Keywords

2.1 Introduction

Cannabis is an erect, annual, dioecious and economically important aromatic medicinal herb belonging to the cannabaceae family (Pellati et al. 2018). The origination of cannabis was believed to be from Central Asia about ~500 BC (Farag and Kayser 2017). Plants belongs to this genus are well grown in wet land sites and near water bodies, where the concentration of nitrogen are found high (Small 2015). Cannabis is highly used and described genus in Ayurveda to provide various pharmacological bioactive compounds and benefits. Now a days, people take interest in this multipurpose plant due to the presence of high content of various nutrients along with bioactive therapeutic compounds having analgesic, anti-spasmodic, anti-tumour, anti-inflammatory, anti-oxidant, antineoplastic, neuro-protective, immunosuppressive, anti-nociceptive, antiepileptic, and anti-depressant properties (Carchman et al. 1976; Ameri et al. 1999; Callaway 2004; Gomes et al. 2008; Appendino et al. 2011) Cannabinoids, the major fundamental phytoconstituent of this genus which are chemically a unique class of terpenophenolic compounds having pharmaceutical potential such as anti0inflammatory, anti-cancer, antimicrobial, anti-arthritic, neuro antioxidative, etc. (De Petrocellis et al., 2011). Apart from this, hemp is also used by the mankind as natural fibres in the textile industry and as seed oil in the cosmetic production (Gautam et al. 2013; Clarke and Merlin 2013; Russo et al. 2008; Farag and Kayser 2017). Hemp use as a suitable eco-friendly option for phyto-remediation and bio fuel production has also been reported (Kumar et al. 2017).

Hemp is a highly variable species in plant system and it has been a matter of debate that whether the genus Cannabis having one species or more than one species (Chandra et al. 2017). According to Hazekamp and Fischedick (2012), Cannabis is a monotypic genus and consists a single species namely Cannabis sativa (described by Leonard Fuchs in the sixteenth century). Approximately 700 different varieties/cultivars of Cannabis have been identified and distinguished by the plant breeders and recreational users due to the results of centuries of breeding and selection. However, it is unclear whether or not these cultivars reflect any relevant differences in chemical composition.

2.2 Varieties of Hemp

With the course of time, different varieties of hemp have been evolved as the result of plant breeding and selection programme. Till so far, no in-dept study on the monospecific or/and polyspecific character of genus Cannabis has been made. According to the (United Nations Office on Drugs and Crime (UNODC) hemp is divided into three different categories like (a) fiber hemp (b) oil seed hemp and (c) drug hemp (Farag and Kayser 2017). Similarly, Schultes et al. (1974) also differentiated this genus into three species such as C. sativa L., C. indica L., and C. ruderalis. However, many reports are available on Cannabis is monotypic genus that consist only a single species C. sativa (Beutler and Dermarderosian 1978; Hoffmann 1961). Small and Cronquist (1976) divided the monotypic species C. sativa into the subspecies ‘sativa’ and ‘indica’ each with two different variants i.e., domesticated (C. sativa subsp. sativa var. sativa and C. sativa subsp. indica var. indica) and wild varieties (C. sativa subsp. sativa var. spontama and C. sativa subsp. indica var. kafiristanica). In last two decades, various new hybrid varieties have been also developed like ‘Super-sativa’, ‘Bedrocan’, ‘Bedrobinol’, and ‘Bediol’ etc. (Clarke and Watson 2002; de Meijer 2004; Flemming et al. 2007). Many Cannabis hybrid varieties and some pure strains have been now commercialized by many private farms and ~20 strains are well defined for the cultivation of Hemp. A large number of plant breeders cultivate fiber hemp variety with the target to reduce THC concentration (de Meijer 1995). During the origination process of plant, particularly Hemp opened the path to hybridization and leads the development of thousands of cultivars. Small (2015) stated that there is a serious taxonomic issue to classify the different strains of Cannabis and divide the C. sativa L. species into 3 subspecies or variants such as ‘sativa’ (industrial cannabis/hemp having a limited amount of tetrahydrocannabinol or THC), ‘indica’ (medicinal cannabis/marijuana producing principally THC), and ‘ruderalis’ (known for wild hemp strains). Clarke and Merlin (2016) referred C. ruderalis as ancestor of two modern Cannabis sp. (C. sativa and C. indica), originated from central Asia. The recent taxonomy of Cannabis was given by Clarke and Merlin (2016) as presented in Fig. 2.1.

Fig. 2.1
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Modern Cannabis taxonomy given by Clarke and Merlin (2016). Abbreviation: NLH = narrow leaflet hemp; BLH = broad leaflet hemp; NLD = narrow leaflet drug; BLD = broad leaflet drug; CBD = cannabidiol, and THC = delta-9-tetrahydrocannabinol

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2.3 Geographical Distribution

Cannabis has usually a wide range of geographical and ecological distribution. It is grown worldwide except Antarctica, in a broad range of environment from sub-arctic to temperate and tropical from sea level to over 3000 m elevation (Clarke and Merlin 2013; Glanzman 2015). This genus is believed to have originated in the Northwest Himalayas and widely distributed in the range of Africa. Small and Cronquist (1976) reported that genus Cannabis, geographically distributed towards latitude 30°N (North) and 60°N (South) (Hillig 2005).

Clarke and Merlin (2013), reported that Cannabis is distributed worldwide by humans for multiple purposes. According to the authors, the putative ancestor of Cannabis is originated in Central Asia. It is hypothesized that Cannabis distributed into new geographical areas and evolved into 4 taxonomic groups along with gene pools as Cannabis sativa narrow leaflet hemp (NLH), C. indica broad leaflet hemp (BLH), C. indica narrow leaflet drug (NLD), Cannabis indica spp. afghanica broad leaflet drug (BLD). Based on the broad taxonomic groups the worldwide distribution of Cannabis is given in Fig. 2.2.

Fig. 2.2
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Graphical distribution of Cannabis subspecies (Clarke and Merlin 2016)

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2.4 Genetic Diversity

Identification of functional gene variation and trait mapping is important step for understanding toward the evolutionary and functional aspects of Cannabis. Hemp possesses diploid genome (2n = 20) with difference in sizes as 818 Mb for female and 843 Mb for males (Sakamoto et al. 1998). Inspite of being restricted due to legalization stautus various authors attempted to study the hemp genetic for various traits like fiber quality, sex determination, sex expression, assessment of population diversity, and genetic relatedness between strains using various genetic tools etc. The genomic markers used for various trait mapping in hemp species are described in Table 2.1.

Table 2.1 Genetic markers/tools used for the study genetic diversity studies in Cannabis sativa (Hamp)
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Various issues regarding naming, breeding and quality control arises in hemp varieties cultivation. According to Lynch et al. (2016) and Schwabe et al. (2019) traditional classification did not determine the genetic relationship in drug-type and fibre-type Cannabis species i.e., ‘indica’ and ‘sativa’. Both drug-type and fiber-type C. sativa plants are genetically different and have been used for breeding practices for various purposes (van Bakel et al. 2011; Sawler et al. 2015; Lynch et al. 2016; Vergara et al. 2021). Previous studies usually focused on Cannabis species having high CBD/low THC but sometime these are closely related to marijuana species (Grassa et al. 2021). However, both types have been practicing to bred for specific compound production like cannabinoids and terpenoids. Cannabis genetics evolving with focus on C. sativa marijuana-type as compared to CBD-type hemp (Lynch et al. 2016; Vergara et al. 2021, Johnson and Wallace 2021).

2.5 Chemical Diversity in Cannabis Sativa

Apart from being controversial crop for various issues related to taxonomic status, origin, morphological and ecological diversity, Cannabis exhibited extensive phytochemical diversity in particular reference to cannabinoid and terpenoid (Hillig and Mahlberg 2004). Phytocannabinoids are the dominant chemical class of genus Cannabis. Cannabinoids are terpenophenolic compounds which are chemically associated terpenes with its ring structure derived from C10 monoterpene subunit i.e., geranyl pyrophosphate. Geranyl pyrophosphate are the biogenetic origin of cannabinoids (Hanus et al. 2016). Two independent pathways namely cytosolic mevalonate and plastidial methylerythritol phosphate (MEP) are responsible for phytoterpene biosynthesis. MEP pathway is reported for the biosynthesis of the cannabinoid terpenoid moiety biosynthesis (Sirikantaramas et al. 2007; ElSohly et al. 2017). The cannabinoids accumulated in cannabis plant as cannabinoid acids and non-enzymatically decarboxylated into their neutral forms during storage (Small 2015). Radwan et al. (2021) reviewed the phytochemistry, isolation, identification and structural elucidation of more than 500 constituents including cannabinoids and non-cannabinoids class of C. sativa. To date different secondary metabolites class of C. sativa were presented in Table 2.2. The chemical structures of cannabinoids and terpenoids compounds are presented in Figs. 2.3 and 2.4.

Table 2.2 Chemical diversity of Cannabis sativa (Radwan et al. 2021)
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Fig. 2.3
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Cannabinoids compounds in hemp

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Fig. 2.4
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Terpenoids compounds of hemp

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2.6 Chemotaxonomic Classification of Hemp

Chemotaxonomy/chemosystematics is used to classify according to confirmable differences and similarities in their biochemical compositions. According to Small (1979a) amount of THC in Cannabis is essential for taxonomic characterization. Gas chromatography-flame ionization detection (GC-FID) is commonly used techniques to differentiate indica strains from sativa strains on the basis of THC content (Small and Beckstead 1973a, Small et al. 1975; Small and Cronquist 1976). Numerous phytochemical markers used for chemotaxonomic classification of Cannabis species/varieties are presented in Table 2.3. Based on the quantitative difference in the cannabinoids ratio of tetrahydrocannabinol acid (THC), cannabinol (CBN) and cannabidiol (CBD), in the ratio of (THC) + (CBD)/(CBN) C. sativa classified in three different chemical phenotypes. If THC/CBD > 1 phenotype I (drug- type), THC/CBD = 1 phenotype II (intermediate type) THC/CBD < 1 phenotype III (fibre- type or hemp) (de Meijer et al. 2003; De Backer et al. 2009; Galal et al. 2009).

Table 2.3 Analytical methods used for chemotaxonomic classification and phytochemical quantification of Cannabis sp.
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Health benefits associated to cannabinoids and non-cannabinoids have been presented in Table 2.4. The biological properties related to cannabinoids mainly associated with human endocannabinoid system. The system consists of two G-protein coupled receptors i.e., CB1 and CB2 along with two ligands. The system mainly thought to regulatory role in various physiological processes including pain-sensation, mood, apatite, memory, inflammation and metabolic pathways. CB1 receptors also present on cells of gastrointestinal, adrenal, lung, heart and immune systems however, CB2 receptors exerted immunomodulary effect (Andre et al. 2016). Similarly, terpenes and phenolic compounds linked to Cannabis sp. possesses various biological activities (Table 2.4).

Table 2.4 Pharmaceutical potential of cannabinoids and non-cannabinoids compounds of Cannabis sativa
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2.7 Conclusion and Future Prospects

Despite of being controversial status of genus Cannabis, it is cultivated worldwide for its high pharmaceutical and industrial potential. Although, chemotaxonomy plays an important role to differentiate various varieties of hemp, but, the origination history and genetic diversity of Cannabis species still remain largely unexplored. As identification of elite chemotype is essential for production of cannabinoid for industrial use, it is paramount to first study genetic and chemical diversity of the plant in details. Considering high medicinal value of Indian varieties, it is essential for the scientific community to start working on this important medicinal agriculture crop. This will not only facilitate in drug discovery programme but can be proved as a boon for the marginal communities of the Himalayan region where this plant is growing as a weed.