CBD: We know it comes from cannabis, but how and why is it made?
Written by: Dr. Jonny Lisano, Ph.D.
In this article, we will discuss the basic physiology behind the making of cannabidiol (CBD) and some theorized reasons why plants of the cannabis family, like hemp and marijuana, might produce phytocannabinoids like CBD.
How does Cannabis Sativa L. Produce CBD?
When referring to products within the cannabis industry, particularly those containing cannabidiol (CBD), we typically classify them as being either hemp or marijuana-derived. Recent evidence suggests that there are distinct genetic differences between hemp and marijuana (Sawler 2015), but due to generations of select cultivation and crossbreeding there is not enough of a difference to classify them as different plants. Currently, both hemp and marijuana are classified as the same plant Cannabis Sativa L., because of this, the only clear distinction between hemp and marijuana is that based on legality.
Hemp, of course, is classified within the United States as having less than 0.3% delta-9-tetrahydrocannabinol (THC) and anything with more than 0.3% THC is classified as marijuana. The reason hemp and marijuana are so sought after is for their production of the compounds known as phytocannabinoids, or more commonly referred to as cannabinoids. Hemp is sought after for its high CBD content, while marijuana is most desired for its high production of THC. The endocannabinoid system, on which these compounds act, is actually so named because it was first discovered through receptors in the central nervous system interacting with THC.
Cannabidiol, also known more commonly as CBD, is one of more than 100 identified phytocannabinoids produced by the cannabis plant Cannabis Sativa L. (Russo 2011). The majority of the active components in cannabis products are produced in structures called trichomes in the plant (Russo 2011). In these trichomes, the first step in producing CBD is the creation of cannabigerolic-acid (CBGA) (Thomas 2016). The cannabinoid CBGA is a precursor to the formation of multiple cannabinoids, including CBD, THC, cannabichromene (CBC) and cannabigerol (CBG) (Thomas 2016). The formation of CBGA begins with building blocks of Coenzyme A and a fatty acid. The use of fatty acids in the production of cannabinoids is a primary reason why cannabinoids like CBD are fat-soluble. Following multiple intermediate steps, CBGA is eventually derived from olivetolic acid and geranyl pyrophosphate (Thomas 2016). Side note: the “ger” in cannabigerolic-acid comes from the “ger” in geranyl pyrophosphate.
As stated previously, CBGA can then be used for the eventual formation of CBD. First, CBGA is converted to the acidic form of CBD, cannabidiolic acid (CBDA). This process is performed by CBDA synthase (Taura 2007, Thomas 2016). However, the cannabinoid CBDA is not yet the CBD that we all know and love. For CBD to be produced the next step that must occur is the chemical decarboxylation of CBDA. For those of you not well versed in the terminology of chemistry, decarboxylation simply refers to the removal of CO2 from CBDA. Once this CO2 is removed, which is typically done through the use of heat, CBD has now been formed (Hartsel 2016). It would make sense then that CBD, does not naturally occur in abundantly high quantities of either marijuana or hemp, but rather is found as the precursor CBDA. This is why the cannabis industry has developed effective ways, like supercritical CO2 extraction, to efficiently extract and decarboxylate cannabinoids like CBD in highly concentrated quantities.
The CBD synthesis process within cannabis can be seen in the figure below in it’s entirety.
Why does Cannabis Sativa L. produce cannabinoids like CBD?
There are mixed schools of thought on why Cannabis Sativa L. produces cannabinoids. One thought is that the cannabis plant produces the active components as a natural defense mechanism against parasites pests and potential predators. However, many of the insects that would threaten the plant are devoid of an endocannabinoid system, and thus would be immune to any potential negative effects. Another school of thought is that Cannabis Sativa L. produces these cannabinoids to prevent mammalian herbivores and omnivores from eating it; however, while these mammals do possess an endocannabinoid system, cannabinoids in their raw, acidic form are not physiologically active. Thus, similarly to insects, these mammals would not feel any effects from these cannabinoids and would have no reason to be deterred from eating the plant. So why then does cannabis produce these cannabinoids?
If you were to say that cannabinoids are produced by the cannabis plant to appease us, the “human overlords”. Well, you might actually be right… among biologists studying the Cannabis Sativa L. plant itself, this is one of the more popular theories. The relationship between humans and cannabis has existed for thousands of years (Sawler 2015). This has spurred the formation of a symbiotic relationship between humans and the plant. Humans grow and cultivate cannabis for its therapeutic effects, ensuring the survival of the cannabis plant at the same time. Scientists believe that due to the longterm cultivation and selective breeding of the Cannabis Sativa L. plant, we have naturally encouraged the plant to produce more cannabinoids over time, through the increased gene expression of the enzymes necessary to create the cannabinoids like CBD, THC, and CBGA. Inadvertently because of these generations of selective breeding for high cannabinoid content scientists are still unsure as to why the cannabis plant produces cannabinoids.
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