Biosynthesis Pathway of Phytocannabinoids: THC and CBD

Cannabinoids are a class of lipophilic molecules that interact with the endocannabinoid system (ECS) of the human body. These molecules can be further characterized into two main categories: phytocannabinoids and endocannabinoids. Phytocannabinoids are cannabinoids that are produced by plants and endocannabinoids are produced my mammals. Before we dive into the world of phytocannabinoids and how they work, lets first explore why mammals produce endocannabinoids. In short, two proteins in the brain called CB1 and CB2 respond to endocannabinoids produced naturally in the body to regulate a myriad of physiological processes including mood, appetite and immunity.  Cannabinoids such as the known Tetrahydrocannabinol (Δ9-THC) and Cannabinol (CBD) are considered “phytocannabinoids” because they are produced in the glandular trichomes of the cannabis plant. Recently, it has been discovered that Cannabis plants are not the only plant species to produce phytocannabinoids. 

Phytocannabinoids: Origin

Phytocannabinoids are produced in flowering plants, liverworts and fungi (Radula sp.). However, these compounds were first isolated and discovered in Cannabis sativa L (Cannabaceae) in 1940. There are has been over 113 cannabinoids discovered and classified thus far.  

So unlike endocannabinoids and phytocannabinoids that have certain affects to the mammalian body, why do plants produce them? In theory from an evolutionary standpoint, if plants are still producing them, it must have some sort of beneficial affect to the plant itself. Studies have supported this idea showing that phytocannabinoids are protecting the plant from UV radiation and specifically, the THC-A (inactive form of THC) and CBGA (the precursor) have insecticidal properties. 

Biosynthesis Pathway of THC and CBD

The definition of a biosynthesis pathway is a series of chemical reactions facilitated by specific enzymes to create complex molecules from simpler ones. As of date, the biosynthesis pathway of cannabinoids in Cannabis has fully been elucidated and the pathways in Rhododendron and Radula species are still yet to be studied. There are several different components of the THC and CBD biosynthesis pathway that make it complex. Firstly, the three main enzymes involved are CBDA synthase, CBCA synthase and THCA synthase. These enzymes are involved in the conversion of the precursors CBGVA and CBGA into CBDA, THCA and CBCA. 

Pathways to remember ( = changes to): 

CBDA  CBNA or CBEA

CBCA CBLA

THCA CBNA or Δ8-THC

It is important to note, that cannabis plants produce the inactive form CBDA and THCA and not the cannabinoids THC and CBD that are recognized by our endocannabinoid system. So…the final products of the cannabinoid biosynthesis pathway within the plant are THCA and CBDA. THCA and CBDA are only converted to THC and CBD respectively following exposure to heat (a.k.a when smoked or undergone a heating procedure).  This heating process in which THCA and CBDA loses the carboxyl group to make the active form is called decarboxylation. 

Asrinus Subha is plant geneticist with many years of R&D experience in the cannabis industry. She can provide in-depth knowledge of basic scientific principles in the fields of cell and systems biology and cannabis science. Visit her website: www.writewithme.ca & follow her on Instagram @thepinkbotanist and also onTwitter @AsrinusSubha for many cannabis stories.