1371Accesses
25Citations
9Altmetric
Abstract
In order to complete a genetic model for the inheritance of chemotype inCannabis, this paper explores the regulation of the propyl-/pentyl cannabinoid ratio. Plants almost pure in compounds with a C5 side chain are by far the most common, and such a chemotype can be considered a wild-type condition. Mutant progenitors with higher levels of the rarer cannabinoid THC-C3 (tetrahydrocannabivarin) were identified. Their propyl cannabinoid proportion in the total cannabinoid fraction (PC3) ranged from 14 to 69 %, which, through selective inbreeding, could be increased to highly specific lineage maxima. Inbred plants with maximised PC3 derived from the different progenitors, were then crossed with a pure C5 wild type and the PC3 distribution patterns of the F2s examined. Distinct patterns, compatible with oligogenic and polygenic segregation appeared. It was hypothesised that the PC3 regulating loci of the six source progenitors would be at least partially different, complementary, and additive in their phenotypical effect. So, high PC3 offspring from the different lineages were mutually crossed. Inbred lines derived from multi-cross hybrid combinations reached unprecedented PC3 levels of up to 96 % which supports the hypothesis. For the regulation of C3/C5 ratios, a model of a multiple locusA1–A2–…An is proposed, with the pentyl- and propyl cannabinoid pathway being enhanced by allelesA1−npe andA1−npr, respectively.
This is a preview of subscription content,log in via an institution to check access.
Access this article
Subscribe and save
- Get 10 units per month
- Download Article/Chapter or eBook
- 1 Unit = 1 Article or 1 Chapter
- Cancel anytime
Buy Now
Price includes VAT (Japan)
Instant access to the full article PDF.






Similar content being viewed by others
References
Adams R, Hunt M, Clark JH (1940) Structure of cannabidiol, a product isolated from the marihuana extract of Minnesota wild hemp. J Am Chem Soc 62:196–200
Baker PB, Gough TA, Taylor BJ (1980) Illicitly importedCannabis products: some physical and chemical features indicative of their origin. Bull Narc 32:31–41
Baker PB, Gough TA, Taylor BJ (1983) The physical and chemical features ofCannabis plants grown in the United Kingdom of Great Britain and Northern Ireland from seeds of known origin-Part II: second generation studies. Bull Narc 35:51–62
Basile A (2014) Understanding the regulating mechanisms behind cannabinoid synthesis. Dissertation, Scuola Superiore Sant’Anna, Pisa
Bohlmann F, Hoffmann E (1979) Cannabigerol-ähnliche verbindungen ausHelichrysum umbraculigerum. Phytochemistry 18:1371–1374
Boucher F, Paris M, Cosson L (1977) Mise en évidence de deux types chimiques chez leCannabis sativa originaire d’Afrique du Sud. Phytochemistry 16:1448–1450
De Meijer EPM, Hammond KM (2005) The inheritance of chemical phenotype inCannabis sativa L. (II): cannabigerol predominant plants. Euphytica 145:189–198
De Meijer EPM, Bagatta M, Carboni A, Crucitti P, Moliterni VMC, Ranalli P, Mandolino G (2003) The inheritance of chemical phenotype inCannabis sativa L. Genetics 163:335–346
De Meijer EPM, Hammond KM, Micheler M (2009a) The inheritance of chemical phenotype inCannabis sativa L. (III): variation in cannabichromene proportion. Euphytica 165:293–311
De Meijer EPM, Hammond KM, Sutton A (2009b) The inheritance of chemical phenotype inCannabis sativa L. (IV): cannabinoid-free plants. Euphytica 168:95–112
De Petrocellis L, Ligresti A, Schiano Moriello A, Allarà M, Bisogno T, Petrosino S, Stott CG, di Marzo V (2011) Effects of cannabinoids and cannabinoid-enrichedCannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol 163:1479–1494
Den Nijs APM, Visser DL (1980) Induction of male flowering in gynoecious cucumbers (Cucumis sativus L.) by silver ions. Euphytica 29:273–280
Fellermeier M, Zenk MH (1998) Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEBS Lett 427:283–285
Fellermeier M, Eisenreich W, Bacher A, Zenk MH (2001) Biosynthesis of cannabinoids. Incorporation experiments with13C-labeled glucoses. Eur J Biochem 268:1596–1604
Flores-Sanchez IJ, Verpoorte R (2008) Secondary metabolism inCannabis. Phytochem Rev 7:615–639
Flores-Sanchez IJ, Linthorst HJM, Verpoorte R (2010)In silico expression analysis of PKS genes isolated fromCannabis sativa L. Genet Mol Biol 33:703–713
Gagne SJ, Stout JM, Liu E, Boubakir Z, Clark SM, Page JE (2012) Identification of olivetolic acid cyclase fromCannabis sativa reveals a unique catalytic route to plant polyketides. Proc Natl Acad Sci 109:12811–12816. doi:10.1073/pnas.1200330109
Gaoni Y, Mechoulam R (1964a) Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 86:1646–1647
Gaoni Y, Mechoulam R (1964b) The structure and synthesis of cannabigerol a new hashish constituent. Proc Chem Soc London, March 1964:82
Gaoni Y, Mechoulam R (1966) Cannabichromene, a new active principle in hashish. Chem Commun 1:20–21
Harvey DJ (1976) Characterization of the butyl homologues of Δ1-tetrahydrocannabinol, cannabinol and cannabidiol in samples of cannabis by combined gas chromatography and mass spectrometry. J Pharm Pharmacol 28:280–285
Isbell H (1973) Research on Cannabis (marihuana). Bull Narc 25:37–48
Marks MD, Tian L, Wenger JP, Omburo SN, Soto-Fuentes W, He J, Gang DR, Weiblen GD, Dixon RA (2009) Identification of candidate genes affecting 9-tetrahydrocannabinol biosynthesis inCannabis sativa. J Exp Bot 60:3715–3726
Mechoulam R, Shvo Y (1963) Hashish-I, the structure of cannabidiol. Tetrahedron 19:2073–2078
Morimoto S, Komatsu K, Taura F, Shoyama Y (1997) Enzymological evidence for cannabichromenic acid biosynthesis. J Nat Prod 60:854–857
Morimoto S, Komatsu K, Taura F, Shoyama Y (1998) Purification and characterization of cannabichromenic acid synthase fromCannabis sativa. Phytochemistry 49:1525–1529
Onofri C, De Meijer EPM, Mandolino G (2015) Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid synthase inCannabis sativa L. and its relationship with chemical phenotype. Phytochemistry 116:57–68. doi:10.1016/j.phytochem.2015.03.006
Page J, Boubakir Z (2011) Aromatic prenyltransferase from Cannabis. World Intellectual Property Organisation, International Publication Number WO 2011/017798 A1
Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215
Rowan MG, Fairbairn JW (1977) Cannabinoid patterns in seedlings ofCannabis sativa L. and their use in the determination of chemical race. J Pharm Pharmacol 29:491–494
Shoyama Y, Yagi M, Nishioka I, Yamauchi T (1975) Biosynthesis of cannabinoid acids. Phytochemistry 14:2189–2192
Shoyama Y, Hirano H, Nishioka I (1984) Biosynthesis of propyl cannabinoid acid and its biosynthetic relationship with pentyl and methyl cannabinoid acids. Phytochemistry 23:1909–1912
Smith RM (1997) Identification of butyl cannabinoids in marijuana. J Forensic Sci 42:610–618
Stout JM, Boubakir Z, Ambrose SJ, Purves RW, Page JE (2012) The hexanoyl-CoA precursor for cannabinoid biosynthesis is formed by an acyl-activating enzyme inCannabis sativa trichomes. Plant J 71:353–365. doi:10.1111/j.1365-313X.2012.04949.x
Suzuki Y, Kurano M, Esumi Y, Yamaguchi I, Doi Y (2003) Biosynthesis of 5-alkylresorcinol in rice: incorporation of a putative fatty acid unit in the 5-alkylresorcinol carbon chain. Bioorg Chem 31:437–452
Taura F, Morimoto S, Shoyama Y, Mechoulam R (1995) First direct evidence for the mechanism of delta-1-tetrahydrocannabinolic acid biosynthesis. J Am Chem Soc 38:9766–9767
Taura F, Morimoto S, Shoyama Y (1996) Purification and characterization of cannabidiolic-acid synthase fromCannabis sativa L. J Biol Chem 271:17411–17416
Taura F, Tanaka S, Taguchi C, Fukamizu T, Tanaka H, Shoyama Y, Morimoto S (2009) Characterisation of olivetol synthase, a polyketide synthase putatively involved in cannabinoid biosynthetic pathway. FEBS Lett 583:2061–2066
Tubaro A, Giangaspero A, Sosa S, Negri R, Grassi G, Casano S, Della Loggia R, Appendino G (2010) Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins. Fitoterapia 81:816–819
Turner CE, Hadley K, Fetterman PS (1973) Constituents ofCannabis sativa L. VI: propyl homologs in samples of known geographical origin. J Pharm Sci 62:1739–1741
Vree TB, Breimer DD, van Ginneken CAM, van Rossum JM (1971) Identification of the methyl and propyl homologues of CBD, THC and CBN in hashish by a new method of combined gas chromatography-mass spectrometry. Acta Pharm Suec 8:683–684
Weiblen GD, Wenger JP, Craft KJ, ElSohly MA, Mehmedic Z, Treiber EL, Marks MD (2015) Gene duplication and divergence affecting drug content inCannabis sativa. New Phytol 208:1241–1250
Welling MT, Liu L, Shapter T, Raymond CA, King GJ (2016) Characterisation of cannabinoid composition in a diverseCannabis sativa L. germplasm collection. Euphytica 208:463–475. doi:10.1007/s10681-015-1585-y
Author information
Authors and Affiliations
GW Pharmaceuticals plc., Kingsgate House, Newbury Road, Andover, SP10 4DU, UK
E. P. M. de Meijer & K. M. Hammond
- E. P. M. de Meijer
You can also search for this author inPubMed Google Scholar
- K. M. Hammond
You can also search for this author inPubMed Google Scholar
Corresponding author
Correspondence toE. P. M. de Meijer.
Rights and permissions
About this article
Cite this article
de Meijer, E.P.M., Hammond, K.M. The inheritance of chemical phenotype inCannabis sativa L. (V): regulation of the propyl-/pentyl cannabinoid ratio, completion of a genetic model.Euphytica210, 291–307 (2016). https://doi.org/10.1007/s10681-016-1721-3
Received:
Accepted:
Published:
Issue Date:
Share this article
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative