly active ingredients. Such reductionist approaches oversimplify useful, chemically complex mixtures in an attempt to rationalize the commercial utility of natural compounds and exploit the "natural" label. Literature evidence associates CBD with certain semiubiquitous, broadly screened, primarily plant-based substances of undocumented purity that interfere with bioassays and have a low likelihood of becoming therapeutic agents. Widespread health challenges and pandemic crises such as SARS-CoV-2 create circumstances under which scientists must be particularly vigilant about healing claims that lack solid foundational data. Herein, we offer a critical review of the published medicinal chemistry properties of CBD, as well as precise definitions of CBD-containing substances and products, distilled to reveal the essential factors that impact its development as a therapeutic agent.
Bibliographical noteFunding Information:
The K determinations, receptor binding profiles, agonist and/or antagonist functional data, HERG data, MDR1 data, etc. as appropriate were generously provided by the National Institute of Mental Health’s Psychoactive Drug Screening Program, Contract HHSN-271-2018-00023-C (NIMH PDSP), directed by Dr. Bryan L. Roth at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda, MD, U.S. The authors acknowledge the following financial support: J.L.D. through Grant T32 HL007627 from NHLBI/NIH; J.B., J.G.G., S.-N.C., and G.F.P. through Grants U41 AT008706 and P50 AT000155 jointly from ODS/NIH and NCCIH/NIH. Furthermore, the authors acknowledge the collegial spirit of Drs. Young-Hae Choi and Rob Verpoorte, University of Leiden, for kindly sharing their historic raw NMR data. J.L.D. gratefully acknowledges Drs. Parnian Lak and Brian Shoichet for performing DLS experiments. We kindly acknowledge the Research Open Access Publishing (ROAAP) Fund of the University of Illinois at Chicago for financial support towards the open access publishing fee for this article. Finally, the authors thank M. Backmann for help in creating the figure for the graphical abstract. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The opinions or assertions contained herein belong to the authors and are not necessarily the official views of the funders. i
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