Are There Limits to the Range of Possible Cannabinoid Ratios in Plants?: Page 2 of 6

March 12, 2020
Volume: 
3
Issue: 
2
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Figure 2 (click to enlarge)
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Abstract / Synopsis: 

Strikingly similar results have been reported from a wide range of studies on the ratio of tetrahydrocannabinol (THC) to cannabidiol (CBD) concentrations in strains of cannabis. Whether the source has been legalized markets in the west, medical markets in the U.S. and Canada, or collections from law enforcement and researchers, three easily distinguishable types of plant have consistently been found: THC-dominant strains (with less than 1% CBD); CBD-dominant strains (less than 1% THC); and balanced strains with comparable concentrations of both substances. Another consistent finding of these studies, carried out in a variety of laboratory settings, is a positive correlation between THC and CBD levels in those plants that can make substantial quantities (>1%) of each. The correlation between THC and CBD quantities in these varied populations suggests that there is a fundamental property of the plant that makes some combinations impossible, for instance, >15% THC and also >5% CBD. Such results have never shown up in published data sets of carefully, consistently tested samples, but those were all relatively small collections. A much larger data set has been released by the state of Washington (140,000 flower samples), and this has been scrutinized for evidence of consistently propagated strains with higher than a 2-to-1 ratio.

Molecular genetics techniques, not unlike those used to trace human ancestry, are now being used to investigate plants at the level of their DNA to determine how closely related they are. One study published this year in the Journal of Cannabis Research (1)  from the University of Northern Colorado examined the relatedness of 120 samples of cannabis from three legal Western markets, covering 30 named strains. Each strain studied was categorized according to its rating on the indica-sativa continuum as recorded by Leafly.com. Analysis of the strains’ genetic properties revealed poor alignment to the traditional labeling, leading the authors to conclude that “…there is no consistent genetic differentiation between the widely-held perceptions of Sativa and Indica Cannabis types” (1). Their conclusion corresponds with earlier work, notably a study from Sawler and colleagues (2), as well as another study from the University of British Colombia (3) and a study of the strains available in the Nevada medical market (4) that found much greater homogeneity in the genetic and cannabinoid profile than would be suggested by the profusion of strain names.

The accumulating evidence of the unreliability of the indica and sativa terminology has been a factor in the decision by Leafly to no longer categorize cannabis strains by those terms (5). Instead, that organization has recognized that the cannabinoid profile of cannabis plants is better described by one of three terms: tetrahydrocannabinol (THC)-dominant, cannabidiol (CBD)-dominant, or balanced. The evidence that supports this fundamental distinction among all cannabis plants is detailed in the next section.

Converging Evidence for Three Categories of Cannabis

A range of studies during the past 15 years have established that the relative quantities of THC and CBD in cannabis plants occurs in only one of three patterns. An assortment of investigations has produced this insight: studies of genetic crosses; studies of the DNA sequences of cannabinoid synthesizing enzymes; and numerous studies of the cannabinoid profile of strain collections from medical and recreational markets. A wide range of such potency studies, using very different collections of strains, has produced strikingly similar results.

The great similarity in the results of studies of cannabinoid ratios in collections of strains from a wide range of sources points to a fundamental property of cannabis plants that is found no matter where they are cultivated. Across these many strain sources and testing laboratories, the consistent finding is that the relative quantities of THC and CBD can only be in one of three patterns: either there are equivalent concentrations of both substances; or one compound is dominant, with only trace levels of the other. Evidence supporting this three-part classification is presented here from five studies. Each of these studies used a scatter plot to display the relative amounts of THC and CBD in individual strains, and in each of these charts the data points separate neatly into three clusters.

The earliest study in this group was a 2003 cross-breeding experiment by de Meijer and colleagues that examined the offspring of high THC plants crossed with high CBD plants, and their progeny (6). The scatter plots (Figure 1) of the THC (y-axis) and CBD content (x-axis) show three distinct clusters. High THC plants (with little CBD) are clustered on the y-axis, the high CBD (and low THC) plants are clustered on the x-axis, and the cluster that sloped up the middle of the chart had comparable quantities of each. The 1:2:1 ratio of the three types in the progeny of the crosses was interpreted by the authors as evidence for one genetic locus, with two codominant alleles, that control the relative quantities of THC and CBD.

A study from the University of Indiana (7) examined 157 strains of cannabis that were collected from breeders, researchers, gene banks, and law enforcement. The cannabinoid profile in that disparate collection of strains conforms very closely to the three cluster result of the cross-breeding study (Figure 2). Similarly, a 2015 study of 210 strains from the Canadian medical program’s License Providers demonstrated the same clustering of three types in scatter plots (Figure 3) of THC and CBD concentrations (with the x- and y-axes reversed from the earlier figures). A comparable study of 245 strains tested in New Jersey’s medical marijuana program (8) revealed the same pattern of three clusters: THC-dominant, balanced, and CBD-dominant strains, though the vast majority of the strains tested in the New Jersey medical program were the THC-dominant type (Figure 4). (See upper right for Figures 1-4, click to enlarge.)

References: 
  1. A. Schwabe and M. McGlaughlin, J. Cannabis Res. 1, 3 https://doi.org/10.1186/s42238-019-0001-1 (2019).
  2. J. Sawler, J. Stout, K. Gardner, D. Hudson, J. Vidmar, L. Butler, J. Page, and S. Myles, PLoS One 10(8), https://doi.org/10.1371/journal.pone.0133292 (2015).
  3. E.M. Mudge, S.J. Murch, and P.N. Brown, Scientific Reports 8, 13090 https://doi.org/10.1038/s41598-018-31120-2 (2018).
  4. U. Reimann-Philipp, M. Speck, C. Orser, S. Johnson, A. Hilyard, H. Turner, A. Stokes, and A. Small-Howard, Cannabis and Cannabinoid Research https://doi.org/10.1089/can.2018.0063 (2019).
  5. https://www.leafly.com/info/cannabis-guide.
  6. E. de Meijer, M. Bagatta, A. Carboni,  P. Crucitti, V. Moliterni, P. Ranalli, and G. Mandolin, Genetics 163, 335–346 (2003).
  7. K. Hillig and P. Mahlberg, Amer. J. Bot. 91, 966–75 (2004).
  8. T. Coogan, J. Cannabis Res. 1, 11 https://doi.org/10.1186/s42238-019-0011-z (2019).
  9. N. Jikomes and M. Zoorob, Sci. Rep. 8, 4519 https://doi.org/10.1038/s41598-018-22755-2 (2018).
  10. https://doi.org/10.7910/DVN/E8TQSD.

 

About the Author

Thomas A. Coogan, PhD, is an Academic and Research Liaison with the New Jersey Cannabis Industry Association. Direct correspondence to: [email protected]

 

How to Cite this Article

T.A. Coogan, Cannabis Science and Technology 3(2), 32–39 (2020).