Flavonoids, Alkaloids, Terpenoids
Flavonoids, Alkaloids, Terpenoids: Non-Cannabinoid Natural Products of Cannabis
Author: Luke Khoury, Senior Scientist
Editor: Angelica Shubbie, Quality Systems Coordinator
Throughout the history of chemical sciences, natural product discoveries from various complex biochemical systems have caused paradigm shifts in medicine and engineering. By isolating, identifying, and differentiating natural products, researchers have developed a wide range of beneficial compounds utilized throughout the world. Aspirin (acetylsalicylic acid) was synthesized from the active ingredient in willow bark extract (salicin), likewise, natural products of Cannabis sativa L. appear to offer an array of beneficial applications. These range from novel therapeutic treatments to sustainable and renewable building materials (see hempcrete).1 Consequently, a mainstream dialogue regarding THC and CBD has entered a significant number of homes throughout the United States; seen with the growing acceptance of medical and recreational cannabis, is it possible a change in federal cannabis policy is gradually underway? One aspect is certain; the inevitable descheduling of cannabis under U.S. drug policy will allow fundamental research into the spectrum of cannabis-based natural products to flourish. Among these important naturally occurring compounds are flavonoids, alkaloids, and terpenoids which may influence future therapeutic methods.
These compounds belong to a class of biochemicals called secondary metabolites. Mostly occurring after the active growth phase, they are produced by routes other than normal biochemical pathways.2 Secondary metabolites may aid an organism in important functions such as protection, competition, and species interactions, but are not necessary for survival. In other words, plants such as cannabis will produce these phytochemicals if they are thriving or are physiologically stressed by their environment.
Flavonoids are a class of aromatic, polycyclic, oxygen-containing compounds, often with glycoside (sugar) linkages. Anthocyanins, natural pigment molecules, present a subtype of flavonoids which play a role in the phenotypic expression of purple and green hues signature of cannabis. Flavonoids are considered an essential component in a variety of nutraceutical, pharmaceutical, medicinal, and cosmetic applications, primarily due to their anti-oxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic properties in conjunction with their ability to modulate fundamental cellular enzyme functions.3 While cannabis contains approximately 23 flavonoid compounds, cannflavin A and B are two prenylated flavones unique to cannabis and have reported anti-oxidative properties.4,5
Fig. 1 Molecular structure of the flavone backbone (2-phenyl-1,4-benzopyrone).6
Similarly, researchers have found many beneficial applications for alkaloids, a diverse class of natural products containing one or more nitrogen atoms in a heterocyclic ring. Often considered to take part in an organism’s natural chemical defense, they have found application in human medicine as analgesics, anti-arrhythmics, anti-hypertensives, anti-protozoals, anti-tumors, stimulants, and vasodilators.7 One particular alkaloid, cannabisativine, has been found in the roots of cannabis.8 Moreover, researchers have sought therapeutic application of this naturally occurring alkaloid, as well as others found in whole root preparations, in potential treatment for inflammation and pain.9
Fig. 2 Molecular structure of cannabisativine, an alkaloid found in the roots of cannabis.10
While terpenoids are often a highly discussed component of cannabis’ chemical profile today, their diverse utility has long been explored. In a 1980 review, among 420 different constituents, researchers reported 58 monoterpenes and 38 sesquiterpenes from various cannabis preparations.11,12 Due to their diverse structural nature and biosynthesis in nearly all plants, research into therapeutic application of terpenes has been greatly supported. For example, researchers found anti-carcinogenic, anti-bacterial, anti-viral, anti-hyperglycemic, anti-inflammatory, anti-parasitic, anti-oxidant, and immunomodulatory activity in a wide range of terpenoid compounds.13,14 Certainly, these natural products play a role in the physiological response upon cannabis consumption; it is likely future studies will characterize these effects more precisely.
Fig. 3 Molecular structures of several terpenoid constituents common to cannabis, relative percent mass concentrations, boiling points, and reported potential therapeutic properties.15
Fig. 3 Continued
California’s modern legal cannabis market has stimulated the proliferation of a diverse array of products, many of which gained popularity initially as a consumer driven trend. Live-resin is a term colloquially used to describe a cannabis concentrate extracted from fresh biomass often harvested and immediately subjected to -40°C prior to processing. This material tends to be richer in cannabinoid acids, their neutral counterparts, terpenes, and potentially an abundance of other naturally occurring biomolecules. As the sophistication of cannabis extracts evolves in response to market trends, there is an expected increase in demand for the identification and quantification for non-cannabinoid constituents. Laboratories are equipped with the analytical techniques required; ranging from GCMS, LCMS, HPLC, and more. Ultimately, there are dozens of avenues available to explore this deeper chemistry. By partnering with labs of this caliber, cannabis operators and innovators may continue to push the boundaries of product development and continue to inspire researchers to study the spectrum of natural products found in cannabis.
- Bedlivá and N. Isaacs, “Hempcrete – An Environmentally Friendly Material?”, Advanced Materials Research, Vol. 1041, pp. 83-86, 2014. doi:10.4028/www.scientific.net/AMR.1041.83
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- Barrett, M. L., Scutt, A. M., & Evans, F. J. (1986). Cannflavin A and B, prenylated flavones from Cannabis sativa L. Experientia, 42(4), 452–453. doi:10.1007/bf02118655
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- Turner, C. E., Hsu, M. H., Knapp, J. E., Schiff, P. L., & Slatkin, D. J. (1976). Isolation of Cannabisativine, an Alkaloid, from Cannabis sativa L. Root. Journal of Pharmaceutical Sciences, 65(7), 1084–1085. doi:10.1002/jps.2600650736
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