www.idosr.org Moore ©IDOSR PUBLICATIONS International Digital Organization for Scientific Research ISSN: 2579-0811 IDOSR JOURNAL OF BIOCHEMISTRY, BIOTECHNOLOGY AND ALLIED FIELDS 5(1): 39-44, 2020.

An Overview of the Phytochemistry of Cannabis sativa L.

Ethan Moore

Environmental Biology, York University Toronto, Canada.

ABSTRACT Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of textile fiber since the dawn of times. This fast-growing plant has recently seen a resurgence of interest because of its multi-purpose applications; it is indeed a treasure trove of phytochemicals and a rich source of both cellulosic and woody fibers. Equally highly interested in this plant are the pharmaceutical and construction sectors, since its metabolites show potent bioactivities on human health and its outer and inner stem tissues can be used to make bioplastics and concrete-like material, respectively. Phytocannabinoids are terpenophenolic secondary metabolites predominantly produced in Cannabis sativa L. The principal active constituent is ∆9- (THC), which binds to endocannabinoid. represent the most studied group of compounds, mainly due to their wide range of pharmaceutical effects in humans, including psychotropic activities. The therapeutic and commercial interests of some terpenes and phenolic compounds, and in particular stilbenoids and lignans, are also highlighted in view of the most recent literature data. In this review, the rich spectrum of hemp phytochemicals possess by Cannabis is discussed with a view to highlighting them and their importance. Keywords: Cannabis, Lignin, Cannabinoids, Terpenes, Lignans, Phytochemical profile.

INTRODUCTION The concept of Cannabis as a monotypic is a lax panicle or compound cyme genus containing just a single highly composed of many individual, yellowish polymorphic species is widely accepted, green, pedicellate flowers containing five although there has been a long-standing pendulous anthers. The pistillate flowers debate among taxonomists regarding are green, sometimes purple to red, classification of the existing varieties. sessile, grouped in apical leaf axils or Other previously described species, terminals of branches. including C. indica Lam. and C. ruderalis It has a long history of medical use in the Janisch., are now recognised as varieties Middle East and Asia, dating back to the of C. sativa L. based on morphological, sixth century BC. During a period of anatomical, phytochemical and genetic colonial expansion in the early nineteenth studies [1] [2]. Cannabis sativa L. century, cannabis found a way to Western (Cannabaceae) is one of the first plants Europe as a medicine to alleviate a variety cultivated by man and one of the oldest of conditions, such as pain, spasms, plant sources of fibre, food and remedies. dysentery, depression, sleep disturbance C. sativa L. is an annual, herbaceous, and loss of appetite. In the beginning of taprooted and predominantly dioecious the twentieth century, due to the plant. Its height (0.2–6 m) and degree of availability of substitute drugs, absence branching depend on both genetic and of quality control and the risk of abuse environmental factors. Staminate (male) and intoxication, cannabis medication fell plants are usually taller but less robust into disuse. Phytochemical analysis of than pistillate (female) plants. The leaves cannabis in the 1940s and 1960s led to are petiolate, palmately compound, with the discovery of a unique group of an odd number [3] [4] of coarsely serrate, terpenophenolic secondary metabolites, lanceolate leaflets. The male inflorescence known as cannabinoids, of which

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www.idosr.org Moore trans−∆9-tetrahydrocannabinol (THC) was Phytochemical profile shown to be the primary active The term cannabinoids is used for a constituent which is responsible for the number of chemicals found in the plant’s psychoactive effect [5]. Many extracts of Cannabis sativa. Cannabis natural products besides cannabinoids sativa produces unique secondary have been isolated from cannabis, metabolites consisting of alkyl resorcinol including terpenes, flavonoids, steroids and monoterpene groups. The plant and nitrogenous compounds. Up to date, Cannabis sativa contains more than 60 750 constituents have been identified terpenophenolic compounds, named from cannabis, out of which over 100 are phytocannabinoids. The best studied classified as cannabinoids [6]. phytocannabinoid is Δ9- Cannabis (Cannabis sativa, or hemp) and tetrahydrocannabinol (TCH) which binds its constituents-in particular the specific G-protein-coupled receptors cannabinoids, have been the focus of named (CB1 and CB2) extensive chemical and biological receptors, it is the main active component research for almost half a century since which has been shown to induce acute the discovery of the chemical structure of transient psychotic reactions in its major active constituent, Δ9- previously well individuals when tetrahydrocannabinol (Δ9-THC). The administered as an isolated compound plant's behavioral and psychotropic [8]. effects are attributed to its content of this Δ9- tetrahydrocannabinolic acid (THCA), a class of compounds, the cannabinoids, product of the cannabinoid class, is the primarily Δ9-THC, which is produced primary psychoactive agent. This mainly in the leaves and flower buds of compound is produced as an acid in the the plant. Besides Δ9-THC, there are also glandular trichomes of inflorescence non-psychoactive cannabinoids with bracts and undergoes decarboxylation several medicinal functions, such as with age or heating to Δ9- cannabidiol (CBD), cannabichromene tetrahydrocannabinol (THC) [9] [10]. Still (CBC), and cannabigerol (CBG), along with there are other components in this other non-cannabinoid constituents chemical mixture, such as cannabidiol belonging to diverse classes of natural (CBD) and cannabigerol, which may also products. Today, more than 560 play a role in modulating the effects of constituents have been identified in TCH [11]. A number of cannabis cannabis [7]. The recent discoveries of the components that do not activate the medicinal properties of cannabis and the receptors are often called cannabinoids. cannabinoids in addition to their potential Phytocannabinoids applications in the treatment of a number Phytocannabinoids represent a group of of serious illnesses, such as glaucoma, C21 or C22 (for the carboxylated forms) depression, neuralgia, multiple sclerosis, terpenophenolic compounds Alzheimer's, and alleviation of symptoms predominantly produced in Cannabis. of HIV/AIDS and cancer, have given More than 90 different cannabinoids have momentum to the quest for further been reported in the literature, although understanding the phytochemistry of this some of these are break down products plant. This review presents an overview of [12]; [13]; [14]; [15] and they are generally phytochemical constituents of cannabis classified into 10 subclasses and its chemical constituents. Particular (Brenneisen,2007). Cannabis may contain emphasis is placed on the newly- over 60 classical cannabinoid (tricyclic identified/isolated compounds. In dibenzopyran) compounds and some, addition, techniques for isolation of such as cannabidiol, may modulate the cannabis constituents and analytical response to THC. Cannabinoids methods used for qualitative and (cannabigerol (CBG), cannabichromene quantitative analysis of cannabis and its (CBC), cannabidiol (CBD), cannabicyclol products are also reviewed. (CBL), cannabielsoin (CBE), cannabinol (CBN), cannabinodiol (CBND), cannabitriol

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www.idosr.org Moore (CBT)) nitrogenous compounds, amino and β-pinene, terpinolene and linalool. acids, proteins, enzymes, glycoproteins, Sesquiterpenes, and β-caryophyllene and sugars, hydrocarbons, simple alcohols, α- humulene in particular, occur also to a simple aldehydes, simple ketones, simple large extent in Cannabis extracts. acids, fatty acids, simple esters, lactones, Terpenes, along with cannabinoids, have steroids, terpenes, non-cannabinoid successfully been used as phenols, flavonoids, vitamins, pigments chemotaxonomic markers in Cannabis, as and elements are the chemical classes they are both considered as the main compounds of Cannabis sativa which has physiologically active secondary been identified [16] [17]. metabolites [26]. When grown in Δ9-tetrahydrocannabinol (TCH) standardized conditions, a significant and The cannabis plant (Cannabis sativa) positive correlation was found between contains many compounds, but Δ9- the level of terpenes and cannabinoids tetrahydrocannabinol (THC) is the main [2]. This may be explained by the fact that psychoactive ingredient. THC breaks mono- and sesquiterpenes are down to produce cannabinol and was synthesized in the same glandular identified along with cannabidiol (the trichomes in which the cannabinoids are main non-psychoactive component) [18] produced [5]. This association was, [19]. However, THC was not isolated, however, not confirmed on a larger panel synthesized, and stereochemically of samples coming from different origins defined until the 1960s [20]. THC is [12]. concentrated in the flowering head of the Cannabidiol (CBD) female plant and selective growing in the Cannabidiol was isolated in 1940 [18] and past 5– 10 years has substantially its absolute configuration established by increased THC content from 1-3% THC in synthesis of (-)-CBD as (-)-trans-(1R, 6R) the “flowerpower” era to 6–13% and [19]. The optical rotation of above. cannabidivarin was reported as [α] D- Terpenes 139.5-(chloroform) [20]. All of the known Terpenes form the largest group of CBD-type cannabinoids have trans-(1R, phytochemicals, with more than 100 6R) absolute configuration and molecules identified in Cannabis [21] [22]. presumably also negative optical rotation. Terpenes are responsible for the odor and Phenolic Compounds flavor of the different Cannabis strains. Phenolic compounds, also known as They have therefore likely contributed to phenylpropanoids, constitute one of the the selection of Cannabis narcotic strains most widely distributed group of under human domestication [23]. secondary metabolites in the plant Terpenes are classified in diverse families kingdom. They present more than 10,000 according to the number of repeating different structures, including phenolic units of 5-carbon building blocks acids, such benzoic and hydroxycinnamic (isoprene units), such as monoterpenes acids, flavonoids such as flavonols and with 10 carbons, sesquiterpenes with flavones, stilbenes and lignans [6]. In 15carbons, and triterpenes derived froma Cannabis, about 20 flavonoids have been 30-carbon skeleton. Terpene yield and identified, mainly belonging to the distribution in the plant vary according flavones and flavonol sub classes [17]. to numerous parameters, such as These include the O-glycoside versions of processes for obtaining essential oil, the aglycones apigenin, luteolin, environmental conditions, or maturity of kaempferol and quercetin, as well as the plant [24] [25]. Mono-and cannflavin A and cannflavin B, which are sesquiterpenes have been detected in methylated isoprenoid flavones that are flowers, roots, and leaves of Cannabis, unique to Cannabis [20]. with the secretory glandular hairs as main Phenolic amides and ligninamides have production site. Monoterpenes dominate also been described in Cannabis fruits generally the volatile terpene profile and and roots [8]; [9]. The lignanamides include mainly D-limonene, β-myrcene, α- belong to the lignan class of compounds

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www.idosr.org Moore and include cannabisin-like compounds induced in Cannabis leaves by UV (of the types A-,B-,C-,D-,E-,F-,and G) and radiations [20]. grossamide [23]. Similar compounds such Noncannabinoid as cannabisin D, have been described in Noncannabinoid, the geranylated flavone Cannabis leaves, where it was strongly cannflavin A (Figure 4), is 30 times more induced upon the UV-C treatment [21]. potent than aspirin as an inhibitor of Interesting amounts of lignans were [27] [28]. Six new non- recently found in the hydrophilic extract cannabinoid constituents were isolated of hempseeds. The hempseed lignin from a high potency Cannabis sativa L. profile was shown to be dominated by variety, namely 5-acetoxy-6- geranyl-3-n- syringaresinol and medioresinol, followed pentyl-1,4-benzoquinone, 4,5-dihydroxy- by secoisolariciresinol, lariciresinol, and 2,3,6- trimethoxy-9,10- pinoresinol [25]. Hempseeds contain, dihydrophenanthrene, 4,7-dimethoxy- however, about 20-times less total lignans 1,2,5-trihydroxyphenanthrene, cannflavin than flax seeds, a well-known source of C and b-sitosteryl-3-O-b-D- lignans. glucopyranoside-20- O-palmitate, 4- Interestingly, the lignin content of hulled hydroxy-2,3,6,7- tetramethoxy-9,10- hemp seeds represents only 1% of the dihydrophenanthrene. In addition, five content in whole seed [3]. Nineteen known compounds, a-cannabispiranol, stilbenes have been isolated in Cannabis , 6- prenylapigenin, cannflavin with characteristic structural back bones A and b-acetyl cannabispiranol were such as spirans, phenanthrenes and identified. Non-cannabinoid constituents bibenzyls [17]. They include molecules isolated from cannabis include such as cannabistilbene I, IIa and IIb, as flavonoids, spiroindans, dihydrostilbenes, well as dihydroresveratrol. Interestingly, dihydrophenanthrenes, sterols and bibenzyl stilbenes, including the putative alkaloids, among others [8] [9]. 3-O methylbatatasin, were strongly CONCLUSION Cannabis sativa is a unique versatile chemotherapy-derived nausea and plant, which can provide high biomass anorexia, and symptomatic mitigation of quantities in a short time. To date, more multiple sclerosis. Cannabis medicinal than 540 phytochemicals have been use and much research still need to be described in Cannabis and their undertaken to provide patients with a pharmacological properties appear to go medicine that is safe, efficacious and of much beyond psychotic effects, with the the appropriate quality. capacity to address needs like the relief of REFERENCES 1. Andre, C. M., Schafleitner, R.., 3. Cannabis. 1st ed. Oxford: Oxford Legay, S., Lefèvre, I., Aliaga, C. A. University Press; 2014. 3 - 22. and Nomberto, G. (2009).Gene 4. Chandra, S., Lata, H., Khan, I. A. expression changes related to the and ElSohly, M. A. (2013). The role production of phenolic compounds of biotechnology in Cannabis in potato tubers grown under sativa propagation for the drought stress. Phytochemistry 70: production of phytocannabinoids. 1107-1116. In: Chandra S, Lata H, Varma A, 2. Brenneisen, R. (2007). Chemistry editors. Biotechnology for and analysis of phytocannabinoids Medicinal Plant. Berlin Heidelberg: and other cannabis constituents,” Springer Verlag; 123-148. in Marijuana and the Cannabinoids 5. Docimo, T., Consonni, R., Forensic Science and Medicine, ed. Coraggio, I. and Mattana, M. M. ElSohly (2013). Early phenyl propanoid (NewYork,NY:HumanaPress), 17 – biosynthetic stepsin Cannabis 49. sativa, Int. J. Mol. Sci., 14: 136 - 144.

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