Study Summary: Terpenes—From Plant to Humans

A 2019 study entitled "Terpenes in Cannabis Sativa—From Plant Genome to Humans" that was published in the journal Plant Science explored the "hundreds of different terpene and cannabinoid metabolites" produced by cannabis. The peer-reviewed study noted that research about cannabis "is lagging...compared to other high-value crops."

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"Our understanding of the genomic and biosynthetic systems of these metabolites in cannabis, and the factors that affect their variability, is rudimentary," reported the study's authors. They noted an industry-wide concern about a "lack of consistency with regard to the terpene and cannabinoid composition of different cannabis 'strains.'"


The study noted that humans have been domesticating cannabis for more than 5,000 years. "The most valuable cannabis product today is the terpene- and cannabinoid-rich resin with its various psychoactive and medicinal properties," noted the researchers.


Understanding Terpenes

The study reported that more than 150 terpenes and "approximately 100 different cannabinoids" have been discovered in "different cannabis types." "While cannabinoids are the primary psychoactive and medicinal components of cannabis resin, volatile terpenes (monoterpenes and sesquiterpenes) contribute many of the different fragrance attributes that influence consumer preferences," noted the study.


"Volatile terpenes (monoterpenes and sesquiterpenes) contribute many of the different fragrance attributes that influence consumer preferences," noted the study.

"Different cannabis types and their derived consumer products are commonly referred to with 'strain' names," wrote the scientists. "These names often relate to fragrance attributes conferred, at least in part, by terpenes."


The research stated that "a history of largely illicit cannabis production" means that cannabis cultivars ("strains") "are often poorly defined genetically. [Cultivars] may lack reproducibility with regard to profiles of terpenes and cannabinoids."


It reported that the cannabis species involves significant genetic diversity. "As a result, many cannabis [cultivars] lack the level of standardization that producers and consumers are accustomed to with other crop plants, such as genetically and phenotypically well-defined grapevine varieties," wrote the scientists.


Terpene Research Needed

The researchers noted that, while some is known about the effects of popular cannabinoids such as CBD and THC in humans, little is known about the efficacy of terpenes when consumed in the average volumes in which they are found in modern cannabis loose-leaf flower cultivars and other products (such as extracted concentrates).

"While some of the effects of the cannabinoids have been scientifically explained, there is a great deal of uncertainty about the effects of cannabis terpenes in humans beyond fragrance perception," noted the scientists.


"The proposed synergistic effects of terpenes [from] cannabis in humans is an area that will require careful research, which will now be possible in those jurisdictions in which some of the legal restrictions have been lifted," observed the study.


Terpene Composition

"Terpene composition is a phenotypic trait that shows much variation across different cannabis [cultivars]" noted the study's authors. Despite this variability, the study reported that three terpenes "appear to be present in most cannabis [cultivars]: Monoterpene Myrcene [the most common terpene in cannabis] and sesquiterpenes β-caryophyllene and α-humulene."


The study noted that other common terpenes include monoterpenes alpha-pinene (the most common terpene in the world), limonene (the second most common terpene in the world), and linalool. In addition, "the sesquiterpenes bisabolol and β-farnesene" are also common.

The study noted that other common terpenes include monoterpenes alpha-pinene (the most common terpene in the world), limonene (the second most common terpene in the world), and linalool. In addition, "the sesquiterpenes bisabolol and β-farnesene" are also common.


Difficult to Identify

"It is important to note that some terpenes, in particular sesquiterpenes, remain difficult to identify due to the lack of authentic standards for many of these compounds," reported the study. As a result, reports of terpene profiles (certificate of analyses, or CoAs) "may include unknown compounds, rely on tentative identification, or present incomplete profiles...."


The study explained how monoterpenes (the most simple class of terpene) and cannabinoids have a common chemical component, a "ten-carbon isoprenoid precursor," but that the more complex sesquiterpenes are produced from a fifteen-carbon isoprenoid.

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The study noted that the unique terpene profiles of individual cultivars "may also substantially change as a result of differential...gene expression over the course of plant development or in response to environmental factors." The study lamented that none of these issues regarding terpene variation "which may contribute to poor reproducibility of terpene composition" have been systematically studied.


The study noted that various environmental aspects of plant cultivation, including "light, irrigation, and nutrients" can dramatically affect terpene expression and profile at time of harvest.

The scientists described how the ability to reliably reproduce particular terpene profiles in commercial cannabis cultivars requires "rigorous studies with a diversity of cannabis genotypes grown under controlled environmental conditions" and that such research must include "organ-, tissue- and cell-type specific terpene analysis."


The study noted that various environmental aspects of plant cultivation, including "light, irrigation, and nutrients" can dramatically affect terpene expression and profile at time of harvest.


Terpenes & Entourage Effect Theory

The scientists explained how the entourage effect theory is a "popular idea" that proposes that there is a "pharmacological synergy" between cannabinoids and terpenes (and perhaps other chemical components of cannabis resin, including esters, acetates, and flavonoids, among many others).

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Proponents of the entourage effect theory point to the common terpene β-caryophyllene (BCP) and the fact that it binds with the CB2 receptor of the mammalian endocannabinoid system—just as do cannabinoids. Some claim that the behavior of BCP is evidence of the validity of the entourage theory. All parties agree that more research is necessary to better understand this theory and the potential mechanisms involved in the interaction of terpenes and cannabinoids.


Conclusions

The study emphasized the need for additional research into the efficacy of terpenes in the human endocannabinoid system, including "more genotyping and sequencing studies...to encompass the full diversity of the [cannabis] species." It noted that Eurasian and African landrace cultivars of cannabis have been "under-sampled" and, therefore, warrant "special emphasis."


The study's authors reported that they consider cannabis to be a "useful system for terpene research" because it yields a significant volume of "diverse terpene-rich resin on [the] trichome-covered surfaces" of the mature flowers of female plants.


The study noted that, of the hundreds of terpenes and cannabinoids that have been identified in cannabis, "the biosynthesis of [fewer] than 30 has been characterized." It concluded that future research into cannabis terpenes "would benefit from a focused community effort to produce and archive a complete and reproducible set of metabolite and genomic data for one or a few genotypes that will serve as a reference framework."


The study recommended that the industry migrate away from a nomenclature involving "strains" ton one focused on varieties—but that this will require cooperation among cannabis breeders, cultivators, and researchers.

It explained that the goal of future scientific investigations should be to "establish reproducible cannabis varieties for use...in the industry, comparable to the well-defined grapevine varieties that are used in viticulture." The study also recommended that the industry migrate away from a nomenclature involving strains to one focused instead on varieties—but that this will require cooperation between cannabis breeders, cultivators, and researchers.


"To our knowledge, so far, no industry association has taken a lead to set community standards and practices or define community-accessible varieties," concluded the study.


View the original study.


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