Beyond THC and CBD: Opportunities for Creating Pharmaceutical Targets: Page 2 of 2

December 18, 2019
Abstract / Synopsis: 

Taking a look back, we can see that the modern pharmaceutical industry evolved from more crude preparations and administration of natural product extracts. With consideration also given to what makes an effective therapeutic compound, it is interesting to think how the medicinal cannabis business will evolve through a similar lens.

Both Papaverine and Digitoxin illustrate the two ends of the spectrum of biopharmacologic efficacies using botanicals as medicine. One is too short, the other too long. To be a useful medication, a therapeutic agent should have a half-life in the body that allows for once or twice a day dosing, a therapeutic window that is wide, and minimal undesirable side effects relative to the primary action sought. However, knowing their structures and activities has led to a long-term and fruitful medicinal development of biologically inspired structures that improve human health.

Reviewing this history of bringing botanicals from anecdotal folk medicine through to science-based pharmaceuticals, we can expect the following as we take cannabis and hemp through the same journey. Initially, we should expect that any useful molecules may not be grown in sufficient quantities to fill the demand for an international market. Almost all of the molecules of interest that are present in cannabis and hemp (such as cannabinoids, terpenes, flavonoids), are expressed in exceedingly small quantities. Mendelian genetic manipulation is already being applied to amplify the concentrations of these constituents; however, laboratory genetic modification and chemical synthesis are also underway. The caveat with genetic modification is that this modality of increased production may also introduce or amplify compounds that interfere, inhibit, or produce side effects in a full-spectrum product, or they may delete compounds that are necessary for the full useful effect. Similarly, the production of individual cannabis and hemp-based compounds through chemical synthesis may produce products of limited therapeutic value.

This is in fact a major point of contention in the cannabis and hemp sectors. Anecdotal evidence already suggests that isolated use of either tetrahydrocannabinol (THC) or CBD does not match the beneficial effects of total extracts from cannabis and hemp. While the use of full-spectrum cannabis and hemp products is widely accepted, we can expect upon possible federal legalization that the pharmaceutical industry will apply regulatory and industry pressure to pursue only isolated molecules or their derivatives. In any eventuality, it is highly likely that newly isolated molecules will require chemical modification. The botanical molecule may have issues with biologic half life, target selectivity, or toxicity that limits or eliminates its use as a medication. Chemically modified analogues of cannabis derived molecules can produce a new species that overcomes these limitations. Regardless, investigation of purified molecules found naturally in cannabis and hemp are likely to indicate potential receptors that could be targeted through rational drug design, in which modifications to botanical progenitors lead to new avenues of clinical care.

The cannabis and hemp industries are in the midst of massive changes allowing for new frontiers in science to be more fully explored. Two things will limit the opportunity for medical advancement and discovery using cannabinoids, terpenes, and flavonoids: capitalization of that research and regulatory push back from U.S. federal authorities. As of this writing, the U.S. Food and Drug Administration (FDA) has issued three cease and desist letters for making false and unsubstantiated medical claims regarding the use of cannabinoids and it appears that there will be a fourth coming. Regulatory limits and possibly outright bans on the use of CBD as an additive and adulterant in multiple products are possible. Given the history of the FDA, we should expect that there will be an upcoming battle on the use of hemp and cannabis as nutraceuticals. The FDA may begin pushing for research into cannabis and hemp for use as ethical medications, while limiting or banning their use as nutraceuticals.  Only those who have started down the path of doing basic research into the safety and efficacy of cannabis and hemp, from the testing of isolated molecules and their modes of action through structured patient clinical trials, will survive.

About the Authors

Frank W. Foss Jr. and Kevin A. Schug are with the Department of Chemistry and Biochemistry at The University of Texas at Arlington, in Arlington, Texas. Direct correspondence to: [email protected] or [email protected]

How to Cite this Article

F.W. Foss Jr. and K.A. Schug, Cannabis Science and Technology 2(6), 62-64 (2019).