Cultivating Research Grade Cannabis for the Development of Phytopharmaceuticals

  • Hemant Lata
  • Suman Chandra
  • Esther E. Uchendu
  • Ikhlas A. Khan
  • Mahmoud A. ElSohlyEmail author


Cannabis has been used as medicine since ancient times in different forms. With over 500 known constituents, of which cannabinoids are the most important class (120 known). Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD) are the two major natural cannabinoids having very different pharmacological profiles with tremendous therapeutic potential. After the discovery of Δ9-THC, the main psychoactive compound in cannabis, research had been revolving around Δ9-THC and its derivatives. Cannabidiol, a non-psychoactive compound which was discovered before Δ9-THC did not receive much attention for a long time. However, in last few years, research has intensified on CBD or CBD rich cannabis varieties due to its therapeutic potential in the treatment of a variety of ailments including childhood epilepsy (Dravet syndrome) and other disorders. In this chapter, we address cannabis botany, chemistry, its indoor and outdoor cultivation, harvesting, processing and its current status as a botanical drug.


Cannabis THC CBD Botanical drug Epilepsy 



This work was supported in part by the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Department of Health and Human Services, USA, under the contract no. N01DA-15-7793.


  1. Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC, Petersen KL (2007) Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurologija 68:515–521CrossRefGoogle Scholar
  2. Adams R, Baker BR, Wearn RB (1940a) Structure of cannabinol. III. Synthesis of cannabinol, 1-hydroxy-3-amyl-6,6,9-trimethyl-6-dibenzopyran. J Am Chem Soc 62:2204–2207CrossRefGoogle Scholar
  3. Adams R, Hunt M, Clark JH (1940b) Structure of cannabidiol, a product isolated from the marihuana extract of Minnesota wild hemp Int. J Am Chem Soc 62:196–200CrossRefGoogle Scholar
  4. Cahn RS (1932) Cannabis indica resin. III. Constitution of cannabinol. J Chem Soc 3:1342–1353CrossRefGoogle Scholar
  5. Cascio MG, Pertwee RG, Marini P (2017) The pharmacology and therapeutic potential of plant cannabinoids. In: Chandra S, Lata H, ElSohly MA (eds) Cannabis Sativa L.: botany and biotechnology. Springer, Basel, pp 207–226CrossRefGoogle Scholar
  6. Chandra S, Lata H, Khan IA, ElSohly MA (2008) Photosynthetic response of Cannabis sativa L. to variations in photosynthetic photon flux densities, temperature and CO2 conditions. Physiol Mol Biol Plants 14:299–306PubMedCrossRefGoogle Scholar
  7. Chandra S, Lata H, Khan IA, ElSohly MA (2009) Variations in temperature response of photosynthesis in drug and fiber type varieties of Cannabis sativa L. 8th annual Oxford international conference on the science of botanicals abstracts. Planta Med 75:415Google Scholar
  8. Chandra S, Lata H, Khan IA, Mehmedic Z, ElSohly MA (2010) Assessment of cannabinoids content in micropropagated plants of Cannabis sativa L. and their comparison with conventionally propagated plants and mother plant during developmental stages of growth. Planta Med 76:743–750PubMedCrossRefGoogle Scholar
  9. Chandra S, Lata H, Khan IA, ElSohly MA (2011a) Temperature response of photosynthesis in different drug and fiber varieties of Cannabis sativa L. Physiol Mol Biol Plants 17(3):297–303PubMedPubMedCentralCrossRefGoogle Scholar
  10. Chandra S, Lata H, Khan IA, ElSohly MA (2011b) Photosynthetic response of Cannabis sativa L., an important medicinal plant, to elevated levels of CO2. Physiol Mol Biol Plants 17(3):291–295PubMedPubMedCentralCrossRefGoogle Scholar
  11. Chandra S, Lata H, Khan IA, Mehmedic Z, ElSohly MA (2015) Light dependence of photosynthesis and water vapour exchange characteristics in different high Δ9-THC yielding varieties of Cannabis sativa L. J Appl Res Med Aromat Plants 2(2):39–47Google Scholar
  12. Chandra S, Lata H, ElSohly MA, Walker LA, Potter D (2017) Cannabis cultivation: methodological issues for obtaining medical-grade product. Epilepsy Behav 70:302–312PubMedCrossRefGoogle Scholar
  13. Cunha JM, Carlini EA, Pereira AE, Ramos OL, Pimentel C, Gagliardi R, Sanvito WL, Lander N, Mechoulam R (1980) Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 21:175–185PubMedCrossRefGoogle Scholar
  14. Doyle E, Spence AA (1995) Cannabis as a medicine? Br J Anesth 74:359–361CrossRefGoogle Scholar
  15. ElSohly MA, Gul W (2014) Constituents of Cannabis sativa. In: Pertwee RG (ed) Handbook of Cannabis. Oxford University Press, Oxford, pp 3–22CrossRefGoogle Scholar
  16. ElSohly MA, Slade D (2005) Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 78:539–548PubMedCrossRefGoogle Scholar
  17. Emboden WA (1974) Cannabis, a polytypic genus. Econ Bot 28:304–310CrossRefGoogle Scholar
  18. FDA (2006) Botanical Drug Development Guidance for Industry. Accessed 03 Sep 2018
  19. Fellermeier M, Zenk MH (1998) Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEBS Lett 427:283–285PubMedCrossRefGoogle Scholar
  20. Flores-Sanchez IJ, Verpoorte R (2008a) Secondary metabolism in cannabis. Phytochem Rev 7:615–639CrossRefGoogle Scholar
  21. Flores-Sanchez IJ, Verpoorte R (2008b) PKS activities and biosynthesis of cannabinoids and flavonoids in C. sativa L. plants. Plant Cell Physiol 49:1767–1782PubMedCrossRefGoogle Scholar
  22. Gaoni Y, Mechoulam R (1964) Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 86:1646CrossRefGoogle Scholar
  23. Ghosh R, Todd AR, Wilkinson S (1940) Cannabis indica. Part IV. The synthesis of some tetrahydrodibenzopyran derivatives. J Am Chem Soc:1121–1125Google Scholar
  24. Gilmore S, Peakall R, Robertson J (2003) Short tandem repeat (STR) DNA markers are hypervariable and informative in Cannabis sativa: implications for forensic investigations. Forensic Sci Int 131:65–74PubMedCrossRefGoogle Scholar
  25. Hillig KW (2004) A chemotaxonomic analysis of terpenoid variation in Cannabis. Biochem Syst Ecol 32:875–891CrossRefGoogle Scholar
  26. Hillig KW (2005) Genetic evidence for speciation in Cannabis (Cannabaceae). Genet Resour Crop Evol 52:161–180CrossRefGoogle Scholar
  27. Hillig KW, Mahlberg PG (2004) A chemotaxonomic analysis of cannabinoids variation in Cannabis (Cannabaceae). Am J Bot 91:966–975PubMedCrossRefGoogle Scholar
  28. Kajima M, Piraux M (1982) The biogenesis of cannabinoids in Cannabis sativa. Phytochemistry 21:67–69CrossRefGoogle Scholar
  29. Kriese U, Schumann E, Weber WE, Beyer M, Brhl L, Matthus B (2004) Oil content, tocopherol composition and fatty acid patterns of the seeds of 51 Cannabis sativa L. genotypes. Euphytica 137:339–351CrossRefGoogle Scholar
  30. Lamark JB (1785) Encyclope’die me’todique. Botanique, Paris-Liege, pp 1783–1803Google Scholar
  31. Lata H, Chandra S, Khan IA, ElSohly MA (2009a) Thidiazuron induced high frequency direct shoot organogenesis of Cannabis sativa L. In vitro cellular and developmental biology. Planta 45:12–19Google Scholar
  32. Lata H, Chandra S, Khan I, ElSohly MA, ElSohly MA (2009b) Propagation through alginate encapsulation of axillary buds of Cannabis sativa L.—an important medicinal plant. Physiol Mol Biol Plants 15(1):79–86PubMedPubMedCentralCrossRefGoogle Scholar
  33. Lata H, Chandra S, Khan IA, ElSohly MA (2010a) High frequency plant regeneration from leaf derived callus of high Δ9-tetrahydrocannabinol yielding Cannabis sativa L. Planta Med 76:1629–1633PubMedCrossRefGoogle Scholar
  34. Lata H, Chandra S, Techen N, Khan IA, ElSohly MA (2010b) Assessment of genetic stability of micropropagated plants of Cannabis sativa L. by ISSR markers. Planta Med 76:97–100PubMedCrossRefGoogle Scholar
  35. Lata H, Chandra S, Techen N, Khan IA, ElSohly MA (2012) In vitro germplasm conservation of high Δ9-tetrahydrocannabinol yielding elite clones of Cannabis sativa L. under slow growth conditions. Acta Physiol Plant 34(2):743–750CrossRefGoogle Scholar
  36. Lata H, Chandra S, Techen N, Wang YH, Khan IA (2013) Molecular analysis of genetic fidelity in micropropagated plants of Stevia rebaudiana Bert. using ISSR markers. Am J Plant Sci 4:964–971CrossRefGoogle Scholar
  37. Lata H, Chandra S, Techen N, Khan IA, ElSohly MA (2016) In vitro mass propagation of Cannabis sativa L.: a protocol refinement using a novel aromatic cytokinin meta-topolin and assessment of eco-physiological, biochemical and genetic fidelity of micropropagated plants. J Appl Res Med Aromat Plants 3(1):18–26Google Scholar
  38. Linnaeus C (1737) Species plantarum. Laurentius Salvius, Stockholm, p 1753Google Scholar
  39. Mechoulam R, Carlini E (1978) Toward drugs derived from Cannabis. Naturwissenschaften 65:174–179PubMedCrossRefGoogle Scholar
  40. Mechoulam R, Shvo Y (1963) The structure of cannabidiol. Tetrahedron 19:2073–2078PubMedCrossRefGoogle Scholar
  41. Pertwee RG (2006) Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 147:S163–S171PubMedPubMedCentralCrossRefGoogle Scholar
  42. Potter D (2015) Cannabis horticulture. In: Pertwee RG (ed) Handbook of Cannabis. Oxford University Press, Oxford, pp 64–88Google Scholar
  43. Pryce G, Baker D (2005) Emerging properties of cannabinoid medicines in management of multiple sclerosis. Trends Neurosci 28:272–276PubMedCrossRefGoogle Scholar
  44. Radwan MM, Wanas AS, Chandra S, ElSohly MA (2017) Natural cannabinoids of Cannabis and methods of analysis. In: Chandra S, Lata H, ElSohly MA (eds) Cannabis Sativa L.: Botany and Biotechnology. Springer, Basel, pp 161–182CrossRefGoogle Scholar
  45. Ranalli P, Candilo MD, Mandolino G, Grassi G, Carboni A (1999) Hemp for sustainable agricultural systems. Agro Industry 10:33–38Google Scholar
  46. Shoyama Y, Hirano H, Oda M, Somehara T, Nishioka I (1975) Cannabis. IX. Cannabichromevarin and cannabigerovarin, two new propyl homologs of cannabichromene and cannabigerol. Chem Pharm Bull 23:1894–1895CrossRefGoogle Scholar
  47. Sirikantaramas S, Taura F, Morimoto S, Shoyama Y (2007) Recent advances in Cannabis sativa research: biosynthetic studies and its potential in biotechnology. Curr Pharm Biotechnol 8(4):237–243PubMedCrossRefGoogle Scholar
  48. Small E (1975a) Morphological variation of Cannabis. Can J Bot 53(10):978–987CrossRefGoogle Scholar
  49. Small E (1975b) American law and the species problem in Cannabis. Sci Semant Bull Narcotics 27:1–20Google Scholar
  50. Small E (2017) Classification of Cannabis sativa L. in relation to agricultural, biotechnological, medical and recreational utilization. In: Chandra S, Lata H, ElSohly MA (eds) Cannabis Sativa L.: Botany and Biotechnology. Springer, Basel, pp 1–62Google Scholar
  51. Small E, Beckstead HD (1973a) Cannabinoid phenotypes in Cannabis sativa. Nature 245:147–148PubMedCrossRefGoogle Scholar
  52. Small E, Beckstead HD (1973b) Common cannabinoid phenotypes in 350 stocks of Cannabis. Lloydia 36:144–165PubMedGoogle Scholar
  53. Small E, Cronquist A (1976) A practical and natural taxonomy for Cannabis. Taxon 25:405–435CrossRefGoogle Scholar
  54. Turner CE, ElSohly MA, Boeren EG (1980) Constituents of C. sativa L. XVII. A review of the natural constituents. J Nat Prod 43:169–234PubMedCrossRefGoogle Scholar
  55. Wood TB, Spivey WTN, Easterfield TH (1899) III-Cannabinol. Part I. J Chem Soc Trans 75:20–36CrossRefGoogle Scholar
  56. Zuardi AW (2006) History of Cannabis as a medicine: a review. Braz J Psychiatry 28:153–157PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Hemant Lata
    • 1
  • Suman Chandra
    • 1
  • Esther E. Uchendu
    • 1
    • 2
  • Ikhlas A. Khan
    • 1
    • 3
  • Mahmoud A. ElSohly
    • 1
    • 4
    Email author
  1. 1.National Center for Natural Products Research, School of PharmacyUniversity of MississippiUniversityUSA
  2. 2.Faculty of Agriculture, Department of AgronomyUniversity of IbadanIbadanNigeria
  3. 3.Department of Biomolecular Sciences, School of PharmacyUniversity of MississippiUniversityUSA
  4. 4.Department of Pharmaceutics and Drug Delivery, School of PharmacyUniversity of MississippiUniversityUSA

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