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Deep Dive: State of the Art of Cannabis in 2023

This 1,800-word homework assignment from Higher Learning LV's upcoming Cannabis Foundation course offers a glimpse of what students of this training can expect. This ad-free article will be online until January 28, after which it will be available only to students enrolled in Cannabis Foundation.

 

A March 2023 study entitled "Cannabis—A State of the Art about the Millenary Plant: Part I" that was published in the journal Forensic Chemistry investigated "information related to general concepts of Cannabis, such as its composition, taxonomic classification, and a summary of the biosynthesis of its main constituent class (cannabinoids)...about this millenary plant."


This detailed scientific investigation leveraged the most recent data to provide a comprehensive overview of the history, chemistry, anatomy, and medical applications of cannabis, with a focus on important milestone discoveries during the past century.


History of Cannabis

This comprehensive study report provided a detailed history of the use of cannabis and the most significant research studies regarding its chemical constituents. Of note are the discoveries made during the 20th century, including those by legendary cannabinoid researcher Dr. Raphael Mechoulam.

Dr. Raphael Mechoulam


"Its millenary history, guided by evolutions, discoveries, and new applications, began millennia BCE recorded in archaeological evidence discovered in Central Asia, which indicates the cultivation of this plant for use as fiber and rope around 12,000 BCE and due to hemp tissue artifacts dating several millennia ago, which were discovered in China," reported the research.


The study explained that the botanical classification and naming of Cannabis did not begin until the late 18th century. It reported that "the international community recognizes the year 1753 as the starting point for the modern nomenclature botany of this plant, when the first official publication using the scientific denomination of species, Latin binomials is Linnaeus’s Species Plantarum, Cannabis sativa."



The researchers reported that there are currently 600 commercially available varieties of cannabis but that there is "no general agreement on the taxonomic classification of this plant." The study noted "historical contributions and therapeutic directions" regarding cannabis and cannabinoids, including:

  1. 1896: Cannabinol (CBN) first named.

  2. 1940: Cannabidiol (CBD) isolated and correct structure of CBN determined by Roger Adams.

  3. 1942: Delta-9 THC first isolated.

  4. 1963: Correct molecular structure of cannabidiol (CBD) first identified by Mechoulam and Shvo.

  5. 1964: Gaoni and Mechoulam first to isolate cannabigerol (CBG); first reported correct molecular structure of delta-9 THC.

  6. 1964: Cannabicyclol (CBL) first detected (first named cannabipinol).

  7. 1966: Cannabichromene (CBC) first disclosed by two independent research teams (one being Gaoni and Mechoulam).

  8. 1966: Cannabitriol (CBT) reported by Japanese researchers Obata and Ishikawa.

  9. 1966: Delta-8 THC isolated by Hivey et al.

  10. 1967: Gaoni and Mechoulam propose name "cannabicyclol" to replace "cannabipinol" for CBL.

  11. 1973: Cannabielsion (CBE) detected by Bercht et al.

  12. 1976: Chemical structure of CBT elucidated by Chan et al.

  13. 1977: Cannabinodiol (CBND) isolated by Lousberg et al.


Trichomes Do the Work

The study identified the source of nearly all terpenes and cannabinoids produced by the plant, trichomes. It identified three types of glandular trichomes (the variety that produces molecules like CBD, THC, and alpha-pinene) and multiple types of non-glandular trichomes,

Image courtesy Darryl Glubczynski


Reported the study: "Particularly in glandular trichomes, Cannabis resin is produced and stored. These are associated with the plant's flower structures, which are also able to be found in the lower regions of the leaves and stems. However, it is the combination of different trichomes that enables positive identification of even fragmented material from the Cannabis plant."


One vs. Three Species

The study explained that the issue of the number of species in cannabis has been widely debated, but that modern consensus is that it is a single species with a relatively wide range of varieties—and that these varieties are not separate species by the strict scientific definition of the term.


"The number of species in cannabis has been widely debated, but modern consensus is that it is a single species with a relatively wide range of varieties."

The present study noted a 1974 scientific investigation that "distinguished three species within the Cannabis genus: Sativa L., indica Lam. and ruderalis." This has obviously led to many citations over the decades, giving well-respected industry professionals and wellness practitioners the belief that cannabis is three distinct species.


While opinions fall on both sides of the issue, the study reported that "it is currently commonly accepted that the Cannabis plant is monotypic and the other [so-called] species are recognized as varieties of Cannabis sativa L."


Constituents of Cannabis

The study reported that the primary constituents of cannabis are cannabinoids, delta-9 THC, flavonoids, and terpenoids (which includes terpenes and terpene-like molecules, including "alcohols, ethers, aldehydes, ketones, and esters").


Cannabinoids & Cannabinoid Subclasses

The study identified and listed 120 cannabinoids, including 23 delta-9 THC types, five delta-8 THC varieties, 16 CBG types, nine CBC types, seven CBD types, two CBND varieties, five variants of CBE, three types of CBL, 11 types of CBN, nine varieties of CBT, and 30 "miscellaneous" cannabinoids that did not fit a group category.


The study listed 120 cannabinoids, including subclass types, including delta-9 THC types, delta-8 THC varieties, CBG types, CBC types, CBD types, and varieties of CBND, CBE, CBL, CBT, "miscellaneous."

The research report explained that cannabinoids begin their lives as acids, or acidic precursors, that under the right environmental conditions—namely the application of UV light and heat—transmogrify into their neutral (sometimes called "active") and more known siblings. Thus, CBDA turns into CBD with the application of heat during the chemical process of decarboxylation. Likewise, THCA when decarboxylated morphs into THC.


The study identified 11 chemical categories, or what it called "subclasses" of cannabinoids produced by hemp and cannabis, including the following:

  1. Δ9- tetrahydrocannabinol (Δ9-THC)

  2. Δ8-tetrahydrocannabinol (Δ8-THC)

  3. Cannabigerol (CBG)

  4. Cannabichromene (CBC)

  5. Cannabidiol (CBD)

  6. Cannabinodiol (CBND)

  7. Cannabielsoin (CBE)

  8. Cannabicyclol (CBL)

  9. Cannabinol (CBN)

  10. Cannabitriol (CBT)

  11. Miscellaneous-type

The study reported that the most abundant cannabinoids produced by cannabis are delta-9 THC, CBD, CBG, CBN, and CBC.

It should be noted that the acidic precursor of the delta-9 subclass, THCA, conveys no psychoactivity when consumed by humans or mammals. It's downstream (post-decarboxylation) chemical cousin THC, however, is strongly psychoactive. This is a good example of how small modifications in the molecular structure of a cannabinoid can result in a change in what scientists call its binding affinity with specialized CB1 and CB2 receptors in the ECS. A small molecular modification makes all the difference between a cannabinoid with no psychoactivity (THCA) and one that conveys heavy psychotropic effects (THC).


It is also important for students to understand that delta-9 THC is not the only psychoactive cannabinoid produced by the herb. Delta-8, delta-10, HHC, THC-O Acetate, THCV, and CBN are all mildly to strongly psychoactive.


Delta-9 THC

The researchers reported that delta-9 THC is "considered the main psychoactive compound of the Cannabis plant.' They noted that all parts of the cannabis plant produce delta-9 THC, including the flowers (which are 10-12 percent delta-9 THC), leaves (1-2 percent THC), stems (0.1-0.3 percent THC), and roots (below 0.03 percent THC).


The study reported that, in seeds, "the presence of Δ9-THC is a debatable topic among researchers." It noted how a 2007 study reported that cannabis seeds may contain 0.5 µg/g (micrograms, or one millionth of a gram) (depending on plant variety). However, in 2009, the United Nations Office on Drugs and Crime reported that cannabis seeds contain zero delta-9 THC and attributed studies that have indicated the presence of THC in seeds to the "likely contamination with Cannabis materials (e.g., flowering tops, husks, resin), resulting in detectable amounts of Δ9-THC."


"The study explained how, in fresh plant material (biomass), roughly 95 percent of delta-9 THC consists of its precursor, THCA."

A more recent 2018 study "detected Δ9-THC and its precursor acid Δ9-THCA, in addition to other cannabinoids, by high-resolution mass spectrometry by Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry."


The study explained how, in fresh plant material (biomass), roughly 95 percent of delta-9 THC consists of its precursor, THCA (converted to THC during decarboxylation). It explained that THC and other cannabinoids "have been explored as pharmaceutical targets with possible applications in the treatment of symptoms and diseases such as pain, inflammation, emesis, anorexia, multiple sclerosis, neurodegenerative disorders, epilepsy, cancer, cardiovascular disorders among others, although, historically, the use of Cannabis for medicinal purposes dates back millennia."


Flavonoids

The study described a family of chemical compounds other than terpenes and cannabinoids called flavonoids "that are believed to contribute to the medicinal versatility [of cannabis]." It described how more than 20 flavonoids have been discovered to be produced by some cultivars of cannabis and hemp.


These specialized molecules perform a number of functions, chief among them being providing pigment and coloration to the plants that produce them. These colors act as a siren song to pollinators like humans and insects, similarly to how terpenes attract cultivators and pollinating insects via aroma. In the same manner, flavonoids and terpenes also use pigment and scent in an attempt to thwart pests and predators with an offensive or alerting fragrance in an evolutionary effort to preserve and propagate the species.


The flavonoids found in cannabis and hemp include apigenin, kaempferol, quercetin, and luteolin, all of which—like terpenes—are produced a variety of botanical species other than cannabis. However, three flavonoids are specific to cannabis and are appropriately named cannflavins (not cannaflavins, a common misspelling). These include cannflavin A, cannflavin B, and cannflavin C.


"Three flavonoids that are specific to cannabis and that are appropriately named cannflavins (not cannaflavins, a common misspelling) include cannflavin A, cannflavin B, and cannflavin C."

This study reported that the production of flavonoids, including the exact types manufactured and their volumes, is dependent upon environmental factors. For example, the research noted that cannflavin A is produced in response to solar radiation, temperature, humidity, and rain. Other environmental conditions that might trigger production of flavonoids are biotic and abiotic stresses.


"The identity of additional flavonoids, particularly those unique to Cannabis, can facilitate a comprehensive understanding of the biosynthesis and functions of flavonoids in this important plant," reported the study's authors.


The research reported that other studies has identified "promising anti-inflammatory therapeutic action" in flavonoids that is "about 30 times more effective than aspirin in inhibiting prostaglandin E2 release when assayed in human rheumatoid cells."


The researchers identified a possible biosynthetic pathway (also called a reaction sequence) for the production of cannflavin A and cannflavin B: Luteolin > chrysoeriol > cannflavin A and cannflavin B.


Terpenes

The study's authors reported that more than 100 different terpenes have been discovered in cannabis and hemp, including "monoterpenes, sesquiterpenoids, triterpenes, diterpene, and terpenoid derivative." Terpenes are among the aromatic molecules responsible for the sometimes pungent aroma of marijuana, most of which have been found to deliver medicinal efficacy in the form of things such as reduced inflammation, lower anxiety, improvements for depression, and even the shrinkage of tumors in cancer patients.


"Terpenes are among the aromatic molecules responsible for the sometimes pungent aroma of marijuana, most of which have been found to deliver medicinal efficacy."

Within the plants that produce them, terpenes "can be involved in respiration, photosynthesis, and secondary metabolites that participate in communication and plant defense mechanisms."


Conclusions

The study concluded that it documented the current "state of the art...leading concepts for understanding and the evolutionary line of research on the Cannabis plant over the years until its current applications."


As such, the study included the most recent data and previous research findings regarding the history, morphology, taxonomy, phytochemistry, cannabinoid classes, and contributions in medicine. "Thus, all these important and cooperative notes mentioned above show the breadth of the theme and its applicability in various areas of science," summarized the study's authors.


View the original study.



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