The Four Pillars of Cannabis Science

Updated: May 30

Welcome to the Higher Learning LV Knowledgebase. This collection of highly educational articles and videos is designed specifically for professionals within the cannabis and hemp industries.


In our weekly C3 Twitter Spaces, host Curt Robbins often mentions the Four Pillars of cannabis science: Cannabinoids, terpenes, flavonoids, and the endocannabinoid system. Below, we define these terms for those who are new to this area of study or have been recently hired by a cannabis or hemp company.

This free article is an excerpt from the forthcoming Higher Learning LV course Understanding Cannabis.


Pillar 1: Cannabinoids

Cannabinoids are the special molecules that, as their name implies, are produced only by cannabis (and hemp). The most common and heavily marketed cannabinoids in the United States are cannabidiol (CBD) and tetrahydrocannabinol (THC).


Decades of peer-reviewed scientific research studies have revealed that many cannabinoids, in some use cases, may deliver wellness efficacy that includes potential reductions in inflammation, anxiety, and depression and perhaps the ability to combat certain types of serious diseases, including arthritis, cancer, multiple sclerosis, migraine headaches, fibromyalgia, autism, childhood epilepsy, and a variety of other conditions (particularly those based in inflammation).


Analogs, Acidic Precursors, & Varins

A common confusion among those new to the cannabis industry is the various molecular isomers, or analogs, of each cannabinoid. For example, CBD features several different versions of this popular botanically sourced wellness molecule, a few of which are listed below:

  • CBDA: The acidic precursor that produces CBD

  • CBD: What scientists call the neutral version of this molecule

  • CBDV: The varin version

  • CBDVA: The acidic precursor that produces CBDV

Likewise, THC features a set of isomers that includes:

  • THCA: The acidic precursor that produces THC

  • THC: The neutral version (delta-9)

  • THCV: The varin version

  • THCVA: The acidic precursor that produces THCV


Other cannabinoids, including CBG, CBN, and CBC feature similar sets of analog molecules (including CBCV). It should be noted that these isomers sometimes deliver not merely different efficacy, but polar opposite results.


For example, THC is infamous for increasing appetite (the colloquial "munchies"), a beneficial characteristic for patients undergoing chemotherapy and pregnant women suffering nausea. However, THCV, the varin version of THC, does the opposite and decreases appetite (as do certain terpenes, which are explained below). This makes these cannabinoids of potential value to patients suffering obesity and Type 2 diabetes.


Roughly 150 different cannabinoids are produced by the cannabis plant species. However, it should be noted that not all 150 manifest in an individual plant. A small subset of this number are produced.

Roughly 150 different cannabinoids have been isolated that are produced by the cannabis plant species. However, it should be noted that not all 150 manifest in an individual plant. A small subset of this number actually appears.


To learn more about cannabinoids, follow us on social media and watch for the upcoming release of our new course Understanding Cannabis.


Pillar 2: Terpenes

Terpenes are flavor and aroma molecules that give particular strains of cannabis their infamous fragrances. They are one of the most common types of molecules on earth and are produced by tens of thousands of plant species beyond cannabis.

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Unlike cannabinoids, no terpene is exclusive to cannabis. In other words, the roughly 200 terpenes produced by various strains of cannabis and hemp are also produced by thousands of other plant species. In fact, approximately 20,000 plant species manufacture more than 40,000 varieties of terpenes. One study indicated that there may be more than 70,000 different terpenes in nature!


Just as with cannabinoids, an individual plant will not produce all 200 terpenes programmed into the cannabis DNA. Instead, a relatively small subset will present itself, typically dominated by a set of two or three terpenes (recent research that analyzed 90,000 loose-leaf cannabis samples identified common pairs of terpenes).


From an evolutionary perspective, the function of terpenes is the protection and propagation of the plant species that produce then. This is accomplished by dissuading pests and predators (which find their aroma or taste to be repulsive) while simultaneously attracting cultivators and pollinators (humans and insects that find their smell and flavor to be pleasing) in an elaborate siren song designed simply to help the species survive.


Unlike cannabinoids, no terpene is exclusive to cannabis. In other words, all terpenes found in cannabis are also produced by a number of other plant species. Roughly 20,000 plant species manufacture more than 40,000 varieties of terpenes.

The most common terpene in nature is pinene, with limonene running in second place. In the cannabis plant, the most common terpenes are myrcene, beta-caryophyllene (BCP), and humulene. Humulene is also produced by the hops used to brew beer, which are an ancient botanical cousin to cannabis. In fact, the two plant species make many of the same terpenes.


Just as cannabinoids feature a number of analogs of their neutral versions, terpenes often appear in what are called stereo isomer pairs. This means that the two molecules are very similar in terms of structure and weight, with only minor differences. An example is alpha-pinene and beta-pinene. However, the minor chemical differences of terpene pairs are significant enough to change their behavior in the human body and result in not only different aromas, but also varying medicinal efficacy.


To learn more about terpenes, follow us on social media and watch for the upcoming release of Understanding Cannabis.


Pillar 3: Flavonoids

Flavonoids serve an identical evolutionary function as that of terpenes: Attracting pollinators and repulsing pests and predators in an effort to help the species survive. While terpenes accomplish this function via aroma and flavor, flavonoids do so with pigment.

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Flavonoids are commonly misinterpreted to be flavor agents (a role played by terpenes and cousin molecules such as acetates, esters, and ketones). Actually, the Latin root of the term, flavus, means yellow; classical interpretations sometimes describe a pale yellow organic pigment. Flavonoid experiments were first documented in 1664 by Robert Boyle in his book Experiments and Considerations Touching Colours. The first flavonoid was identified by Albert Szent-Györgyi, a Hungarian biochemist, in 1930.


Flavonoids are a diverse group of plant chemicals found in a large number of flowers, fruits, and vegetables. These special compounds are responsible for the sometimes vivid colors of the plants that produce them.

Flavonoids are a diverse group of plant chemicals found in a large number of flowers, fruits, and vegetables. These special compounds are responsible for the sometimes vivid colors of the plants that produce them. Perhaps of greater value to humans, peer-reviewed research studies indicate that flavonoids may deliver medicinal efficacy—most notably anticancer and anti-inflammatory benefits.


Interestingly, flavonoids are also responsible for the colorful wings of butterflies. Because butterflies do not manufacture their own pigment molecules, they absorb them from the plants they eat.


Cannflavins

While cannabinoids are exclusive to the cannabis plant species (no other species produces them) and no terpene is exclusive to cannabis, flavonoids are a hybrid of these two models. Of the roughly 20 flavonoids programmed into the cannabis genome (DNA), about three are exclusive to cannabis.


While cannabinoids are exclusive to the cannabis plant species (no other species produces them) and no terpene is exclusive to cannabis, flavonoids are a hybrid of these two models.

Called cannflavins, these chemical compounds have been found to deliver significant health benefits, including reductions in inflammation and anticancer efficacy. The most researched cannflavins include cannflavin A, cannflavin B, and cannflavin C.


To learn more about flavonoids, follow us on social media to get notices for when the Higher Learning LV course Understanding Cannabis is released.


Pillar 4: Endocannabinoid System

Pillar 4 is special because it is the body-wide system of neurotransmitters and microscopic cellular receptors that binds with or otherwise interacts with the first three pillars. The endocannabinoid system (ECS) was discovered fairly recently, in the early 1990s, in Israel by Dr. Raphael Mechoulam (learn from our exclusive interview with Mechoulam).


Research studies have determined that the ECS may play an important role in the human immune system and overall health and wellness, including energy levels, metabolism and sleep, sexual function, cognition, mood, and the ability to fight off disease.

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The ECS may also play a special role in common conditions like depression and pain. Additional research has shown a potential ECS role in the body's defense against diseases such as cancer.


The ECS internally produces its own cannabinoids called endocannabinoids. These include anandamide and 2-AG. Research has revealed that major plant-based cannabinoids such as CBD and THC are mimetic, meaning that they mirror the behavior (and cellular binding characteristics) of the major endocannabinoids anandamide and 2-AG.


Some theorize that humans who feature an ECS that is deficient or unhealthy and that does not produce enough of these endocannabinoids may gain benefit from supplementation by botanically sourced phytocannabinoids like CBD, THC, and CBG.

Some theorize that humans who feature an ECS that is unhealthy and that does not produce enough of these endocannabinoids may gain benefit from supplementation by botanically sourced phytocannabinoids like CBD, THC, and CBG.


To learn more about Higher Learning LV's Four Pillars of cannabis science, stay tuned for our forthcoming Understanding Cannabis course. This on-demand course will be followed by the courses Understanding Cannabinoids, Understanding Terpenes, and Understanding Flavonoids—all developed exclusively for busy industry professionals.


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