Towards systematically assessing bioactivity of natural compounds or bio-ligands: Cannabidiol as an example

Western medicine by law requires that drugs be synthetic compounds which are mass produced in heavily controlled manufacturing environments. In recent years there has been increasing interest in complementary and alternative medicine (CAM) for treating disease in the United States (e.g., White et al., 2017). Natural, non-vitamin, non-mineral dietary supplements account for a sizeable share of these approaches (17.7% in Clarke, Black, Stussman, Barnes, & Nahin, 2015). Despite their potential efficacy, a very small proportion of patients in the United States use CAM methods as complete replacements for standard pharmaceutical treatment (Nahin, Dahlhamer, & Stussman, 2010). Most CAM users reported taking natural dietary supplements for general wellness and preventative healthcare rather than specific outcomes (Marinac, Buchinger, Godfrey, Wooten, Sun, & Willsie, 2007). One reason is that identifying the dosages required for medicinal plant-derived compounds to treat specific diseases has proven difficult.

This was the case with cannabidiol (CBD). The CB2 receptor is a G-coupled protein receptor located predominantly in immune cells whose distribution and functions coincide closely with many observed immune effects of CBD (Ligresti, De Petrocellis, & Di Marzo, 2016). Despite hundreds of scientific articles written about CBD in recent times (Burstein, 2015; Zuardi, 2008), published displacement values (Ki) for the CBD/CB2 interaction continue to vary substantially. Inconsistent results such as these make dosage recommendations impossible (Thomas, 2017). To solve this problem, a novel approach was developed to predict CBD/CB2 binding affinity between samples (Cushing, Kristipati, Shastri, and Joseph, 2018). Plant source and processing factors were identified to alter CB2 receptor affinity of CBD.

It is estimated that 75-78% of all modern medicines are directly or indirectly derived from higher plants (Samuelsson, 2004). Less than 5% of all plant species have been explored for their medical potential (Chin, Balunas, Chai, & Kinghorn, 2006). Natural plant compounds rarely have side effects. This makes them a potent alternative to pharmaceutical drugs for chronic use.

All active ingredients from plants are biological molecules. They have a complex biochemical pathway to produce a somatic effect on the human body. In order for plant materials to rival pharmaceutical drugs, they have to undergo the same pharmaceutical factors – namely measurement of its bioactivity, knowledge of its pharmacokinetic and pharmacodynamic properties, and standardized quantities of active ingredient with the indential bioactive properties.

A three-step process for measuring bioactivity of all samples from natural plant-based sources will is outlined, using CBD as an example. This process is paramount for the application of natural plant-basedcompounds in western medicine.