Postep w badaniach nad wykorzystaniem surowcow roslinnych w terapii uzaleznienia alkoholowego

• Autorzy: Mikolajczak P

Warianty tytułu

EN

Progress in studies on medicinal herbs use in treatment of alcohol dependence

• Języki publikacji: PL

Abstrakty

PL

W ostatnich latach wzrasta zainteresowanie farmakoterapią pozwalającą zwiększyć skuteczność leczenia uzależnienia alkoholowego. Pojawienie się możliwości wykorzysta­nia środków pochodzenia roślinnego, które mają zdolność zmniejszania ilości wypijanego alkoholu, wydaje się obiecujące. Ostatnio duże zainteresowanie wzbudzają takie rośliny jak dziurawiec (Hypericum peforatum L.), ołownik łatkowaty — kudzu (Pueraria lobata), iboga (Tabernanthe iboga) czy szałwia czerwonokorzeniowa (Salvia miltiorrhiza Bunge.). Ekstrakt dziurawca ma zdolność hamowania picia alkoholu u zwierząt o genetycznie uwa­runkowanej preferencji do picia alkoholu. Efekt ten jest niezależny od działania przeci- wdepresyjnego dziurawca i jest prawdopodobnie wynikiem wpływu na zmiany aktywności układu dopaminergicznego. Podawanie wyciągu z korzenia kudzu może zmniejszać picie alkoholu z wolnego wyboru u gryzoni wykazujących preferencję do etanolu. Mechanizm działania kudzu zachodzi najprawdopodobniej w wątrobie i polega na hamowaniu me­tabolizmu serotoniny lub dopaminy w mitochondriach, chociaż dokładny mechanizm nie jest jeszcze poznany. Znane są efekty hamowania picia alkoholu u szczurów preferujących ibogainę (alkaloid indolowy z Tabernanthe iboga) oraz jej nietoksyczny analog — 18- metoksykoronardynę. Z kolei ekstrakt z korzenia szałwi czerwonokorzeniowej zmniejsza konsumpcję etanolu przez hamowanie wchłaniania alkoholu z przewodu pokarmowego lub hamowania objawów zespołu odstawienia alkoholowego u szczurów poprzez wpływ GABAa u szczurów. Należy podkreślić, iż opublikowane badania kliniczne, pomimo wielo­letniej historii stosowania tych roślin jako potencjalnych środków w leczeniu uzależnienia od alkoholu, są nieliczne, a ich wyniki niejednoznaczne.

EN

In recent years there has been increasing concern for the use of pharmacotherapy to im­prove effectiveness of alcoholism treatment. Therefore, findings in the field of medicinal herbs shown to be effective in reducing alcohol intake have raised interest. Recently, such medicinal plants as extracts of St. John's wort (Hypericum peforatum L.), kudzu (Pueraria lobata), ¡boga (Tabernanthe iboga) or roots of Salvia miltiorrhiza Bunge have drawn attention as potential antialcoholic agents. The extract of the common plant Hypericum peforatum L. may suppress voluntary alcohol intake in different strains of genetically selected alcohol- preferring animals. It has been shown that the effect of the extract is independent from its antidepressant-like activity and is related to its potential to affect the dopaminergic system. Use of kudzu, particularly its extracts from Pueraria radix, is effective in reducing alcohol intake in ethanol-preferring strains of rodents. The mechanism of kudzu action is not fully understood, although it was proposed that the liver mitochondrial monoaminooxidase : aldehyde dehydrogenase 2 pathway is involved in the activity of Pueraria lobata leading to decreased serotonin and/or dopamine metabolism. It is also known that ibogaine (one of the indole alkaloids from Tabernanthe iboga) and its nontoxic analog (18-methoxycoronar- dine) may reduce alcohol intake in ethanol preferring rats. Salvia miltiorrhiza extract has been demonstrated to decrease voluntary ethanol intake by lowering alcohol absorption from gastrointestinal tract and to minimize the withdrawal symptoms via GABAa in rats. It should be stressed that published clinical studies on treatment with the plants discussed above have for a long time been scarce and the results are often equivocal.

Słowa kluczowe

PL

surowce roslinne; rosliny lecznicze; choroby czlowieka; zastosowanie; wykorzystanie; leczenie; kudzu; uzaleznienie od alkoholu; dziurawiec; szalwia czerwonokorzeniowa; iboga

• Wydawca: -
• Czasopismo: Herba Polonica
• Rocznik: 2006
• Tom: 52
• Numer: 4
• Opis fizyczny: s.133-145,bibliogr.

Twórcy

autor

Mikolajczak P

• Akademia Medyczna im.K.Marcinkowskiego w Poznaniu, ul.Rokietnicka 5a, 60-806 Poznan

Bibliografia

• 1. www.parpa.pl/download/rozdziall_2002.pdf—Sprawozdanie Rządu Rzeczpospolitej Polskiej, 13.11.2003Ocena Realizacji „Ustawy o wychowaniu w trzeźwości i przeciwdziałaniu alkoholizmowi" oraz „Narodowego Programu Profilaktyki i Rozwiązywania Problemów alkoholowych" w 2002.
• 2. Melibruda J. Psycho-bio-spoleczny model uzależnienia od alkoholu. Alkoholizm i Narkomania 1997; 3:277-82.
• 3. VetulaniJ. Uzależnienia lekowe na przełomie wieków. In Bijak M, Lasoń W, eds. Neuropsychofarmakologia Dziś i Jutro. Kraków. Instytut Farmakologii PAN, 2000:263-332.
• 4. Kranzler HR. Pharmacotherapy of alcoholism: Gaps in knowledge and opportunities for research. Alcohol Alcohol 2000; 35:537-47.
• 5. Anton RF. Pharmacologic approaches to the management of alcoholism. J Clin Psychiatry 2001; 62 (Suppl. 20):11-7.
• 6. O'Leary G, Borrow J, Weiss RD. Opioid antagonists in the treatment of alcohol dependence. Curr Psychiatry Rep 2001; 3:484-8.
• 7. Rosenberg H, Meiville J, McLean PC. Acceptability and availability of pharmacological interventions for substance misuse by British NHS treatment services. Addiction 2002; 97:59-65.
• 8. Hammarberg A, Wennberg P, Beck O, FranckJ. A comparison of two intensities of psychological intervention for alcohol dependent patients treated with acamprosate. Alcohol Alcohol 2004; 39:251-5.
• 9. Kenna CA, McGeary JE, Swift RM. Pharmacotherapy, pharmacogenomics, and the future of alcohol dependence treatment, part 1, part 2. Am J Health Syst Pharm 2004; 61:2272-8, 2380-8.
• 10. Pelc I, Hanak C, Baert I, Houtain C, Lehert P, Landron F, Verbanck P. Effect of community nurse follow-up when treating alcohol dependence with acamprosate. Alcohol Alcohol 2005; 40:302-7.
• 11. Verheul R, Lehert P, Ceerlings PJ, Koeter MWJ, van der Brink W. Predictors of acamprosate efficacy: results from a pooled analysis of seven European trials including 1485 alcohol-dependent patients. Psychopharmacology 2005; 178:167-73.
• 12. Koob CF, Roberts AJ, Schulteis C, Parsons LH, Heyser CJ, Hyytia P, Merlo-Pich E, Weiss T. Neurocircuitry targets in ethanol reward and dependence. Alcohol Clin Exp Res 1998; 22:3-9.
• 13. Addolorato C, Leggio L, Abenavoli L, Gasbarrini C. Neurobiochemical and clinical aspects of craving in alcohol addiction: a review. Addict Behav 2005; 30:1209-24.
• 14. Habrat B. Leki stosowane w leczeniu uzależnienia od alkoholu. Alkoholizm i Narkomania 2001; 14:137-49.
• 15. Lesch OM, Riegler A, Gutierrez K, Hertling I, Ramskogler K, Semler B, Zoghlami A, Benda N, Walter H. The European acamprosate trials: Conclusions for research and therapy. J Biomed Sei 2001; 8:89-95.
• 16. Mason BJ. Treatment of alcohol-dependent outpatients with acamprosate: A clinical review. J Clin Psychiatry 2001; 62: suppl. 20,42-8.
• 17. Mason BJ. Acamprosate. Recent Dev Alcohol 2003; 16:203-15.
• 18. Oveman GP, Tetr CJ, Guthrie SK. Acamprosate for adjunctive treatment of alcohol dependence. Ann Pharmacother 2003; 37:1090-9.
• 19. Kiefer F, Wiedemann K. Combined therapy: what does acamprosate and naltrexone combination tell us? Alcohol Alcohol 2004; 39:542-7.
• 20. Kirtize-Topor P, Huas D, Rosenzweig C, Comte S, Paille F, Lehert P. (2004) A pragmatic trial of acamprosate in the treatment of alcohol dependence in primary care. Alcohol Alcohol 2004; 39:520-7.
• 21. Boothby LA, Doering PL. Acamprosate for the treatment of alcohol dependence. Clin Ther 2005; 27:695-714.
• 22. Rubio G, Ponce G, Jimenez RJimenez-Arriero MA, HoenickaJ, Palomo T. Clinical predictors of response to naltrexone in alcoholic patients: Who benefits most from treatment with naltrexone? Alcohol Alcohol 2005; 40:227-33.
• 23. Wu J-Y, Jin H, SchlossJV, Fairnan MD, Ningaraj NS, Foos T, Chen W. Neurotoxic effect of acamprosate, N-acetyl-homotaurine, in cultured neurons. J Biomed Sei 2001; 8:96-103.
• 24. Dahchour A, De Witte Ph. Ethanol and amino acids in the central nervous system: assessment of the pharmacological actions of acamprosate. Prog Neurobiol 2000; 60:343-62.
• 25. Johnson BA, Ait-Daoud N. Neuropharmacological treatments for alcoholism: scientific basis and clinical findings. Psychopharmacology 2000; 149:327-44.
• 26. Harris BR, Prendergast MA, Gibson DA, Rogers DT, Blanchard JA, Holley RC, Fu MC, Hart SR, Pedigo NW, Littleton JM. Acamprosate inhibits the binding and neurotoxic effects oftrans-ACPD, suggesting a novel site of action at metabotropic glutamate receptors. Alcohol Clin Exp Res 2002; 26:1779-93.
• 27. Olive MF. Interactions between taurine and ethanol in the central nervous system. AminoAcids 2002; 223:345-57.
• 28. Harris BR, Gibson DA, Prendergast MA, Blanchard JA, Holley RC, Hart SR, Scotland RL, Foster TC, Pedigo NW, Littleton JM. The neurotoxicity induced by ethanol withdrawal in mature organotypic hippocampal slices might involve cross-talk between metabotropic glutamate type 5 receptors and N-methyl-D- aspartate receptors. Alcohol Clin Exp Res 2003; 27:1724-35.
• 29. Cano-Cebrian MJ, Zornoza-Sabina T, Guerri C, Polache A, Granero L. Acamprosate blocks the increase in dopamine extracellular levels in nucleus accumbens evoked by chemical stimulation of the ventral hippocampus. Naunyn Schmiedebergs Arch Pharmacol 2003; 368:324-7.
• 30. NagyJ, Horvath C, Farkas S, Kolok S, Szombathelyi Z. NR2B subunit selective NMDA antagonists inhibit neurotoxic effect of alcohol-withdrawal in primary cultures of rat cortical neurons. Neurochem Int 2004; 44:17-23.
• 31. Pierrefiche O, Daoust M, Naassila M. Biphasic effect of acamprosate on NMDA but not on GABAa receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratory network. Neuropharmacology 2004; 47:35-45.
• 32. Sepulveda J, Oliva P, Contreras E. Neurochemical changes of the extracellular concentrations of glutamate and aspartate in the nucleus accumbens of rats after chronic administration of morphine. Eur J Pharmacol 2004; 483:249-58.
• 33. Spanagel R, Pendyala G, Abarca C, Zghoul T, Sanchis-Segura C, Magnone MC, Lascorz J, Depner M, Holzberg D, Soyka M, Schreiber S, Matsuda F, Lathrop M, Schumann G, Albrecht U. The dock gene Per2 influences the glutamatergic system and modulates alcohol consumption. Nat Med 2005; 11:35-42.
• 34. O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and copying skills therapy for alcohol dependence: a controlled study. Arch Gen Psychiatry 1992; 49:881-7.
• 35. Volpicelli JR, Alterman AI, Hayashida M, O'Brien CP. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 1992; 49:876-80.
• 36. Ziółkowski M, Rybakowski J. Znaczenie naltreksonu w leczeniu uzależnienia alkoholowego. Farmakoterapia w Psychiatrii i Neurologii 1999; 3:10-7.
• 37. Sinclair JD. Evidence about the use of naltrexone and for different ways of using it in the treatment of alcoholism. Alcohol Alcohol 2001; 36:2-10.
• 38. Ghozland S, Chu K, Kieffer BL, Roberts A J Lack of stimulant and anxiolytic-like effects of ethanol and accelerated development of ethanol dependence in mu-opioid receptor knockout mice. Neuropharmacology 2005; 49:493-501.
• 39. Lee YK, Park SW, Kim YK, Kim DJ, Jeong J, Myrick H, Kim YH. Effects of naltrexone on the ethanol- induced changes in the rat central dopaminergic system. Alcohol Alcohol 2005; 40:297-301.
• 40. Cloninger CR. Neurogenetic adaptive mechanisms in alcoholism. Science 1987; 236:410-6.
• 41. Cloninger CR, Sigvardsson S, Gilligan SB, von-Knorring AL, Reich T, Bohman M. Genetic heterogeneity and the classification of alcoholism. Adv Alcohol Substance Abuse 1988; 7:3-16.
• 42. Windle M, Scheit DM. Alcoholic subtypes: are two sufficient? Addiction 2004; 99:1508-19.
• 43. Cardoso JMN, Barbosa A, Ismail F, Pombo S. Neter Alcoholic Typology (NAT). Alcohol Alcohol 2006; 41:133-9.
• 44. Dodd PR, Foley PF, Buckley ST, Eckert AL, Innés DJ. Genes and gene expression in the brain of the alcoholic. Addict Behav 2004; 29:1295-309.
• 45. Worst TJ, Vrana KE. Alcohol and gene expression in the central nervous system. Alcohol Alcohol 2005; 40:63-75.
• 46. Rubio G, Jimmenez-Arriero MA, Ponce G, Palomo T. Naltrexone versus acamprosate: one year follow-up of alcohol dependence treatment. Alcohol Alcohol 2001; 36:419-25.
• 47. Carai MAM, Agabio R, Bombardelli E, BourovJ, Cessa GL, Lobina C, Morazzoni P, Pani M, Reali R, Vacca G, Colombo G. Potential use of medicinal plants in the treatment of alcoholism. Fitoterapia 2000; 71: Suppl. 1, S38-S42.
• 48. Rezvani AH, Overstreet DH, Perfumi M, Massi M. Plant derivatives in the treatment of alcohol dependency. Pharmacol Biochem Behav 2003; 75:593-606.
• 49. Keung WM. Anti-dipsotropic isoflavones: the potential therapeutic agents for alcohol dependence. Med Res Rev 2003; 23:669-96.
• 50. Overstreet DH, Keung WM, Rezvani AH, Massi-And M, Lee DY. Herbal remedies for alcoholism promises and possible pitfalls. Alcohol Clin Exp Res 2003; 27:177-85.
• 51. Rezvani AH, Overstreet DH, Yang Y, Clark E. Attenuation of alcohol intake by extract of Hypericum perforatum (St. John's Wort) in two different strains of rats. Alcohol Alcohol 1999; 34:699-705.
• 52. Panocka I, Perfumi M, Angeletti S, Ciccocioppo R, Massi M. Effects of Hypericum perforatum extract on ethanol intake and behavioral despair: a search for the neurochemical systems involved. Pharmacol Biochem Behav 2000; 66:105-11.
• 53. De Vry J, Maurel S, Schreiber R, de Beun R, Jentzsch KR. Comparison of hypericum extracts with imipramine and fluoxetine in animal models of depression and alcoholism. Eur Neuropsychopharmacol 1999; 9:461-8.
• 54. Perfumi M, Ciccocioppo R, Angeletti S, Cucculelli M, Massi M. Effect of Hypericum perforatum extract on alcohol intake in Marchigian Sardinian alcohol-preferring rats. Alcohol Alcohol 1999; 34:690-8.
• 55. Perfumi M, Santoni M, Cippitelli A, Ciccocioppo R, Froldi R, Massi M. Hypericum perforatum C02 extract and opioid receptor antagonists act synergistically to reduce ethanol intake in alcohol-preferring rats. Alcohol Clin Exp Res 2003; 27:1554-62.
• 56. Perfumi M, Mattioli L, Fořti L, Massi M, Ciccocioppo R. Effect of Hypericum perforatum CO, extract on the motivational properties of ethanol alcohol-preferring rats. Alcohol Alcohol 2005; 40:291-6.
• 57. Perfumi M, Mattioli L, Cuccuelli M, Massi M. Reduction of ethanol intake by chronic treatment with Hypericum perforatum, alone or combined with naltrexone in rats. J Psychopharmacol 2005; 19:448-54.
• 58. Wright CW, Cott M, Grayson B, Hanna M.Smith AG, Sunter A, NeullJC. Correlation of hyperforin content of Hypericum perforatum (St John's Wort) extracts with their effects on alcohol drinking in C57B1V6J mice: a preliminary study. J Psychopharmacol 2003; 17:403-8.
• 59. Butterweck V, Nahrstedt A, Evans J, Hufeisen S, Rauser L, SavageJ, Popadak B, Ernsberger P, Roth BL. In vitro receptor screening of pure constituents of St. John's wort reveals novel interactions with a number of GPCRs. Psychopharmacology 2002; 162:193-202.
• 60. Keung WM, Lazo 0, Kunze L, Vallee BL. Daidzin suppresses alcohol consumption by Syrian golden hamsters without blocking acetaldehyde metabolism. Proc Natl Acad Sei USA 1995; 92:8990-3.
• 61. Overstreet DH, Lee Y-W, Rezvani AH, Pei Y-H, Criswell HE, Janowsky DS. Suppression of alcohol intake after administration of the Chinese herbal medicine, NP1-028, and its derivatives. Alcohol Clin Exp Res 1996; 20:221-7.
• 62. Overstreet DH, Lee DYW, Chen YT, Rezvani AH. The Chinese herbal medicine NPI-028 suppresses alcohol intake in alcohol-preferring rats and monkeys without taste aversion. Perfusion 1998; 11:381-90.
• 63. Keung WM, Vallee BL. Daidzin and daidzein suppress free-choice ethanol intake by Syrian golden hamsters. Proc Natl Acad Sei USA 1993; 90:10008-12.
• 64. McBridge W, Li T-K, Deitrich R, Zimarkin S, Smith BR, Rodd-Henricks ZA. Involvement of acetaldehyde in alcohol addiction. Alcohol Clin Exp Res 2002; 26:114-9.
• 65. Keung WM, Lazo O, Kunze L, Vallee BL. Potentiation of the bioavailability by an extract of Radix puerariae. Proc Natl Acad Sei USA 1996; 95:4284-8.
• 66. Lin RC, Guthrie S, Xie C-Y, Mai K, Lee DY, Lumeng L, Li T-K. Isoflavonoid compounds extracted from Pueraria iobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism. Alcohol Clin Exp Res 1996; 20:659-63.
• 67. Jang M-H, Shin M-C, Lee T-H, Bahn G-H, Shin H-S, Lim S, Kim E-H, Kim C-J. Effect of Puerariae radix on c-fos expression in hippocampus of alcohol-intoxicated juvenile rats. Biol Pharm Bull 2003; 26:37^40.
• 68. Bliss TVP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993; 361:31-9.
• 69. Bo J, Ming BY, Gang LZ, Lei C, Jia AL. Protection by puerarin against MPP+-induced neurotoxicity in PC12 cells mediated by inhibiting mitochondrial dysfunction and caspase-3-like activation. Neurosci Res 2005; 53:183-8.
• 70. Benlhabib E, Baker Jl, Keyler DE, Singh AK. Kudzu root extract suppresses voluntary intake and alcohol withdrawal symptoms in P rats receiving free access to water and alcohol. J Med Food 2004; 7:168-79.
• 71. Lee JS. Supplementation of Pueraria radix water extract on changes of antioxidant enzymes and lipid profile in ethanol-treated rats. Clin Chim Acta 2004; 347:121-8.
• 72. Popik P, Leyer RT, Skolnick P. 100 years of ibogaine: neurochemical and pharmacological actions of a putative antiaddictive drug. Pharmacol Rev 1995; 47:235-53.
• 73. Vastag B. Ibogaine therapy: A 'Vast uncontrolled experiment'. Science 2005; 308:345-6.
• 74. Rezvani AH, Overstreet DH, Lee Y-W. Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats. Pharmacol Biochem Behav 1995; 52:615-20.
• 75. He DY, McGough NN, Ravindranathan A, Jeanblanc J, Logrip ML, Phamluong K, Janak PH, Ron D. Glial cell line-derived neurotrophic factor mediates the desirable actions of the anti-addiction drug ibogaine against alcohol consumption. J Neurosci 2005; 25:619-28.
• 76. Rezvani AH, Overstreet DH, Ying Y, Banarage UK, Kuehne ME, Maisonneuve IM, Glick SD. Attenuation of alcohol consumption by a novel non-toxic ibogaine analog (18-methoxycoronaridine) in alcohol- preferring rats. Pharmacol Biochem Behav 1997; 58:615-19.
• 77. Maisonneuve IM, Glick SD. Anti-addictive actions of an ¡boga alkaloid congener : a novel mechanism for a novel treatment. Pharmacol Biochem Behav 2003; 75:607-18.
• 78. Pace CJ, Glick SD, Maisonneuve IM, He LWJokiel PA, Kuehne M, Fleck MW. Novel ¡boga alkaloid congeners block nicotinic receptors and reduce drug self-administration. EurJ Pharmacol 2004; 492:159-67.
• 79. Zubaran C, Shoaib M, Stolerman IP, Pablo J, Mash DC. Noribogaine generalization to the ibogaine stimulus: correlation with noribogaine concentration in rat brain. Neuropsychopharmacology 1999; 21:119-26.
• 80. Baumann MH, Rithman RB, Pablo JP, Mash DC. In vivo neurobiological effects of ibogaine and its 0- desmethyl metabolite, 12-hydroxyibogamine (noribogaine). J Pharmacol Exp Ther 2001; 297:531-9.
• 81. Solviter RS, Drust EC, Damoano RP, ConnerJD. A common mechanism for lysergic acid, indolealkylamine and phenethylamine hallucinogens: serotonergic mediation of behavioral effects in rats. J Pharmacol Exp Ther 1980;214:231-8.
• 82. Maisonneuve IM, Keller RW, Glick SD. Interaction between ibogaine, a potential anti-additive agent and morphine: an in-vivo microdialysis study. Eur J Pharmacol 1991; 199:35-42.
• 83. Glick SD, Rossman K, Wang S, Dong N, Keller RW. Local effects of ibogaine on extracellular levels of dopamine and its metabolites in nucleus accumbens and striatum: interaction with d-amphetamine. Brain Res 1993; 628:201-8.
• 84. Glick SD, Kuehne ME, Maisonneuve IM, Banarage UK, Molinari HH. 18-methoxycoronaridine, a novel non-toxic iboga alkaloid congener: effects on morphine and cocaine self administration and on mesolimbic dopamine release in rats. Brain Res 1996; 719:29-35.
• 85. Glick SD, Maisonneuve IS. Mechanisms of antiaddictive actions of ibogaine. Ann N Y Acad Sei 1998; 844:214-26.
• 86. Deechar CD, Teitler M, Soderlund DM, Bornmann WG, Kuehne ME, Glick SD. Mechanism of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Res 1992; 571:242-7.
• 87. Reid M, Hsu K, Broderick P, Berger SP. Evidence that ibogaine inhibits dopamine release via a kappa receptor mechanism. Abstracts. Soc Neurosci 1994; 20:1676.
• 88. Broderick P, Phelan FT, Berger SP. Ibogaine alters cocaine-induced biogenic amine and psychostimulant dysfunction but not [3H]GBR-1234 binding to the dopamine transporter protein. NIDA Res Monogr 1992; 119:285.
• 89. TaraschenkoOD, Pamchal V, Maisonneuve IM, Glick SD. Is antagonism ofalpha3beta4 nicotinic receptors a strategy to reduce morphine dependence? EurJ Pharmacol 2005; 513:207-18.
• 90. Colombo G, Agabio R, Libina C, Reali R, Morazzoni P, Bombardelli E, Gessa GL. Salvia miltiorrhiza extra« inhibits alcohol absorption, preference and discrimination in sP rats. Alcohol 1999; 18:65-70.
• 91. Brunetti G, Serra S, Vacca G, Lobina C, Morazzoni P, Bombardelli E, Colombo G, Gessa GL, Carai MAM. IDN 5982, a standardized extract of Salvia miltiorrhiza, delays acquisition of alcohol drinking behavior in rats. J Ethnopharmacol 2003; 85:93-7.
• 92. Serra S, Vacca G, Tumatis S, Carrucciu A, Morazzoni P, Bombardelli E, Colombo G, Gessa GL, Carai MAM. Anti-relapse properties of IDN 5982, a standardized extract of Salvia miltiorrhiza, in alcohol-preferring rats. J Ethnopharmacol 2003; 88:249-52.
• 93. Vacca G, Colombo G, Brunetti G, Melis S, Molinari D, Serra S, Seghizzi R, Morazzoni P, Bombardelli E, Gessa GL, Carai MSA. Reducing effect of Salvia milthiorrhiza extracts on alcohol intake: influence of vehicle. Phytother Res 2003; 17:537^11.
• 94. Mostallino MC., Mascia MP., Pisu MG., Busonero F, Talani G, Biggio G. Inhibition by miltirone of up- regulation of GABAa receptor a, subunit mRNA by ethanol withdrawal in hippocampal neurons. EurJ Pharmacol 2004; 494:83-90.
• 95. KrylovAA, IbatovAN. Experience with hypericum herbal infusion in complex treatment of patients with alcoholism in association with ulcer disease and chronic gastritis. Lik Sprava 1993; 29:115-29.
• 96. ShebeckJ, Rindone JP. A pilot study exploring the effect of kudzu root on the drinking habits of patients with chronic alcoholism. J Altern Complement Med 2000; 6:45-8.
• 97. Lukas SE, Penetar D, Berko J, Vicens L, Palmer C, Mallya G, Macklin EA, Lee DYW. An extract of the Chinese herbal root kudzu reduces alcohol drinking by heavy drinkers in a naturalistic setting. Alcohol Clin Exp Res 2005; 29:756-62.