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Secondary metabolism in cannabis

Abstract

Cannabis sativa L. is an annual dioecious plant from Central Asia. Cannabinoids, flavonoids, stilbenoids, terpenoids, alkaloids and lignans are some of the secondary metabolites present in C. sativa. Earlier reviews were focused on isolation and identification of more than 480 chemical compounds; this review deals with the biosynthesis of the secondary metabolites present in this plant. Cannabinoid biosynthesis and some closely related pathways that involve the same precursors are disscused.

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References

  • Adams M, Pacher T, Greger H, Bauer R (2005) Inhibition of leukotriene biosynthesis by stilbenoids from Stemona species. J Nat Prod 68:83–85

    PubMed  CAS  Google Scholar 

  • Ameri A (1999) The effects of cannabinoids on the brain. Prog Neurobiol 158:315–348

    Google Scholar 

  • André CL, Vercruysse A (1976) Histochemical study of the stalked glandular hairs of the female cannabis plants, using fast blue salt. Planta Med 29:361–366

    PubMed  Google Scholar 

  • Aronne LJ (2007) Rimonabant improves body weight and cardiometabolic risk factors in older adults. J Am Coll Cardiol 49-S1:325A

    Google Scholar 

  • Asakawa Y, Takikawa K, Toyota M, Takemoto T (1982) Novel bibenzyl derivatives and ent-cuparene-type sesquiterpenoids from Radula species. Phytochemistry 21:2481–2490

    CAS  Google Scholar 

  • Ayres DC, Loike JD (1990) Lignans: chemical, biological and clinical properties. In: Phillipson JD, Ayres DC, Baxter H (eds) Chemistry and Pharmacology of natural products. Cambridge University Press, UK

    Google Scholar 

  • Back K, Jang SM, Lee BC, Schmidt A, Strack D., Kim KM (2001) Cloning and characterization of a hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase induced in response to UV-C and wounding from Capsicum annuum. Plant Cell Physiol 42:475–481

    PubMed  CAS  Google Scholar 

  • Barrett ML, Scutt AM, Evans FJ (1986) Cannflavin A and B, prenylated flavones from Cannabis sativa L. Experientia 42:452–453

    PubMed  CAS  Google Scholar 

  • Barron D, Ibrahim RK (1996) Isoprenylated flavonoids-a survey. Phytochemistry 43:921–982

    CAS  Google Scholar 

  • Bercht CAL, Lousberg RJJC, Küppers FJEM, Salemink CA (1973) L-(+)-Isoleucine betaine in Cannabis seeds. Phytochemistry 12:2457–2459

    CAS  Google Scholar 

  • Bercht CAL, Samrah HM, Lousberg RJJC, Theuns H, Salemink CA (1976) Isolation of vomifoliol and dihydrovomifoliol from Cannabis. Phytochemistry 15:830–831

    CAS  Google Scholar 

  • Bernards MA (2002) Demystifying suberin. Can J Bot 80:227–240

    CAS  Google Scholar 

  • Bienz S, Detterbeck R, Ensch C, Guggisberg A, Häusermann U, Meisterhans C, Wendt B, Werner C, Hesse M (2002) Putrescine, spermidine, spermine and related polyamine alkaloids. In: Cordell GA (ed) The alkaloids, chemistry and pharmacology, vol 58. Academic Press, USA, pp 83–338

    Google Scholar 

  • Binder M, Popp A (1980) Microbial transformation of cannabinoids, part 3: major metabolites of (3R, 4R)-Δ1-Tetrahydrocannabinol. Helv Chim Acta 63:2515–2518

    CAS  Google Scholar 

  • Blokhina O, Virolainen E, Fagerstedt KV (2003) Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann Bot 91:179–194

    PubMed  CAS  Google Scholar 

  • Bohlmann F, Hoffmann E (1979) Cannabigerol-ähnliche verbindungen aus Helichrysum umbraculigerum. Phytochemistry 18:1371–1374

    CAS  Google Scholar 

  • Bosabalidis A, Gabrieli C, Niopas I (1998) Flavone aglycones in glandular hairs of Origanum x intercedens. Phytochemistry 49:1549–1553

    PubMed  CAS  Google Scholar 

  • Bouvier F, Rahier A, Camara B (2005) Biogenesis, molecular regulation and function of plant isoprenoids. Prog Lipid Res 44:357–429

    PubMed  CAS  Google Scholar 

  • Brady LR, Tyler VE (1958) Biosynthesis of hordenine in tissue homogenates of Panicum miliaceum L. Plant Physiol 33:334–338

    PubMed  CAS  Google Scholar 

  • Braemer R, Paris M (1987) Biotransformation of cannabinoids by cell suspension culture of Cannabis sativa L. Plant Cell Rep 6:150–152

    CAS  Google Scholar 

  • Braemer R, Braut-Boucher F, Cosson L, Paris M (1985) Exemple de variabilite induite par biotransformation du cannabidiol par des cals et des suspensions cellulaires de Cannabis sativa L. Bull Soc Bot Fr Actual Bot 132:148

    Google Scholar 

  • Braemer R, Tsoutsias Y, Hurabielle M, Paris M (1986) Biotransformations of quercetin and apigenin by a cell suspension culture of Cannabis sativa. Planta Med 53:225–226

    Google Scholar 

  • Bruneton J (1999) Lignans, neolignans and related compounds. In: Pharmacognosy, phytochemistry, medicinal plants, 2nd edn. Lavoisier Publishing Inc-Intercept Ltd., Paris, pp 279–293

  • Burstein S, Varanelli C, Slade LT (1975) Prostaglandins and cannabis-III: inhibition of biosynthesis by essential oil components of marihuana. Biochem Pharmacol 24:1053–1054

    PubMed  CAS  Google Scholar 

  • Carchman RA, Harris LS, Munson AE (1976) The inhibition of DNA synthesis by cannabinoids. Cancer Res 36:95–100

    PubMed  CAS  Google Scholar 

  • Chen JJ, Huang SY, Duh CY, Chen IS, Wang TC, Fang HY (2006) A new cytotoxic amide from the stem wood of Hibiscus tiliaceus. Planta Med 72:935–938

    PubMed  CAS  Google Scholar 

  • Chiron H, Drouet A, Lieutier F, Payer HD, Ernst D, Sanderman HJ (2000) Gene induction of stilbene biosynthesis in Scot pine in response to ozone treatment, wounding and fungal infection. Plant Physiol 124:865–872

    PubMed  CAS  Google Scholar 

  • Christensen AB, Gregersen PL, Schröder J, Collinge DB (1998) A chalcone synthase with an unusual substrate preference is expressed in barley leaves in response to UV light and pathogen attack. Plant Mol Biol 37:849–857

    PubMed  CAS  Google Scholar 

  • Clark MN, Bohm BA (1979) Flavonoid variation in Cannabis L. Bot J Linn Soc 79:249–257

    CAS  Google Scholar 

  • Clarke RC (1981) Marijuana botany: an advanced study, the propagation and breeding of distinctive Cannabis. Ronin Publishing, Oakland, CA

    Google Scholar 

  • Crombie L (1986) Natural products of Cannabis and Khat. Pure Appl Chem 58:693–700

    CAS  Google Scholar 

  • Crombie L, Crombie WML (1982) Natural products of Thailand high Δ1-THC-strain Cannabis: the bibenzyl-spiran-dihydrophenanthrene group, relations with cannabinoids and canniflavones. J Chem Soc Perkin Trans I:1455–1466

    Google Scholar 

  • Crombie L, Tuchinda P, Powell MJ (1982) Total synthesis of the spirans of Cannabis: cannabispiradienone, cannabispirenone-A and –B, cannabispirone, α- and β-cannabispiranols and the dihydrophenanthrene cannithrene-1. J Chem Soc Perkin Trans I:1477–1484

    Google Scholar 

  • Crombie L, Crombie WML, Firth DF (1988) Synthesis of bibenzyl cannabinoids, hybrids of two biogenetic series found in Cannabis sativa. J Chem Soc Perkin Trans I:1263–1270

    Google Scholar 

  • Davies KM, Schwinn KE (2003) Transcriptional regulation of secondary metabolism. Funct Plant Biol 30:913–925

    CAS  Google Scholar 

  • Davies KM, Schwinn KE (2006) Molecular biology and biotechnology of flavonoid biosynthesis. In: Andersen ØM, Markham KR (eds) Flavonoids: chemistry, biochemistry and applications. CRC Press-Taylor & Francis Group, Boca Raton, FL, pp 143–218

    Google Scholar 

  • Dewick PM (2002) Alkaloids. In: Medicinal natural products, a biosynthetic approach. 2nd edn. Wiley, England, pp 291–403

  • Di Marzo V, Bisogno T, De Petrocellis L (2007) Endocannabinoids and related compounds: walking back and forth between plant natural products and animal physiology. Chem Biol 14:741–756

    PubMed  CAS  Google Scholar 

  • Djoko B, Chiou RYY, Shee JJ, Liu YW (2007) Characterization of immunological activities of peanut stilbenoids, arachidin-1, piceatannol and resveratrol on lipopolysaccharide-induced inflammation of RAW 264.7 macrophages. J Agric Food Chem 55:2376–2383

    PubMed  CAS  Google Scholar 

  • Douglas CJ (1996) Phenylpropanoid metabolism and lignin biosynthesis: from weeds to trees. Trends Plant Sci 1:171–178

    Google Scholar 

  • El-Feraly FS, Turner CE (1975) Alkaloids of Cannabis sativa leaves. Phytochemistry 14:2304

    CAS  Google Scholar 

  • El-Feraly FS, El-Sherei MM, Al-Muhtadi FJ (1986) Spiro-indans from Cannabis sativa. Phytochemistry 25:1992–1994

    CAS  Google Scholar 

  • ElSohly MA (1985) Cannabis alkaloids. In: Pelletier SW (ed) Alkaloids, chemical and biological perspectives, vol 3. Wiley, NY, pp 169–184

    Google Scholar 

  • ElSohly MA, Slade D (2005) Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 78:539–548

    PubMed  CAS  Google Scholar 

  • ElSohly MA, Turner CE, Phoebe CH, Knapp JE, Schiff PL, Slatkin DJ (1978) Anhydrocannabisativine, a new alkaloid from Cannabis sativa. J Pharm Sci 67:124

    PubMed  CAS  Google Scholar 

  • ElSohly HN, Turner CE, Clark AM, ElSohly MA (1982) Synthesis and antimicrobial activities of certain cannabichromene and cannabigerol related compounds. J Pharm Sci 71:1319–1323

    Google Scholar 

  • Estrada-Soto S, Lopez-Guerrero JJ, Villalobos-Molina R, Mata R (2006) Endothelium-independent relaxation of aorta rings by two stilbenoids from the orchids Scaphyglottis livida. Fitoterapia 77:236–239

    PubMed  CAS  Google Scholar 

  • Fellermeier M, Zenk MH (1998) Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEBS Lett 427:283–285

    PubMed  CAS  Google Scholar 

  • Fellermeier M, Eisenreich W, Bacher A, Zenk MH (2001) Biosynthesis of cannabinoids: incorporation experiments with 13C-labeled glucoses. Eur J Biochem 268:1596–1604

    PubMed  CAS  Google Scholar 

  • Ferguson LR (2001) Role of plant polyphenols in genomic stability. Mutat Res 475:89–111

    PubMed  CAS  Google Scholar 

  • Fliegmann J, Schröder G, Schanz S, Britsch L, Schröder J (1992) Molecular analysis of chalcone and dihydropinosylvin synthase from Scots pine (Pinus sylvestris), and differential regulation of these and related enzyme activities in stressed plants. Plant Mol Biol 18:489–503

    PubMed  CAS  Google Scholar 

  • Formukong EA, Evans AT, Evans FJ (1988) Analgesic and antiinflammatory activity of constituents of Cannabis sativa L. Inflammation 12:361–371

    PubMed  CAS  Google Scholar 

  • Fritzemeier KH, Kindl H (1983) 9,10-dihydrophenanthrenes as phytoalexins of Orchidaceae: biosynthetic studies in vitro and in vivo proving the route from L-phenylalanine to dihydro-m-coumaric acid, dihydrostilbene and dihydrophenanthrenes. Eur J Biochem 133:545–550

    PubMed  CAS  Google Scholar 

  • Garcia ES, Azambuja P (2004) Lignoids in insects: chemical probes for the study of ecdysis, excretion and Trypanosoma cruzi-triatomine interactions. Toxicon 44:431–440

    PubMed  CAS  Google Scholar 

  • Gehlert R, Kindl H (1991) Induced formation of dihydrophenanthrenes and bibenzyl synthase upon destruction of orchid mycorrhiza. Phytochemistry 30:457–460

    CAS  Google Scholar 

  • Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M And Piomelli D (1999) Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 2:358–363

    PubMed  CAS  Google Scholar 

  • Goldstein JL, Brown MS (1990) Regulation of mevalonate pathway. Nature 434:425–430

    Google Scholar 

  • Gorham J (1980) The stilbenoids. In: Reinhold L, Harborne JB, Swain T (eds) Progress in Phytochemistry, vol. 6. Pergamon Press, Oxford, pp 203–252

    Google Scholar 

  • Gorham J, Tori M, Asakawa Y (1995) The biochemistry of stilbenoids. In: Harborne JB, Baxter H (eds) Biochemistry of natural products series, vol 1. Chapman & Hall, London

    Google Scholar 

  • Gould KS, Lister C (2006) Flavonoid functions in plants. In: Andersen ØM, Markham KR (eds) Flavonoids: chemistry, biochemistry and applications. CRC Press-Taylor & Francis Group, Boca Raton, FL, pp 397–441

    Google Scholar 

  • Grotenhermen F (2002) Review of therapeutic effects. In: Grothenhermen F, Russo E (eds) Cannabis and cannabinoids: pharmacology, toxicology and therapeutic potential. The Haworth Integrative Healing Press, New York, pp 123–142

    Google Scholar 

  • Hamada T (2005) New development of photo-induced electron transfer reaction and total synthesis of natural product. Yakagaku Zasshi 125:1–16

    CAS  Google Scholar 

  • Hammond CT, Mahlberg PG (1994) Phloroglucinol glucoside as a natural constituent of Cannabis sativa. Phytochemistry 37:755–756

    CAS  Google Scholar 

  • Hampson AJ, Grimaldi M, Axelrod J, Wink D (1998) Cannabidiol and (-) Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA 95:8268–8273

    PubMed  CAS  Google Scholar 

  • Hartsel SC, Loh WHT, Robertson LW (1983) Biotransformation of cannabidiol to cannabielsoin by suspension cultures of Cannabis sativa and Saccharum officinarum. Planta Med 48:17–19

    PubMed  CAS  Google Scholar 

  • Hendriks H, Malingre TM, Batterman S, Bos R (1978) The essential oil of Cannabis sativa L. Pharm Weekbl 113:413–424

    CAS  Google Scholar 

  • Henness S, Robinson DM, Lyseng-Williamson KA (2006) Rimonabant. Drugs 66:2109–2119

    PubMed  CAS  Google Scholar 

  • Hillig KW (2004) A chemotaxonomic analysis of terpenoid variation in Cannabis. Biochem Syst Ecol 32:875–891

    CAS  Google Scholar 

  • Hillig KW (2005) Genetic evidence for separation in Cannabis (Cannabaceae). Genet Resour Crop Evol 52:161–180

    CAS  Google Scholar 

  • Hillis WE, Inoue T (1968) The formation of polyphenols in trees-IV: the polyphenols formed in Pinus radiata after Sirex attack. Phytochemistry 7:13–22

    CAS  Google Scholar 

  • Hohlfeld H, Scheel D, Strack D (1996) Purification of hydroxycinnamoyl-CoA:tyramine hydroxycinnamoyltransferase from cell-suspension cultures of Solanum tuberosum L. cv. Datura. Planta 199:166–168

    CAS  Google Scholar 

  • Huber SC, Hardin SC (2004) Numerous posttranslational modifications provide opportunities for the intricate regulation of metabolic enzymes at multiple levels. Curr Opin Plant Biol 7:318–322

    PubMed  CAS  Google Scholar 

  • Iliya I, Akao Y, Matsumoto K, Nakagawa Y, Zulfiqar A, Ito T, Oyama M, Murata H, Tanaka T, Nozawa Y, Iinuma M (2006) Growth inhibition of stilbenoids in Welwitschiaceae and Gnetaceae through induction of apoptosis in human leukemia HL60 cells. Biol Pharm Bull 29:1490–1492

    PubMed  CAS  Google Scholar 

  • Jabs T (1999) Reactive oxygen intermediates as mediators of programmed cell death in plants and animals. Biochem Pharmacol 57:231–245

    PubMed  CAS  Google Scholar 

  • Jeandet P, Douillet-Breuil AC, Bessis R, Debord S, Sbaghi M, Adrian M (2002) Phytoalexins from the Vitaceae: biosynthesis, phytoalexin gene expression in transgenic plants, antifungal activity and metabolism. J Agric Food Chem 50:2731–2741

    PubMed  CAS  Google Scholar 

  • Jiang HE, Li X, Zhao YX, Ferguson DK, Hueber F, Bera S, Wang YF, Zhao LC, Liu CJ, Li CS (2006) A new insight into Cannabis sativa (Cannabaceae) utilization from 2500-year-old Yanghai Tombs, Xinjiang, China. J Ethnopharmacol 108:414–422

    PubMed  Google Scholar 

  • Jin W, Zjawiony JK (2006) 5-alkylresorcinols from Merulius incarnates. J Nat Prod 69:704–706

    PubMed  CAS  Google Scholar 

  • Johnson JM, Lemberger L, Novotny M, Forney RB, Dalton WS, Maskarinec MP (1984) Pharmacological activity of the basic fraction of marihuana whole smoke condensate alone and in combination with delta-9-tetrahydrocannabinol in mice. Toxicol Appl Pharmacol 72:440–448

    PubMed  CAS  Google Scholar 

  • Jones TH, Brunner SR, Edwards AA, Davidson DW, Snelling RR (2005) 6-Alkylsalicylic acids and 6-alkylresorcylic acids from ants in the genus Crematogaster from Brunei. J Chem Ecol 31:407–417

    PubMed  CAS  Google Scholar 

  • Jorgensen K, Rasmussen AV, Morant M, Nielsen AH, Bjarnholt N, Zagrobelny M, Bak S, Moller BL (2005) Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Curr Opin Plant Biol 8:280–291

    PubMed  CAS  Google Scholar 

  • Kabarity A, El-Bayoumi A, Habib A (1980) C-tumours and polyploidy induced by some alkaloids of Opium and Cannabis. Cytologia 45:497–506

    CAS  Google Scholar 

  • Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, Bedalov A, Kennedy BK (2005) Susbtrate-specific activation of sirtuins by resveratrol. J Biol Chem 280:17038–17045

    PubMed  CAS  Google Scholar 

  • Kajima M, Piraux M (1982) The biogenesis of cannabinoids in Cannabis sativa. Phytochemistry 21:67–69

    CAS  Google Scholar 

  • Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U (2003) Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain. JAMA 290:1757–1762

    PubMed  CAS  Google Scholar 

  • Keller A, Leupin M, Mediavilla V, Wintermantel E (2001) Influence of the growth stage of industrial hemp on chemical and physical properties of the fibres. Ind Crops Prod 13:35–48

    CAS  Google Scholar 

  • Kettenes-van den Bosch JJ (1978) New constituents of Cannabis sativa L. and its smoke condensate. Dissertation, State Utrecht University

  • Kettenes-van den Bosch JJ, Salemink CA (1978) Cannabis XIX: oxygenated 1,2-diphenylethanes from marihuana. J R Netherlands Chem Soc 97:221–222

    CAS  Google Scholar 

  • Kim ES, Mahlberg PG (1997) Immunochemical localization of tetrahydrocannabinol (THC) in cryofixed glandular trichomes of Cannabis (Cannabaceae). Am J Bot 84:336–342

    CAS  Google Scholar 

  • Kim Y, Han MS, Lee JS, Kim J, Kim YC (2003) Inhibitory phenolic amides on lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells from Beta vulgaris var. cicla seeds. Phytother Res 17:983–985

    PubMed  CAS  Google Scholar 

  • Kimura M, Okamoto K (1970) Distribution of tetrahydrocannabinolic acid in fresh wild Cannabis. Experientia 26:819–820

    PubMed  CAS  Google Scholar 

  • Kindl H (1985) Biosynthesis of stilbenoids. In: Higuchi T (ed) Biosynthesis and biodegradation of wood components. Academic Press Inc., New York, pp 349–377

    Google Scholar 

  • King RR, Calhoun LA (2005) Characterization of cross-linked hydroxycinnamic acid amides isolated from potato common scab lesions. Phytochemistry 66:2468–2473

    PubMed  CAS  Google Scholar 

  • Klein FK, Rapoport H (1971) Cannabis alkaloids. Nature 232:258–259

    PubMed  CAS  Google Scholar 

  • Klingauf P, Beuerle T, Mellenthin A, El-Moghazy SA, Boubakir Z, Beerhues L (2005) Biosynthesis of the hyperforin skeleton in Hypericum calycinum cell cultures. Phytochemistry 66:139–145

    PubMed  CAS  Google Scholar 

  • Knoller N, Levi L, Shoshan I, Reichenthal E, Razon N, Rappaport ZH, Biegon A (2002) Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial. Crit Care Med 30:548–554

    PubMed  CAS  Google Scholar 

  • Kostecki K, Engelmeier D, Pacher T, Hofer O, Vajrodaya S, Greger H (2004) Dihydrophenanthrenes and other antifungal stilbenoids from Stemona cf. pierrei. Phytochemistry 65:99–106

    PubMed  CAS  Google Scholar 

  • Kozubek A, Tyman JHP (1999) Resorcinolic lipids, the natural non-isoprenoid phenolic amphiphiles and their biological activity. Chem Rev 99:1–25

    PubMed  CAS  Google Scholar 

  • Kuethe JT, Comins DL (2004) Asymmetric total synthesis of (+)-cannabisativine. J Org Chem 69:5219–5231

    PubMed  CAS  Google Scholar 

  • Kushima H, Shoyama Y, Nishioka I (1980) Cannabis XII: variations of cannabinoid contents in several strains of Cannabis sativa L. with leaf-age, season and sex. Chem Pharm Bull 28:594–598

    CAS  Google Scholar 

  • Lajide L, Escoubas P, Mizutani J (1995) Termite antifeedant activity in Xylopia aethiopica. Phytochemistry 40:1105–1112

    CAS  Google Scholar 

  • Lanyon VS, Turner JC, Mahlberg PG (1981) Quantitative analysis of cannabinoids in the secretory product from capitate-stalked glands of Cannabis sativa L. (Cannabaceae). Bot Gaz 142:316–319

    CAS  Google Scholar 

  • Lee KY, Sung SH, Kim YC (2006) Neuroprotective bibenzyl glycosides of Stemona tuberose roots. J Nat Prod 69:679–681

    PubMed  CAS  Google Scholar 

  • Lee SK, Lee HJ, Min HY, Park EJ, Lee KM, Ahn YH, Cho YJ, Pyee JH (2005) Antibacterial and antifungal activity of pinosylvin, a constituent of pine. Fitoterapia 76:258–260

    PubMed  CAS  Google Scholar 

  • Leiro J, Arranz JA, Fraiz N, Sanmartin ML, Quezada E, Orallo F (2005) Effects of cis-resveratrol on genes involved in nuclear factor kappa B signaling. Int Immunopharmacol 5:393–406

    PubMed  CAS  Google Scholar 

  • Lewis NG, Davin LB (1999) Lignans: biosynthesis and function. In: Barton DHR, Nakanishi K, Meth-Cohn O (eds) Comprehensive natural products chemistry, Polyketides and other secondary metabolites including fatty acids and their derivatives, vol 1. Sankawa U (ed) Elsevier Science Ltd., Oxford, UK, pp 639–712

  • Lewis GS, Turner CE (1978) Constituents of Cannabis sativa L. XIII: stability of dosage form prepared by impregnating synthetic (-)Δ9-trans-tetrahydrocannabinol on placebo Cannabis plant material. J Pharm Sci 67:876–878

    PubMed  CAS  Google Scholar 

  • Linnaeus C (1753) Species plantarum. T. I-II

  • Ma CY, Liu WK, Che CT (2002) Lignanamides and nonalkaloidal components of Hyoscyamus niger seeds. J Nat Prod 65:206–209

    PubMed  CAS  Google Scholar 

  • Ma J, Jones SH, Hecht S (2004) Phenolic acid amides: a new type of DNA strand scission agent from Piper caninum. Bioorg Med Chem 12:3885–3889

    PubMed  CAS  Google Scholar 

  • Mahlberg PG, Hammond CT, Turner JC, Hemphill JK (1984) Structure, development and composition of glandular trichomes of Cannabis sativa L. In: Rodriguez E, Healey PL, Mehta I (eds) Biology and chemistry of plant trichomes. Plenum Press, New York, pp 23–51

    Google Scholar 

  • Majak W, Bai Y, Benn MH (2003) Phenolic amides and isoquinoline alkaloids from Corydalis sempervirens. Biochem Syst Ecol 31:649–651

    CAS  Google Scholar 

  • Malingre TH, Hendriks H, Batterman S, Bos R, Visser J (1975) The essential oil of Cannabis sativa. Planta Med 28:56–61

    PubMed  CAS  Google Scholar 

  • Manthey JA, Buslig BS (1998) Flavonoids in the living system. Adv Exp Med Biol 439:1–7

    CAS  Google Scholar 

  • Martin-Tanguy J (1985) The occurrence and possible function of hydroxycinnamoyl acid amides in plants. Plant Growth Regul 3:381–399

    CAS  Google Scholar 

  • Massi P, Vaccani A, Ceruti S, Colombo A, Abbracchio MP, Parolaro D (2004) Antitumor effects of cannabidiol, a nonpsychoctive cannabinoid,on human glioma cell lines. J Pharm Exp Ther 308:838–845

    CAS  Google Scholar 

  • Matsuda LA, Lolait SJ, Brownstein M, Young A, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564

    PubMed  CAS  Google Scholar 

  • McClanahan RH, Robertson LW (1984) Biotransformation of olivetol by Syncephalastrum racemosum. J Nat Prod 47:828–834

    PubMed  CAS  Google Scholar 

  • McGarvey DJ, Croteau R (1995) Terpenoid metabolism. Plant Cell 7:1015–1026

    PubMed  CAS  Google Scholar 

  • McNeil SD, Nuccio ML, Rhodes D, Shachar-Hill Y, Hanson AD (2000) Radiotracer and computer modeling evidence that phospho-base methylation is the main route of choline synthesis in tobacco. Plant Physiol 123:371–380

    PubMed  CAS  Google Scholar 

  • McPartland JM, Mediavilla V (2002) Noncannabinoid components. In: Grothenhermen F, Russo E (eds) Cannabis and cannabinoids: pharmacology, toxicology and therapeutic potential. The Haworth Integrative Healing Press, New York, pp 401–409

    Google Scholar 

  • McPartland JM, Clarke RC, Watson DP (2000) Hemp diseases and pests: management and biological control. CABI Publishing, Wallingford, UK

    Google Scholar 

  • Mechoulam R (1970) Marihuana chemistry. Science 168:1159–1166

    PubMed  CAS  Google Scholar 

  • Mechoulam R (1988) Alkaloids in Cannabis sativa L. In: Brussi A (ed) The alkaloids, chemistry and pharmacology, vol 34. Academic Press Inc., USA, pp 77–93

    Google Scholar 

  • Mechoulam R, Ben-Shabat S (1999) From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Nat Prod Rep 16:131–143

    PubMed  CAS  Google Scholar 

  • Mechoulam R, Fride E, Di Marzo V (1998) Endocannabinoids. Eur J Pharm 359:1–18

    CAS  Google Scholar 

  • Mediavilla V, Steinemann S (1997) Essential oil of Cannabis sativa L. strains. J Int Hemp Assoc 4:82–84

    Google Scholar 

  • Meigs TE, Simoni RD (1997) Farnesol as regulator of HMG-CoA reductase degradation: characterization and role of farnesyl pyrophosphatase. Arch Biochem Biophys 345:1–9

    PubMed  CAS  Google Scholar 

  • Miller IJ, McCallum NK, Kirk CM, Peake BM (1982) The free radical oxidation of tetrahydrocannabinols. Experientia 38:230–231

    CAS  Google Scholar 

  • Molnar J, Csiszar K, Nishioka I, Shoyama Y (1986) The effects of cannabispiro compounds and tetrahydrocannabidiolic acid on the plasmid transfer and maintenance in E. coli. Acta Microbiol Hung 33:221–231

    PubMed  CAS  Google Scholar 

  • Morimoto S, Komatsu K, Taura F, Shoyama Y (1998) Purification and characterization of cannabichromenic acid synthase from Cannabis sativa. Phytochemistry 49(6):1525–1529

    PubMed  CAS  Google Scholar 

  • Morimoto S, Taura F, Shoyama Y (1999) Biosynthesis of cannabinoids in Cannabis sativa L. Curr Top Phytochem 2:103–113

    CAS  Google Scholar 

  • Morimoto S, Tanaka Y, Sasaki K, Tanaka H, Fukamizu T, Shoyama Y, Shoyama Y, Taura F (2007) Identification and characterization of cannabinoids that induce cell death through mitochondrial permeability transition in Cannabis leaf cells. J Biol Chem 282:20739–20751

    PubMed  CAS  Google Scholar 

  • Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65

    PubMed  CAS  Google Scholar 

  • Musty RE (2004) Natural cannabinoids: interactions and effects. In: Guy GW, Whittle BA, Robson PJ (eds) The medicinal uses of cannabis and cannabinoids. Pharmaceutical Press, London, UK, pp 165–204

    Google Scholar 

  • Office of Medicinal Cannabis, The Netherlands. Available from http://www.cannabisbureau.nl

  • Oliver JM, Burg DL, Wilson BS, McLaughlin JL, Geahlen RL (1994) Inhibition of mast cell FcεR1-mediated signaling and effector function by the Syk-selective inhibitor, piceatannol. J Biol Chem 269:29697–29703

    PubMed  CAS  Google Scholar 

  • Paniego NB, Zuurbier KWM, Fung SY, Van der Heijden R, Scheffer JJC, Verpoorte R (1999) Phlorisovalerophenone synthase, a novel polyketide synthase from hop (Humulus lupulus L.) cones. Eur J Biochem 262:612–616

    PubMed  CAS  Google Scholar 

  • Paris M, Boucher F, Cosson L (1975) The constituents of Cannabis sativa pollen. Econ Bot 29:245–253

    CAS  Google Scholar 

  • Pastori GM, Del Rio LA (1997) Natural senescence of pea leaves: an activated oxygen-mediated function for peroxisomes. Plant Physiol 114:411–418

    Google Scholar 

  • Pate DW (1999) The phytochemistry of Cannabis: its ecological and evolutionary implications. In: Ranalli P (ed) Advances in hemp research. Haworth Press, NY, pp 21–42

    Google Scholar 

  • Paton WDM, Pertwee RG (1973) The actions of Cannabis in man. In: Mechoulam R (ed) Marijuana: chemistry, pharmacology, metabolism and clinical effects. Academic Press, NY, pp 287–333

    Google Scholar 

  • Petri G, Oroszlan P, Fridvalszky L (1988) Histochemical detection of hemp trichomes and their correlation with the THC content. Acta Biol Hung 39:59–74

    PubMed  CAS  Google Scholar 

  • Ponchet M, Martin-Tanguy J, Marais A, Martin C (1982) Hydroxycinnamoyl acid amides and aromatic amines in the inflorescences of some Araceae species. Phytochemistry 21:2865–2869

    CAS  Google Scholar 

  • Potter D (2004) Growth and morphology of medicinal cannabis. In: Guy GW, Whittle BA, Robson PJ (eds) The medicinal uses of cannabis and cannabinoids. Pharmaceutical Press, London, UK, pp 17–54

    Google Scholar 

  • Preisig-Müller R, Gnau P, Kindl H (1995) The inducible 9,10-dihydrophenanthrene pathway: characterization and expression of bibenzyl synthase and S-adenosylhomocysteine hydrolase. Arch Biochem Biophys 317:201–207

    PubMed  Google Scholar 

  • Raharjo TJ, Chang WT, Choi YH, Peltenburg-Looman AMG, Verpoorte R (2004a) Olivetol as product of a polyketide synthase in Cannabis sativa L. Plant Sci 166:381–385

    CAS  Google Scholar 

  • Raharjo TJ, Chang WT, Verberne MC, Peltenburg-Looman AMG, Linthorst HJM, Verpoorte R (2004b) Cloning and over-expression of a cDNA encoding a polyketide synthase from Cannabis sativa. Plant Physiol Biochem 42:291–297

    PubMed  CAS  Google Scholar 

  • Raman A (1998) The Cannabis plant: botany, cultivation and processing for use. In: Brown DT (ed) Cannabis: the genus Cannabis. Harwood Academic Publishers, Amsterdam, pp 29–54

    Google Scholar 

  • Ranganathan M, D’Souza DC (2006) The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology 188:425–444

    PubMed  CAS  Google Scholar 

  • Razdan RK, Puttick AJ, Zitko BA, Handrick GR (1972) Hashish VI: conversion of (-)-Δ1(6)-tetrahydrocannabinol to (-)-Δ1(7)- tetrahydrocannabinol, stability of (-)-Δ1- and (-)-Δ1(6)- tetrahydrocannabinols. Experientia 28:121–122

    CAS  Google Scholar 

  • Reinecke T, Kindl H (1994a) Characterization of bibenzyl synthase catalyzing the biosynthesis of phytoalexins of orchids. Phytochemistry 35:63–66

    CAS  Google Scholar 

  • Reinecke T, Kindl H (1994b) Inducible enzymes of the 9,10-dihydro-phenanthrene pathway: sterile orchid plants responding to fungal infection. Mol Plant Microbe Interact 7:449–454

    CAS  Google Scholar 

  • Rhodes D, Hanson AD (1993) Quaternary ammonium and tertiary sulfonium compounds in higher plants. Annu Rev Plant Physiol Plant Mol Biol 44:357–384

    CAS  Google Scholar 

  • Robertson LW, Koh SW, Huff SR, Malhotra RK, Ghosh A (1978) Microbiological oxidation of pentyl side-chain of cannabinoids. Experientia 34:1020–1022

    PubMed  CAS  Google Scholar 

  • Ross SA, ElSohly MA (1995) Constituents of Cannabis sativa L. XXVIII a review of the natural constituents: 1980–1994. Zagazig J Pharm Sci 4:1–10

    CAS  Google Scholar 

  • Ross SA, ElSohly MA (1996) The volatile oil composition of fresh and air-dried buds of Cannabis sativa. J Nat Prod 59:49–51

    PubMed  CAS  Google Scholar 

  • Ross SA, ElSohly HN, Elkashoury EA, Elsohly MA (1996) Fatty acids of Cannabis seeds. Phytochem Anal 7:279–283

    CAS  Google Scholar 

  • Ross SA, Mehmedic Z, Murphy TP, ElSohly MA (2000) GC-MS analysis of the total Δ9-THC content of both drug- and fiber-type cannabis seeds. J Anal Tox 24:715–717

    CAS  Google Scholar 

  • Ross AB, Shepherd MJ, Schüpphaus M, Sinclair V, Alfaro B, Kamal-Eldin A, Aman P (2003) Alkylresorcinols in cereals and cereal products. J Agric Food Chem 51:4111–4118

    PubMed  CAS  Google Scholar 

  • Ross SA, ElSohly MA, Sultana GNN, Mehmedic Z, Hossain CF, Chandra S (2005) Flavonoid glycosides and cannabinoids from the pollen of Cannabis sativa L. Phytochem Anal 16:45–48

    PubMed  CAS  Google Scholar 

  • Rothschild M, Rowan MR, Fairbairn JW (1977) Storage of cannabinoids by Arctia caja and Zonocerus elegans fed on chemically distinct strains of Cannabis sativa. Nature 266:650–651

    PubMed  CAS  Google Scholar 

  • Roy B, Dutta BK (2003) In vitro lethal efficacy of leaf extract of Cannabis sativa Linn on the larvae of Chironomous samoensis Edward: an insect of public health concern. Indian J Exp Biol 41:1338–1341

    PubMed  Google Scholar 

  • Russo E (2004) History of cannabis as a medicine. In: Guy GW, Whittle BA, Robson PJ (eds) The medicinal uses of cannabis and cannabinoids. Pharmaceutical Press, London, UK, pp 1–16

    Google Scholar 

  • Sakakibara I, Ikeya Y, Hayashi K, Okada M, Maruno M (1995) Three acyclic bis-phenylpropane lignanamides from fruits of Cannabis sativa. Phytochemistry 38:1003–1007

    PubMed  CAS  Google Scholar 

  • Schultz K, Kuehne P, Häusermann UA, Hesse M (1997) Absolute configuration of macrocyclic spermidine alkaloids. Chirality 9:523–528

    CAS  Google Scholar 

  • Segelman AB, Segelman FP, Varma S (1976) Cannabis sativa (marijuana) IX: lens aldose reductase inhibitory activity of certain marijuana flavonoids. J Nat Prod 39:475

    Google Scholar 

  • Segelman AB, Segelman FP, Star AE, Wagner H, Seligmann O (1978) Structure of two C-diglycosylflavones from Cannabis sativa. Phytochemistry 17:824–826

    CAS  Google Scholar 

  • Shine WE, Loomis WD (1974) Isomerization of geraniol and geranyl phosphate by enzymes from carrot and peppermint. Phytochemistry 13:2095–2101

    CAS  Google Scholar 

  • Shirley BW (1996) Flavonoid biosynthesis: “new” functions for and a “old” pathway. Trends Plant Sci 1:377–382

    Google Scholar 

  • Shoyama Y, Nishioka I (1978) Cannabis, XIII: two new spiro-compounds, cannabispirol and acetyl cannabispirol. Chem Pharm Bull 26:3641–3646

    CAS  Google Scholar 

  • Shoyama Y, Yagi M, Nishioka I (1975) Biosynthesis of cannabinoid acids. Phytochemistry 14:2189–2192

    CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Shoyama Y, Takeuchi A, Taura F, Tamada T, Adachi M, Kuroki R, Shoyama Y, Morimoto S (2005) Crystallization of Δ1-tetrahydrocannabinolic acid (THCA) synthase from Cannabis sativa. Acta Cryst 61:799–801

    Google Scholar 

  • Sirikantaramas S, Morimoto S, Shoyama Y, Ishikawa Y, Wada Y, Shoyama Y, Taura F (2004) The gene controlling marijuana psychoactivity; molecular cloning and heterologous expression of Δ1-tetrahydrocannabinolic acid synthase from Cannabis sativa L. J Biol Chem 279:39767–39774

    PubMed  CAS  Google Scholar 

  • Sirikantaramas S, Taura F, Tanaka Y, Ishikawa Y, Morimoto S, Shoyama Y (2005) Tetrahydrocannabinolic acid synthase, the enzyme controlling marijuana psychoactivity, is secreted into the storage cavity of the glandular trichomes. Plant Cell Physiol 46:1578–1582

    PubMed  CAS  Google Scholar 

  • Skaltsa H, Verykokidou E, Harvala C, Karabourniotis G, Manetas Y (1994) UV-B protective potential and flavonoid content of leaf hairs of Quercus ilex. Phytochemistry 37:987–990

    CAS  Google Scholar 

  • Slatkin DJ, Doorenbos NJ, Harris LS, Masoud AN, Quimby M., Schiff PLJ (1971) Chemical constituents of Cannabis sativa L. root. J Pharm Sci 60:1891–1892

    PubMed  CAS  Google Scholar 

  • Smith RM (1997) Identification of butyl cannabinoids in marijuana. J Forensic Sci 42:610–618

    CAS  Google Scholar 

  • Southon IW, Buckingham J (1989) Dictionary of alkaloids, vol I–II. Chapman & Hill Ltd., London

    Google Scholar 

  • Stahl E, Kunde R (1973) Die leitsubstanzen der Haschisch-Suchhunde. Kriminalistik 9:385–388

    Google Scholar 

  • Stivala L.A, Savio M, Carafoli F, Perucca P, Bianchi L, Magas G, Forti L, Pagnoni UM, Albini A, Prosperi E, Vannini V J (2001) Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. Biol Chem 276:22586–22594

    CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Sweetlove LJ, Fernie AR (2005) Regulation of metabolic networks: understanding metabolic complexity in the systems biology era. New Phytol 168:9–24

    PubMed  CAS  Google Scholar 

  • Tabor H, Rosenthal SM, Tabor CW (1958) The biosynthesis of spermidine and spermine from putrescine and methionine. J Biol Chem 233:907–914

    PubMed  CAS  Google Scholar 

  • Tanaka H, Takahashi R, Morimoto S, Shoyama Y (1997) A new cannabinoid, Δ6-tetrahydrocannabinol 2′-O-β-D-glucopyranoside, biotransformed by plant tissue. J Nat Prod 60:168–170

    CAS  Google Scholar 

  • Tanaka H, Shoyama Y (1999) Monoclonal antibody against tetrahydrocannabinolic acid distinguishes Cannabis sativa samples from different plant species. Forensic Sci Int 106:135–146

    PubMed  CAS  Google Scholar 

  • Taura F, Morimoto S, Shoyama Y, Mechoulam R (1995a) First direct evidence for the mechanism of Δ1-tetrahydrocannabinolic acid biosynthesis. J Am Chem Soc 117:9766–9767

    CAS  Google Scholar 

  • Taura F, Morimoto S, Shoyama Y (1995b) Cannabinerolic acid, a cannabinoid from Cannabis sativa. Phytochemistry 39:457–458

    CAS  Google Scholar 

  • Taura F, Morimoto S, Shoyama Y (1996) Purification and characterization of cannabidiolic acid synthase from Cannabis sativa L. J Biol Chem 271:17411–17416

    PubMed  CAS  Google Scholar 

  • Taura F, Sirikantaramas S, Shoyama Y, Yoshikai K, Shoyama Y, Morimoto S (2007) Cannabidiolic-acid synthase, the chemotype-determining enzyme in the fiber-type Cannabis sativa. FEBS Lett 581:2929–2934

    PubMed  CAS  Google Scholar 

  • Thakur GA, Duclos RIJ, Makriyannis A (2005) Natural cannabinoids: templates for drug discovery. Life Sci 78:454–466

    PubMed  CAS  Google Scholar 

  • Turner CE, ElSohly MA (1979) Constituents of Cannabis sativa L. XVI: a possible decomposition pathway of Δ9-tetrahydrocannabinol to cannabinol. J Heterocyclic Chem 16:1667–1668

    Article  CAS  Google Scholar 

  • Turner CE, ElSohly MA, Boeren EG (1980) Constituents of Cannabis sativa L. XVII: a review of the natural constituents. J Nat Prod 43:169–243

    PubMed  CAS  Google Scholar 

  • Turner CE, Mole ML (1973) Chemical components of Cannabis sativa. JAMA 225:639

    PubMed  CAS  Google Scholar 

  • Uy R, Wold F (1977) Posttranslational covalent modification of proteins. Science 198:890–896

    PubMed  CAS  Google Scholar 

  • Valenzano DR, Terzibasi E, Genade T, Cattneo A, Domenici L, Cellerino A (2006) Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 16:296–300

    PubMed  CAS  Google Scholar 

  • Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rössner S (2005) Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 365:1389–1397

    PubMed  Google Scholar 

  • Vanhoenacker G, Van Rompaey P, De Keukeleire D, Sandra P (2002) Chemotaxonomic features associated with flavonoids of cannabinoid-free Cannabis (Cannabis sativa subsp. sativa L.) in relation to hops (Humulus lupulus L.). Nat Prod Lett 16:57–63

    PubMed  CAS  Google Scholar 

  • Vastano BC, Chen Y, Zhu N, Ho CT, Zhou Z, Rosen RT (2000) Isolation and identification of stilbenes in two varieties of Polygonum cuspidatum. J Agric Food Chem 48:253–256

    PubMed  CAS  Google Scholar 

  • Velasco G, Galve-Roperh I, Sanchez C, Blazquez C, Haro A, Guzman M (2005) Cannabinoids and ceramide: two lipids acting hand-by-hand. Life Sci 77:1723–1731

    PubMed  CAS  Google Scholar 

  • Vree TB, Breimer DD van Ginneken CAM, van Rossum JM (1972) Identification in hashish of tetrahydrocannabinol, cannabidiol and cannabinol analogues with a methyl side-chain. J Pharm Pharmacol 24:7–12

    PubMed  CAS  Google Scholar 

  • Voirin B, Bayet C, Colson M (1993) Demonstration that flavone aglycones accumulate in the peltate glands of Mentha x piperita leaves. Phytochemistry 34:85–87

    CAS  Google Scholar 

  • Ward RS (1999) Lignans, neolignans and related compounds. Nat Prod Rep 16:75–96

    CAS  Google Scholar 

  • Wahby I, Arraez-Roman D, Segura-Carretero A, Ligero F, Caba JM, Fernandez-Gutierrez A (2006) Analysis of choline and atropine in hairy root cultures of Cannabis sativa L. by capillary electrophoresis-electrospray mass spectrometry. Electrophoresis 27:2208–2215

    PubMed  CAS  Google Scholar 

  • Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I (2007) Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci 80:1415–1419

    PubMed  CAS  Google Scholar 

  • Werker E (2000) Trichome diversity and development. Adv Bot Res 31:1–35

    Google Scholar 

  • Wills S (1998) Cannabis use and abuse by man: an historical perspective. In: Brown DT (ed) Cannabis: the genus Cannabis. Harwood Academic Publishers, Amsterdam, pp 1–27

    Google Scholar 

  • Winkel-Shirley B (1999) Evidence for enzyme complexes in the phenylpropanoid and flavonoid pathways. Physiol Plant 107:142–149

    CAS  Google Scholar 

  • Wollenweber W (1980) The systematic implication of flavonoids secreted by plants. In: Rodriguez E, Healey PL, Mehta I (eds) Biology and chemistry of plant trichomes. Plenum Press, New York, pp 53–69

    Google Scholar 

  • Yamada M, Hayashi K, Hayashi H, Ikeda S, Hoshino T, Tsutsui K, Tsutsui K, Iinuma M, Nozaki H (2006) Stilbenoids of Kobresia nepalensis (Cyperaceae) exhibiting DNA topoisomerase II inhibition. Phytochemistry 67:307–313

    PubMed  CAS  Google Scholar 

  • Yu M, Facchini PJ (1999) Purification, characterization and immunolocalization of hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl) transferase from opium poppy. Planta 209:33–44

    PubMed  CAS  Google Scholar 

  • Yusuf I, Yamaoka K, Otsuka H, Yamasaki K, Seyama I (1992) Block of sodium channels by tyramine and its analogue (N-feruloyl tyramine) in frog ventricular myocytes. Jpn J Physiol 42:179–191

    PubMed  CAS  Google Scholar 

  • Zheng XQ, Nagai C, Ashihara H (2004) Pyridine nucleotide cycle and trigonelline (N-methylnicotinic acid) synthesis in developing leaves and fruits of Coffea arabica. Physiol Plant 122:404–411

    CAS  Google Scholar 

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Acknowledgements

I. J. Flores Sanchez received a grant from CONACYT, Mexico.

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Flores-Sanchez, I.J., Verpoorte, R. Secondary metabolism in cannabis. Phytochem Rev 7, 615–639 (2008). https://doi.org/10.1007/s11101-008-9094-4

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