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.

The Essential Medicinal Chemistry of Cannabidiol (CBD).

https://www.science.org/cms/asset/0743a932-dc07-4433-ae0e-cf615a182cc2/sciadv.abi6110.v1.pdf

Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses.

Boston and throughout the world. The course is designed for individuals who wish to gain basic and advanced training in clinical trials before moving into the field and for those who have experience in this area and aim to broaden their role in the design, management, analysis, and reporting of clinical trials. Participants can earn up to 72 (or 145.5 with all of the available optional workshops) AMA PRA Category 1 CreditsTM.

Principles And Practice Of Clinical Research

The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD induces interferon expression and up-regulates its antiviral signaling pathway. A cohort of human patients previously taking CBD had significantly lower SARS-CoV-2 infection incidence of up to an order of magnitude relative to matched pairs or the general population. This study highlights CBD, and its active metabolite, 7-OH-CBD, as potential preventative agents and therapeutic treatments for SARS-CoV-2 at early stages of infection.

/pdf/cannabidiol-inhibits-sars-cov-2-replication-and-promotes-the-19pu08d2m5.pdf

Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response

Background: Research on medicinal plants and extracts derived from them differs from studies performed with single compounds. Extracts obtained from plants, algae, fungi, lichens or animals pose some unique challenges: they are multicomponent mixtures of active, partially active and inactive substances, and the activity is often not exerted on a single target. Their composition varies depending on the method of preparation and the plant materials used. This complexity and variability impact the reproducibility and interpretation of pharmacological, toxicological and clinical research. Objectives: This project develops best practice guidelines to ensure reproducibility and accurate interpretations of studies using medicinal plant extracts. The focus is on herbal extracts used in pharmacological, toxicological, and clinical/intervention research. Specifically, the consensus-based statement focuses on defining requirements for: 1) Describing the plant material/herbal substances, herbal extracts and herbal medicinal products used in these studies, and 2) Conducting and reporting the phytochemical analysis of the plant extracts used in these studies in a reproducible and transparent way. The process and methods: We developed the guidelines through the following process: 1) The distinction between the three main types of extracts (extract types A, B, and C), initially conceptualised by the lead author (MH), led the development of the project as such; 2) A survey among researchers of medicinal plants to gather global perspectives, opportunities, and overarching challenges faced in characterising medicinal plant extracts under different laboratory infrastructures. The survey responses were central to developing the guidelines and were reviewed by the core group; 3) A core group of 9 experts met monthly to develop the guidelines through a Delphi process; and. 4) The final draft guidelines, endorsed by the core group, were also distributed for feedback and approval to an extended advisory group of 20 experts, including many journal editors. Outcome: The primary outcome is the “Consensus statement on the Phytochemical Characterisation of Medicinal Plant extracts“ (ConPhyMP) which defines the best practice for reporting the starting plant materials and the chemical methods recommended for defining the chemical compositions of the plant extracts used in such studies. The checklist is intended to be an orientation for authors in medicinal plant research as well as peer reviewers and editors assessing such research for publication.

/pdf/best-practice-in-the-chemical-characterisation-of-extracts-1les71og.pdf

Best Practice in the chemical characterisation of extracts used in pharmacological and toxicological research—The ConPhyMP—Guidelines

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.

https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fj.201902143R

Steven J. Casper

Papers

Improving Natural Product Research Translation: from Source to Clinical Trial