Updated: Jun 7
Welcome to Higher Learning LV's Study Summary series. This series reviews and summarizes peer-reviewed research studies and was developed specifically for cannabis industry professionals. These study summaries provide easily digested quick reads for a variety of important issues regarding the commerce and chemistry of legal cannabis.
A 2022 study entitled "The Phytochemical Diversity of Commercial Cannabis in the United States" that was published in the journal PLOS ONE investigated the chemical composition of tens of thousands of samples of loose-leaf cannabis flower in the largest study of its kind to date.
"Few studies have investigated the major and minor cannabinoids together with the terpenes and none have performed a thorough...analysis on a dataset with tens of thousands of samples across several regions of the United States," noted the study.
The study's authors proposed that an accurate mapping of "the chemical diversity of cannabis-derived products" that are consumed by tens of millions of Americans "has important implications for consumer health and safety." They noted that an identification of the "chemically distinct types of cannabis being consumed in legal markets" may be of value if these different types "are later determined to cause reliably different effects."
The researchers analyzed 89,923 different samples of loose-leaf cannabis from six certified testing laboratories in the U.S. states of Alaska (CannTest), California (SC Labs), Florida (Canna Labs), Michigan (PSI Labs), Oregon (ChemHistory), and Washington (Confidence Analytics).
The researchers analyzed 89,923 different samples of loose-leaf cannabis from six certified testing laboratories in the U.S. states.
The samples had been submitted by licensed growers and farmers to the certified labs as part of their compliance with their respective state laws (cannabis remains prohibited via Schedule I at the federal level). Each sample was tested for cannabinoid and terpene content, which was compared to "common industry labels and popularity metrics associated with them."
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The scientists defined "distinct chemotypes that reliably show up across U.S. states" and quantified how accurately the cannabis industry labels "indica," "sativa," and "hybrid" varieties. The study also examined the consistency of "strain" (cultivar) names across samples in terms of chemical composition.
The study observed that cannabis is a "flowering plant from the family Cannabacea" and that it is "one of the oldest domesticated plants," having been used by humans for more than 10,000 years. Cannabis has "spread throughout the globe such that distinct varieties or cultivars exist today, each having been cultivated to express certain phenotypes."
The study observed that cannabis is a "flowering plant from the family Cannabacea" and that it is "one of the oldest domesticated plants," having been used by humans "for more than 10,000 years."
"New laws leading to decriminalization and legalization have given rise to a global, multibillion dollar industry that is projected to continue to grow substantially," noted the study. It also reported that commercial cannabis is available to consumers in many forms other than flower, including "concentrated oils, beverages, topicals, suppositories, and other delivery mechanisms."
"Distinct chemovars, each with different ratios of cannabinoids and terpenes, are hypothesized to cause distinct effects for human consumers," wrote the study's authors.
The study explained two types of chemicals produced by cannabis, cannabinoids and terpenes. "Cannabinoids are a class of compounds that can interact with the endocannabinoid system and many have medicinal or psychoactive properties," it reported.
"Two of the most abundant cannabinoids are Δ-9-tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), which are converted to the neutral forms Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) once heated," noted the study. This process that converts non-psychoactive THCA into psychoactive THC and CBDA into CBD (both of which are non-psychoactive) is called decarboxylation.
The study's authors noted that commercial cannabis "usually falls within discrete groups based on THC:CBD ratio" and explained that three categories have emerged: 1) THC-dominant (low CBD levels), 2) CBD-dominant (low THC levels), and 3) Balanced THC/CBD (roughly equal levels of THC and CBD). The study added that the vast majority of commercial cannabis flower is THC-dominant.
Type I: THC-dominant cultivars
Type II: Balanced THC:CBD cultivars
Type III: CBD-dominant cultivars
"84.5 percent of CBD-dominant samples had total THC levels above 0.3 percent, the threshold used to legally define hemp in the U.S.," noted the researchers. "This indicates that a substantial fraction of CBD-dominant cannabis would not meet the legal definition of hemp in the U.S.," indicating a collision between the biochemical reality of this plant species and the regulatory framework wrapped around it in the United States.
The study also examined terpenes, "a diverse class of related compounds" that "play defensive roles for the plant" and are responsible for its odors and flavors. More important in terms of the scope of this particular study, the scientists also suggested that terpenes "may serve as reliable...markers for classifying cannabis beyond THC:CBD ratios," suggesting that terpene profile may be a reliable approach to improving upon the current industry standard labeling system of indica, sativa, and hybrid.
"The most common terpenes present in the flower samples were beta-caryophyllene (BCP), limonene, and myrcene."
The most common terpenes present in the flower samples were beta-caryophyllene (BCP), limonene, and myrcene (the most common terpene in cannabis, according to other studies). "In most cases, individual terpenes were rarely present at more than 0.5 percent weight," noted the research. Most terpenes were present "at low levels (< 0.2 percent) in a majority of samples," wrote the scientists.
Much speculation has been paid to the average weight by volume of terpenes in loose-leaf flower, with many industry professionals citing three to five percent levels. "Overall, total terpene content averaged two (2) percent by weight," reported the study. It also noted a "modest but robust positive correlation with total cannabinoid content" and suggested that "the production of one type of compound doesn't come at the expense of the other."
The study looked for correlations between certain terpene pairs that had been previously observed to display "robust" positive correlations. "Strong positive correlations were seen between alpha-pinene and beta-pinene, as well as beta-caryophyllene and humulene. These correlations were observed in both the overall dataset and also for each individual state."
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The research found that THC-dominant cannabis products (Type I) "displayed significantly higher levels of [terpene] diversity than both balanced THC:CBD [Type II] and CBD-dominant products [Type III]."
CBD-dominant and THC:CBD balanced products "displayed myrcene-dominant terpene profiles compared to THC-dominant samples."
To confirm its own findings, the study performed something called a bootstrapping simulation involving a random sampling of 245 products from each category and ensured equivalent sample sizes across different groups. It found that CBD-dominant and THC:CBD balanced products "displayed myrcene-dominant terpene profiles compared to THC-dominant samples."
The scientists observed many characteristics of the cannabinoid and terpene profiles of the thousands of cannabis flower samples, including some rules that seemed to apply to most or all samples. One of these commonalities was a dominance of the cannabinoid delta-9 THC.
"In all regions [of the United States], total THC levels were much higher compared to levels of all other cannabinoids," reported the study. "Total CBD and CBG were present at modest levels in some samples, while other minor cannabinoids were usually present at very low levels," it added.
"Historically, the major focus of both clandestine and legal cannabis breeding in the U.S. has been on THC-dominant (Type I) cultivars, which is why they predominate in the commercial marketplace," reported the researchers.
The "vast majority of variance in these cannabinoid profiles is explained by variation among the three most abundant cannabinoids (THC, CBD, CBG)."
The study noted that "3.9 percent and 23.1 percent of samples, respectively, had total CBD or total CBG of one (1) percent by weight or higher." It concluded that the "vast majority of variance in these cannabinoid profiles is explained by variation among the three most abundant cannabinoids (THC, CBD, CBG)" in the thousands of samples of commercial cannabis considered.
"Prevailing folk theories assert that 'indica' products provide sedating effects, 'sativa' energizing effects, and 'hybrids' intermediate effects," reported the study. "If this were true, we would expect to see a reliable difference between the chemical composition of samples attached to each [product] label."
The study found that the labels of indica, sativa, and hybrid did not correspond well to the terpene profiles of the samples. "It is likely that a sample with the label 'indica' will have an indistinguishable terpene composition as samples labelled 'sativa' or 'hybrid.'"
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The scientists determined that a simple product labeling system "in which THC-dominant samples are labelled by their dominant terpene" would better serve both the industry and consumers and be "better at discriminating samples than the industry-standard labelling system" of indica, sativa, and hybrid.
The study also found that cannabis flower samples of the same strain name, but from different cultivators or states, feature a wide range of chemical compositions (cannabinoid profiles and terpene profiles). This means that strain names may not serve as an accurate labeling system that allows patients, their wellness practitioners, and lifestyle consumers to reliably recommend or request products from commercial dispensaries when seeking particular outcomes.
The scientists determined that a simple product labeling system "in which THC-dominant samples are labelled by their dominant terpene" would better serve both the industry and consumers.
"Distinct 'strains' of THC-dominant cannabis are purported to offer distinct psychoactive effects, such as 'sleepy,' 'energizing,' or 'creative,'" reported the study. "While the commercial use of nomenclature is not accepted by the scientific community, it is conceivable that distinct chemovars of THC-dominant cannabis could cause different psychoactive effects."
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The study found "a large amount of variability in mean consistency scores across all 'strain names.'" Sometimes, the chemical makeup of a strain featured relatively strong consistency across the data set. For example, 96 percent of flower samples labeled to be the strain Purple Punch feature strong levels of beta-caryophyllene and limonene, while only 62.5 percent of products labeled Tangie fell into a single cluster.
"In all states, [cannabis flower] is comprised mostly of THC-dominant samples, each with a similar distribution of major terpenes and displaying the terpene-terpene correlations expected," summarized the study.
The study identified three cluster groups that each are dominated by a different terpene pair.
Cluster I: Relatively high levels of beta-caryophyllene and limonene
Cluster II: Relatively high levels of myrcene and pinene
Cluster III: Relatively high levels of myrcene and terpinolene
"Samples across these clusters display similar total THC distributions, while Cluster III is associated with modestly higher CBG levels," summarized the study's authors.
"The general approach we have used in this study can serve as a basic guide for cannabis product segmentation and classification rooted in product chemistry."
The scientists concluded that their study results "provide new possibilities for systematically categorizing commercial cannabis [products] based on chemistry, the design of preclinical and clinical research experiments, and the regulation of commercial cannabis marketing."
"The general approach we have used in this study can serve as a basic guide for cannabis product segmentation and classification rooted in product chemistry," they wrote. "Consumer-facing labelling systems should be grounded in such an approach so that consumers can be guided to products with reliably different sensory and psychoactive attributes."
View the original study.
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