Abstract
Cannabinoids and in particular the main psychoactive Δ9-THC are promising substances forthe development of new drugs and are of high importance in biomedicine and pharmacy. This reviewgives an overview of the chemical properties of Δ9-THC, its synthesis on industrial scale, andthe synthesis of important metabolites. The biosynthesis of cannabinoids in Cannabissativa is extensively described in addition to strategies for optimization of this plantfor cannabinoid employment in medicine. The metabolism of Δ9-THC in humans is shown and, basedon this, analytical procedures for cannabinoids and their metabolites in human forensic samples aswell as in C. sativa will be discussed. Furthermore, someaspects of medicinal indications for Δ9-THC and its ways of administration are described. Finally,some synthetic cannabinoids and their importance in research and medicine are delineated.
T. Flemming and R. Muntendam both contributed equally
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References
Shulgin AT (1968) J Psychedelic Drugs 2:14
Elsohly MA, Slade D (2005) Life Sci 78:539
Pate DW (2004) In: Grotenhermen F (ed) Cannabis un Cannabinoide. Hans Huber, Bern, p 33
Garrett ER, Hunt CA (1974) J Pharm Sci 63:1056
Uliss DB, Handrick GR, Dalzell HC, Razdan RK (1978) Tetrahedron 34:1885
Gaoni Y, Mechoulam R (1971) J Am Chem Soc 93:217
Kriwacki RW, Makriyannis A (1989) Mol Pharmacol 35:495
Mechoulam R, Devane WA, Glaser R (1999) In: Nahas GG, Sutin KM, Harvey DJ, Agurell S (eds) Marihuana and medicine. Humana, New Jersey, p 65
Gaoni Y, Mechoulam R (1964) J Am Chem Soc 86:1646
Miller IJ, McCallum NK, Kirk CM, Peake BM (1982) Cell Mol Life Sci (CMLS) 38:230
Turner CE, Elsohly MA (1979) J Heterocycl Chem 16:1667
Ranalli P, Venturi G (2004) Euphytica 140:1
Collin C, Davies P, Mutiboko IK, Ratcliffe S (2007) Eur J Neurol 14:290
Ligresti A, Moriello AS, Starowicz K, Matias I, Pisanti S, De Petrocellis L, Laezza C, Portella G, Bifulco M, Di Marzo V (2006) J Pharmacol Exp Ther 318:1375
Williamson EM, Evans FJ (2000) Drugs 60:1303
Charles T, Hammond PGM (1973) Am J Botany 60:542
Turner JC, Hemphill JK, Mahlberg PG (1981) Bull Narc 33:63
Turner JC, Hemphill JK, Mahlberg PG (1981) Bull Narc 33:59
Eun-Soo Kim PGM (1997) Am J Botany 84:336
Jocelyn C, Turner JKH, Mahlberg PG (1978) Am J Botany 65:1103
Sirikantaramas S, Taura F, Tanaka Y, Ishikawa Y, Morimoto S, Shoyama Y (2005) Plant Cell Physiol 46:1578
Lange BM, Rujan T, Martin W, Croteau R (2000) Proc Natl Acad Sci USA 97:13172
Eisenreich W, Bacher A, Arigoni D, Rohdich F (2004) Cell Mol Life Sci 61:1401
Rohdich F, Kis K, Bacher A, Eisenreich W (2001) Curr Opin Chem Biol 5:535
Julsing MK, Koulman A, Woerdenbag HJ, Quax WJ, Kayser O (2006) Biomol Eng 23:265
Raharjo TJ, Chang W-T, Choi YH, Peltenburg-Looman AMG, Verpoorte R (2004) Plant Sci 166:381
Raharjo TJ, Chang WT, Verberne MC, Peltenburg-Looman AM, Linthorst HJ, Verpoorte R (2004) Plant Physiol Biochem 42:291
Fellermeier M, Eisenreich W, Bacher A, Zenk MH (2001) Eur J Biochem 268:1596
Lichtenthaler HK, Schwender J, Disch A, Rohmer M (1997) FEBS Lett 400:271
Lichtenthaler HK (1999) Annu Rev Plant Physiol Plant Mol Biol 50:47
Austin MB, Noel JP (2003) Nat Prod Rep 20:79
Fellermeier M, Zenk MH (1998) FEBS Lett 427:283
Shoyama Y, Hirano H, Nishioka I (1984) Phytochemistry 23:1909
Funa N, Ozawa H, Hirata A, Horinouchi S (2006) Proc Natl Acad Sci USA 103:6356
Kajima M, Piraux M (1982) Phytochemistry 21:67
Horper W, Marner F-J (1996) Phytochemistry 41:451
Kuzuyama T, Noel JP, Richard SB (2005) Nature 435:983
Sirikantaramas S, Morimoto S, Shoyama Y, Ishikawa Y, Wada Y, Shoyama Y, Taura F (2004) J Biol Chem 279:39767
Taura F, Morimoto S, Shoyama Y (1996) J Biol Chem 271:17411
Morimoto S, Komatsu K, Taura F, Shoyama Y (1998) Phytochemistry 49:1525
Taura F, Morimoto S, Shoyama Y, Mechoulam R (1995) J Am Chem Soc 117:9766
Taura U (2004) Research report, Graduate School of Pharmceutical Sciences, Kyushu University. Available at http://www.nisr.or.jp/englishHP/report2004/NISR04taura.pdf , last visited: 29 June 2007
Yoshikai K, Morimoto S, Shoyama Y (2001) Japanese Patent 2000–78979
Kojoma M, Seki H, Yoshida S, Muranaka T (2006) Forensic Sci Int 159:132
Cherniak L (1982) The great books of Cannabis, vol I, Book II. Damele, Oakland, CA
Hillig KW (2005) Gene Res Crop Evolut 52:1573
Pacifico D, Miselli F, Micheler M, Carboni A, Ranalli P, Mandolino G (2006) Mole Breed 17:257
Renner SS, Ricklefs RE (1995) Am J Bot 82:596
Sakamoto K, Abe T, Matsuyama T, Yoshida S, Ohmido N, Fukui K, Satoh S (2005) Genome 48:931
Sakamoto K, Akiyama Y, Fukui K, Kamada H, Satoh S (1998) Cytologica 63:459
Mandolino GAC, Bagatta MVM, Moliterni C, Ranalli P (2002) Euphytica 126:211
Mandolino G, Bagatta M, Carboni A, Ranalli P, Meijer E (2003) J Industrial Hemp 8:51
de Meijer EPM, Bagatta M, Carboni A, Crucitti P, Moliterni VMC, Ranalli P, Mandolino G (2003) Genetics 163:335
de Meijer EPM, Hammond KM (2005) Euphytica 145:189
Sharma GK (1975) Bull Torrey Bot Club 102:199
Jansen M, Gaba V, Greenberg BM (1998) Trends Plant Sci 3:131
Lydon J (1986) Effects of ultraviolet-B radiation on the growth, physiology and cannabinoid production of Cannabis sativa L. Dissertation, Maryland University, USA
Lydon J, Teramura AH, Coffman CB (1987) Photochem Photobiol 46:201
Pijlman FTA, Rigter SM, Hoek J, Goldschmidt HMJ, Niesink RJM (2005) Addiction Biol 10:171
Heitrich A, Binder M (1982) Cell Mol Life Sci 38:898
Feeney M, Punja ZK (2003) In Vitro Cell Develop Biol Plant 39:578
Braemer R, Paris M (1987) Plant Cell Reports 6:150
Koziel MG, Beland GL, Bowman C, Carozzi NB, Crenshaw R, Crossland L, Dawson J, Desai N, Hill M, Kadwell S, Launis K, Lewis K, Maddox D, McPherson K, Meghji MR, Merlin E, Rhodes R, Warren GW, Wright M, Evola SV (1993) Nat Biotech 11:194
Herbers K (2003) J Plant Physiol 160:821
Mason HS, Lam DM, Arntzen CJ (1992) Proc Natl Acad Sci USA 89:11745
Gaoni Y, Mechoulam R (1964) J Am Chem Soc 86:1646
Mechoulam R, Braun P, Gaoni Y (1972) J Am Chem Soc 94:6159
Mechoulam R, Braun P, Gaoni Y (1967) J Am Chem Soc 89:4552
Razdan RK, Handrick GR, Dalzell HC (1975) Experientia 31:16
Petrzilka T, Haefliger W, Sikemeier C (1969) Helv Chim Acta 52:1102
Razdan RK, Dalzell HC, Handrick GR (1974) J Am Chem Soc 96:5860
Mechoulam R, Lander N, University A, Zahalka J (1990) Tetrahedron: Asymmetry 1:315
Fahrenholtz KE, Lurie M, Kierstead RW (1967) J Am Chem Soc 89:5934
Archer RA, Blanchard WB, Day WA, Johnson DW, Lavagnino ER, Ryan CW, Baldwin JE (1977) J Org Chem 42:2277
Kachensky DF, Hui AHF (1997) J Org Chem 62:7065
Szirmai M (1995) Total synthesis and analysis of major human urinary metabolites of d1-tetrahydrocannabinol, the principal psychoactive component of Cannabis sativa L. Dissertation, Uppsala University, Sweden
Siegel C, Gordon PM, Razdan RK (1989) J Org Chem 54:5428
Seltzman HH, Begum KM, Wyrick DC (1991) J Labelled Compds Radiopharm 29:1009
Melvin LS, Milne GM, Johnson MR, Subramaniam B, Wilken GH, Howlett AC (1993) Mol Pharmacol 44:1008
Eissenstat MA, Bell MR, D'Ambra TE, Alexander EJ, Daum SJ, Ackerman JH, Gruett MD, Kumar V, Estep KG, Olefirowicz EM, et al. (1995) J Med Chem 38:3094
Turner CE, Elsohly MA, Boeren EG (1980) J Nat Prod 43:169
Ross SA, El-Sohly MA (1995) Zagazig J Pharm Sci 4:1
Mediavilla V, Steinemann S (1997) J Inter Hemp Assoc 4:80
Ross SA, ElSohly MA (1998) Bull Narcotics
Bacigalupo MA, Ius A, Meroni G, Grassi G, Moschella A (1999) J Agric Food Chem 47:2743
Lercker G, Bocci F, Frega N, Bortolomeazzi R (1992) Farmaco 47:367
Lehmann T, Brenneisen R (1995) J Liquid Chrom 18:689
Ross SA, Mehmedic Z, Murphy TP, Elsohly MA (2000) J Anal Toxicol 24:715
Raharjo TJ, Verpoorte R (2004) Phytochem Anal 15:79
Harvey DJ (1987) Mass Spectrom Rev 6:135
Rustichelli C, Ferioli V, Baraldi M, Zanoli P, Gamberini G (1998) Chromatographia 48:215
Hazekamp A, Peltenburg A, Verpoorte R, Giroud C (2005) J Liquid Chrom Rel Technol 28:2361
Hazekamp A, Choi YH, Verpoorte R (2004) Chem Pharm Bull 52:718
Teale JD, Forman EJ, King LJ, Piall EM, Marks V (1975) J Pharm Pharm 27:465
ElSohly MA, Jones AB, ElSohly HN (1990) J Anal Toxicol 14:277
Tanaka H, Goto Y, Shoyama Y (1996) J Immunoassay 17:321
Tanaka H, Shoyama Y (1999) Forensic Sci Int 106:135
Musshoff F, Madea B (2006) Ther Drug Monit 28:155
Brenneisen R (2004) In: Grotenhermen F (ed) Cannabis und Cannabinoide. Hans Huber, Bern, p 89
Agurell S, Halldin M, Lindgren JE, Ohlsson A, Widman M, Gillespie H, Hollister L (1986) Pharmacol Rev 38:21
Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I (2007) Life Sci 80:1415
Grotenhermen F (2003) Clin Pharmacokinet 42:327
Baptista MJ, Monsanto PV, Pinho Marques EG, Bermejo A, Avila S, Castanheira AM, Margalho C, Barroso M, Vieira DN (2002) Forensic Sci Int 128:66
Sporkert F, Pragst F (2000) Forensic Sci Int 107:129
Musshoff F, Lachenmeier DW, Kroener L, Madea B (2003) Forensic Sci Int 133:32
de Oliveira CDR, Yonamine M, de Moraes Moreau RL (2007) J Sep Sci 30:128
Boumba VA, Ziavrou KS, Vougiouklakis T (2006) Int J Toxicol 25:143
Skopp G, Potsch L (2004) J Anal Toxicol 28:35
Jamerson MH, McCue JJ, Klette KL (2005) J Anal Toxicol 29:627
Moore C, Vincent M, Rana S, Coulter C, Agrawal A, Soares J (2006) Forensic Sci Int 164:126
Kim JY, Suh SI, In MK, Paeng KJ, Chung BC (2005) Arch Pharm Res 28:1086
Nadulski T, Sporkert F, Schnelle M, Stadelmann AM, Roser P, Schefter T, Pragst F (2005) J Anal Toxicol 29:782
Jamerson MH, Welton RM, Morris-Kukoski CL, Klette KL (2005) J Anal Toxicol 29:664
Moore C, Rana S, Coulter C, Feyerherm F, Prest H (2006) J Anal Toxicol 30:171
Franski R, Tezyk A, Wachowiak R, Schroeder G (2004) J Mass Spectrom 39:458
Concheiro M, de Castro A, Quintela O, Cruz A, Lopez-Rivadulla M (2004) J Chromatogr B Analyt Technol Biomed Life Sci 810:319
Maralikova B, Weinmann W (2004) J Mass Spectrom 39:526
Teixeira H, Proenca P, Verstraete A, Corte-Real F, Vieira DN (2005) Forensic Sci Int 150:205
Kolmonen M, Leinonen A, Pelander A, Ojanpera I (2007) Anal Chim Acta 585:94
Laloup M, Ramirez Fernandez MM, Wood M, De Boeck G, Henquet C, Maes V, Samyn N (2005) J Chromatogr A 1082:15
Fisher DH, Broudy MI, Fisher LM (1996) Biomed Chromatogr 10:161
Walsh JM, Crouch DJ, Danaceau JP, Cangianelli L, Liddicoat L, Adkins R (2007) J Anal Toxicol 31:44
Clarke J, Wilson JF (2005) Forensic Sci Int 150:161
Moody DE, Fang WB, Andrenyak DM, Monti KM, Jones C (2006) J Anal Toxicol 30:50
Cirimele V, Villain M, Mura P, Bernard M, Kintz P (2006) Forensic Sci Int 161:180
Li HL (1974) Econ Bot 28:437
O'Shaughnessy WB (1838) Trans Med Phys Soc Bengal, p 71
Gaoni Y, Mechoulam R (1964) J Am Chem Soc 86:1646
Sallan SE, Zinberg NE, Frei E 3rd (1975) N Engl J Med 293:795
Palenicek JP, Graham NM, He YD, Hoover DA, Oishi JS, Kingsley L, Saah AJ (1995) J Acquir Immune Defic Syndr Hum Retrovirol 10:366
Beal JE, Olson R, Laubenstein L, Morales JO, Bellman P, Yangco B, Lefkowitz L, Plasse TF, Shepard KV (1995) J Pain Symptom Manage 10:89
Beal JE, Olson R, Lefkowitz L, Laubenstein L, Bellman P, Yangco B, Morales JO, Murphy R, Powderly W, Plasse TF, Mosdell KW, Shepard KV (1997) J Pain Symptom Manage 14:7
Brenneisen R, Egli A, Elsohly MA, Henn V, Spiess Y (1996) Int J Clin Pharmacol Ther 34:446
Maurer M, Henn V, Dittrich A, Hofmann A (1990) Eur Arch Psychiatry Clin Neurosci 240:1
Muller-Vahl KR, Schneider U, Kolbe H, Emrich HM (1999) Am J Psychiatry 156:495
Finnegan-Ling D, Musty RE (1994) Symposium on the cannabinoids, Burlington, Vermont. International Cannabinoid Research Society, p 53
Petro DJ, Ellenberger C Jr (1981) J Clin Pharmacol 21:413S
Merritt JC, McKinnon S, Armstrong JR, Hatem G, Reid LA (1980) Ann Ophthalmol 12:947
Jacob A, Todd AR (1940) J Chem Soc, p 649
Karniol IG, Carlini EA (1973) Psychopharmacologia 33:53
Jones G, Pertwee RG (1972) Br J Pharmacol 45:375
Zuardi AW, Morais SL, Guimaraes FS, Mechoulam R (1995) J Clin Psychiatry 56:485
Weiss L, Zeira M, Reich S, Har-Noy M, Mechoulam R, Slavin S, Gallily R (2006) Autoimmunity 39:143
Einhorn LH, Nagy C, Furnas B, Williams SD (1981) J Clin Pharmacol 21:64S
Aguiar AJ, Rasadi B (1983) US Patent 4406888. Pfizer, New York
Johnson MR, Melvin LS Jr(1983) US Patent 4371720. Pfizer, New York
Haubrich DR, Ward SJ, Baizman E, Bell MR, Bradford J, Ferrari R, Miller M, Perrone M, Pierson AK, Saelens JK, et al. (1990) J Pharmacol Exp Ther 255:511
D'Ambra TE, Estep KG, Bell MR, Eissenstat MA, Josef KA, Ward SJ, Haycock DA, Baizman ER, Casiano FM, Beblin NC, et al. (1992) J Med Chem 35:124
Rinaldi-Carmona M, Barth F, Millan J, Derocq JM, Casellas P, Congy C, Oustric D, Sarran M, Bouaboula M, Calandra B, Portier M, Shire D, Breliere JC, Le Fur GL (1998) J Pharmacol Exp Ther 284:644
Munjal M, ElSohly MA, Repka MA (2006) AAPS Pharm Sci Tech 7:71
van Drooge DJ, Hinrichs WL, Wegman KA, Visser MR, Eissens AC, Frijlink HW (2004) Eur J Pharm Sci 21:511
Perlin E, Smith CG, Nichols AI, Almirez R, Flora KP, Cradock JC, Peck CC (1985) J Pharm Sci 74:171
Hazekamp A, Ruhaak R, Zuurman L, Van Gerven J, Verpoorte R (2006) J Pharm Sci 95:1308
Valiveti S, Agu RU, Hammell DC, Paudel KS, Earles DC, Wermeling DP, Stinchcomb AL (2007) Eur J Pharm Biopharm 65:247
Mannila J, Jarvinen T, Jarvinen K, Tarvainen M, Jarho P (2005) Eur J Pharm Sci 26:71
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Flemming, T., Muntendam, R., Steup, C., Kayser, O. (2007). Chemistry and Biological Activity of Tetrahydrocannabinol and its Derivatives. In: Khan, M.T.H. (eds) Bioactive Heterocycles IV. Topics in Heterocyclic Chemistry, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7081_2007_084
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