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Phytocannabinoids

The cannabis plant is notable for its morphological variability and versatility as a foodstuff (seeds), fiber (stalks), and pharmaceutical (unfertilized flowering tops). There are many strains of cannabis derived from two primary species, Cannabis sativa and Cannabis indica.  

In 1753, Cannabis sativa was classified as a single species. Thirty-two years later, a second type of cannabis from India was identified. Its characteristics were sufficiently unlike Cannabis sativa to warrant a new species, so it was classified as Cannabis indica. To this day, sativa and indica are accepted as the two major subtypes of cannabis.  A third strain,  Cannabis ruderalis is a low-THC species  which is native to Central and Eastern Europe and Russia. It is widely debated as to whether or not ruderalis is a sub-species of Cannabis sativa. Many scholars accept Cannabis ruderalis as its own species due to its unique traits and phenotypes which distinguish it from Cannabis indica and Cannabis sativa.   

Due to observations that sativa and indica each possess unique characteristics and produce distinctive effects when consumed, it has been common to classify cannabis strains as one or the other. Many users of cannabis like to think of C. Sativa as producing a “head high” vs the “body high” of Cannabis indica. In more recent years, however, there have been a number of crossbreed strains, known as hybrids, that combine characteristics of both sativa and indica. Some hybrids approach a 50/50 mix, providing an all-over head/body high. Other hybrids lean one way or the other and could be classified as sativa-dominant or indica-dominant.

Given the wide variety of crossbreed strains, it is more accurate to abandon the “either-or” notion of sativas and indicas and rather to view them as two ends of a wide spectrum.  

Scholars in the field have proposed  an alternative nomenclature based on chemical varieties of cannabis plants (chemovars). Lewis et al., (2017) Pharmacological Foundations of Cannabis Chemovars Journal: Planta Med 10.1055/s-0043-122240 https://www.ncbi.nlm.nih.gov/pubmed/29161743

 

Cannabis can be divided into several categories based on cannabinoid content: Type I, THC-predominant is the most commonly used chemovar used in both medical and recreational settings.  Type II, contains both THC and CBD and  Type III is CBD-predominant.  High THC and high-myrcene chemovars appear to dominate the market now. However Type II and Type III Cannabis cheomars that display CBD and terpenoid-rich profiiesl have the capacity to improve both the efficacy aof THC and minimize adverse evetns associated with it. 

 

Cannabis is known to contain over 100 related molecules, the phytocannabinoids and greater than 200 terpenoids.  What purpose these molecules serve for the plant itself is not really understood.  Phytocannabinoids are seen by some researchers as by-products of intermediary metabolism with no specific function in the plant.  However, some phytocannabinoids are mildly anti-fungal and others may serve to repel destructive insects and to attract others (e.g., to lure bees for cross-pollination). Some cannabinoids may possess physiological properties involved in the regulation of plant growth and sexual development.

In contrast to the paucity of information regarding the function of cannabinoids in plants, the actions of phyto-cannabinoids in the human brain are much better understood. Δ9-Tetrahydrocannabinol (THC) was isolated in 1963 and its metabolism in rodents and humans was elucidated, including its hydroxylation to an active metabolite and further oxidation to an inactive acid which then binds to a sugar molecule. The acid-derived metabolites are stored in lipid-rich tissues and are slowly released. Hence, the major final THC metabolite can be detected in human urine for several weeks after cannabis use.  Administration of Δ9-THC (orally, intravenously or inhaled in smoke), results in psychological changes similar to those reportedly experienced in response to recreationally consumed plant material.  A synthetic analog of Δ9-THC, nabilone (Cesamet: Valeant Pharm North America) was approved by FDA in 1981 to suppress nausea and vomiting associated with chemotherapy .   Synthetic Δ9- THC dronabinol (Marinol; Solvay Pharmaceuticals, Inc) was approved as an anti-emetic in 1985 and subsequently as an appetite enhancer in 1992.  For an excellent summary chart prepared for Canadian prescribers of cannabinoid see: http://www.rxfiles.ca/rxfiles/uploads/documents/Pain-QandA-cannabinoids.pdf