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. 2006 Mar 24;8(1):E174–E184. doi: 10.1208/aapsj080121

Symbiotic relationship of pharmacogenetics and drugs of abuse

Joni L Rutter 1,✉
PMCID: PMC2751437  PMID: 16584126

Abstract

Pharmacogenetics/pharmacogenomics is the study of how genetic variation affects pharmacology, the use of drugs to treat disease. When drug responses are predicted in advance, it is easier to tailor medications to different diseases and individuals. Pharmacogenetics provides the tools required to identify genetic predictors of probable drug response, drug efficacy, and drug-induced adverse events—identifications that would ideally precede treatment decisions. Drug abuse and addiction genetic data have advanced the field of pharmacogenetics in general. Although major findings have emerged, pharmacotherapy remains hindered by issues such as adverse events, time lag to drug efficacy, and heterogeneity of the disorders being treated. The sequencing of the human genome and high-throughput technologies are enabling pharmacogenetics to have greater influence on treatment approaches. This review highlights key studies and identifies important genes in drug abuse pharmacogenetics that provide a basis for better diagnosis and treatment of drug abuse disorders.

Keywords: Pharmacogenomics, addiction, treatment, psychiatric disease, SNP

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References

  • 1.Uhl GR, Grow RW. The burden of complex genetics in brain disorders. Arch Gen Psychiatry. 2004;61:223–229. doi: 10.1001/archpsyc.61.3.223. [DOI] [PubMed] [Google Scholar]
  • 2.Lichtermann D, Franke P, Maier W, Rao ML. Pharmacogenomics and addiction to opiates. Eur J Pharmacol. 2000;410:269–279. doi: 10.1016/S0014-2999(00)00820-7. [DOI] [PubMed] [Google Scholar]
  • 3.Berrettini W, Bierut L, Crowley T, et al. Letter—Setting priorities for genomic research. Science. 2004;304:1445–1447. doi: 10.1126/science.304.5676.1445c. [DOI] [PubMed] [Google Scholar]
  • 4.Goldman D, Oroszi G, Ducci F. The genetics of addictions: uncovering the genes. Nat Rev Genet. 2005;6:521–532. doi: 10.1038/nrg1635. [DOI] [PubMed] [Google Scholar]
  • 5.Lessov CN, Swan GE, Ring HZ, Khroyan TV, Lernan C. Genetics and drug use as a complex phenotype. Subst Use Misuse. 2004;39:1515–1569. doi: 10.1081/JA-200033202. [DOI] [PubMed] [Google Scholar]
  • 6.Hall WD. Will nicotine genetics and a nicotine vaccine prevent cigarette smoking and smoking-related diseases? PLoS Med. 2005;2:e266–e266. doi: 10.1371/journal.pmed.0020266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Merikangas KR, Risch N. Setting priorities for genomic research. Science. 2003;302:599–601. doi: 10.1126/science.1091468. [DOI] [PubMed] [Google Scholar]
  • 8.Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286:487–491. doi: 10.1126/science.286.5439.487. [DOI] [PubMed] [Google Scholar]
  • 9.Miksys S, Tyndale RF. Drug-metabolizing cytochrome P450s in the brain. J Psychiatry Neurosci. 2002;27:406–415. [PMC free article] [PubMed] [Google Scholar]
  • 10.Peto R. Smoking and death: the past 40 years and the next 40. BMJ. 1994;309:937–939. doi: 10.1136/bmj.309.6959.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Benowitz NL. Drug therapy: pharmacologic aspects of cigarette smoking and nicotine addiction. N Engl J Med. 1988;319:1318–1330. doi: 10.1056/NEJM198811173192005. [DOI] [PubMed] [Google Scholar]
  • 12.Bjartveit K, Tverdal A. Health consequences of smoking 1–4 cigarettes per day. Tob Control. 2005;14:315–320. doi: 10.1136/tc.2005.011932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Kawachi I, Colditz GA, Stampfer MJ, et al. Smoking cessation and time course of decreased risks of coronary heart disease in middle-agred women. Arch Intern Med. 1994;154:169–175. doi: 10.1001/archinte.1994.00420020075009. [DOI] [PubMed] [Google Scholar]
  • 14.Rosengren A, Wilhelmsen L, Wedel H. Coronary heart disease, cancer and mortality in middle-aged light smokers. J Intern Med. 1992;231:357–362. doi: 10.1111/j.1365-2796.1992.tb00944.x. [DOI] [PubMed] [Google Scholar]
  • 15.Prescott E, Scharling H, Osler M, et al. Importance of light smoking and inhalation habits on risk of myocardial infarction and all cause mortality: a 22-year follow-up of 12,149 men and women in the Copenhagen city heart study. J Epidemiol Community Health. 2002;56:702–706. doi: 10.1136/jech.56.9.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Shiffman S, Fischer LB, Zettler-Segal M, Benowitz NL. Nicotine exposure among nondependent smokers. Arch Gen Psychiatry. 1990;47:333–336. doi: 10.1001/archpsyc.1990.01810160033006. [DOI] [PubMed] [Google Scholar]
  • 17.Ellickson PL, McCaffrey DF, Ghosh-Dastidar B, Longshore DL. New inroads in preventing adolescent drug use: results from a largescale trial of project ALERT in middle schools. Am J Public Health. 2003;93:1830–1836. doi: 10.2105/AJPH.93.11.1830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Hall W, Madden P, Lynskey M. The genetics of tobacco use: methods, findings and policy implications. Tob Control. 2002;11:119–124. doi: 10.1136/tc.11.2.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Tyndale RF. Genetics of alcohol and tobacco use in humans. Ann Med. 2003;35:94–121. doi: 10.1080/07853890310010014. [DOI] [PubMed] [Google Scholar]
  • 20.Li MD, Cheng R, Ma JZ, Swan GE. A meta-analysis of estimated genetic and environmental effects on smoking behavior in male and female adult twins. Addiction. 2003;98:23–31. doi: 10.1046/j.1360-0443.2003.00295.x. [DOI] [PubMed] [Google Scholar]
  • 21.Bierut LJ, Rice JP, Edenberg HJ, et al. Family-based study of the association of the dopamine D2 receptor gene (DRD2) with habitual smoking. Am J Med Genet. 2000;90:299–302. doi: 10.1002/(SICI)1096-8628(20000214)90:4<299::AID-AJMG7>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
  • 22.Comings DE, Ferry L, Bradshaw-Robinson S, Burchette R, Chiu C, Muhleman D. The dopamine D2 receptor (DRD2) gene: a genetic risk factor in smoking. Pharmacogenetics. 1996;6:73–79. doi: 10.1097/00008571-199602000-00006. [DOI] [PubMed] [Google Scholar]
  • 23.Beuten J, Ma JZ, Payne TJ, et al. Single- and multilocus allelic variants within the GABAB receptor subunit 2 (GABAB2) gene are significantly associated with nicotine dependence. Am J Hum Genet. 2005;76:859–864. doi: 10.1086/429839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Vandenbergh DJ, Kozlowski LT, Bennett CJ, et al. DAT's not all, but it may be more than we realize. Nicotine Tob Res. 2002;4:251–252. doi: 10.1080/14622200210141248. [DOI] [PubMed] [Google Scholar]
  • 25.Lerman C, Shields PG, Audrain J, et al. The role of the serotonin transporter gene in cigarette smoking. Cancer Epidemiol Biomarkers Prev. 1998;7:253–255. [PubMed] [Google Scholar]
  • 26.Shields PG, Lerman C, Audrain J, et al. Dopamine D4 receptors and the risk of cigarette smoking in African-Americans and Caucasians. Cancer Epidemiol Biomarkers Prev. 1998;7:453–458. [PubMed] [Google Scholar]
  • 27.Sabol SZ, Nelson ML, Fisher C, et al. A genetic association for cigarette smoking behavior. Health Psychol. 1999;18:7–13. doi: 10.1037/0278-6133.18.1.7. [DOI] [PubMed] [Google Scholar]
  • 28.Sullivan PF, Jiang Y, Neale MC, Kendler KS, Straub RE. Association of the tryptophan hydroxylase gene with smoking initiation but not progression in nicotine dependence. Am J Med Genet. 2001;105:479–484. doi: 10.1002/ajmg.1433. [DOI] [PubMed] [Google Scholar]
  • 29.Swan GE, Valdes AM, Ring HZ, et al. Dopamine receptorDRD2 genotype and smoking cessation outcome following treatment with bupropion SR. Pharmacogenomics J. 2005;5:21–29. doi: 10.1038/sj.tpj.6500281. [DOI] [PubMed] [Google Scholar]
  • 30.McKinney EF, Walton RT, Yudkin P, et al. Association between polymorphisms in dopamine metabolic enzymes and tobacco consumption in smokers. Pharmacogenetics. 2000;10:483–491. doi: 10.1097/00008571-200008000-00001. [DOI] [PubMed] [Google Scholar]
  • 31.Neville MJ, Johnstone EC, Walton RT. Identification and characterization ofANKK1: a novel kinase gene closely linked toDRD2 on chromosome band 11q23.1. Hum Mutat. 2004;23:540–545. doi: 10.1002/humu.20039. [DOI] [PubMed] [Google Scholar]
  • 32.Kreek MJ, Bart G, Lilly C, Laforge KS, Nielsen DA. Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments. Pharmacol Rev. 2005;57:1–26. doi: 10.1124/pr.57.1.1. [DOI] [PubMed] [Google Scholar]
  • 33.Xie W, Altamirano CV, Bartels CF, Speirs RJ, Cashman JR, Lockridge O. An improved cocaine hydrolase: the A328Y mutant of human butyrylcholinesterase is 4-fold more efficient. Mol Pharmacol. 1999;55:83–91. doi: 10.1124/mol.55.1.83. [DOI] [PubMed] [Google Scholar]
  • 34.Mogil JS, Miermeister F, Seifert F, et al. Variable senstivity to noxious heat is mediated by differential expression of theCGRP gene. Proc Natl Acad Sci USA. 2005;102:12938–12943. doi: 10.1073/pnas.0503264102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Owens JC, Balogh SA, McClure-Begley TD, et al. Alpha 4 beta 2* nicotinic acetylcholine receptors modulate the effects of ethanol and nicotine on the acoustic startle response. Alcohol Clin Exp Res. 2003;27:1867–1875. doi: 10.1097/01.ALC.0000102700.72447.0F. [DOI] [PubMed] [Google Scholar]
  • 36.Cohen C, Kodas E, Griebel G. CB1 receptor antagonists for the treatment of nicotine addiction. Pharmacol Biochem Behav. 2005;81:387–395. doi: 10.1016/j.pbb.2005.01.024. [DOI] [PubMed] [Google Scholar]
  • 37.Castane A, Berrendero F, Maldonado R. The role of the cannabinoid system in nicotine addiction. Pharmacol Biochem Behav. 2005;81:381–386. doi: 10.1016/j.pbb.2005.01.025. [DOI] [PubMed] [Google Scholar]
  • 38.Zubieta JK, Heitzeg MM, Smith YR, et al. COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003;299:1240–1243. doi: 10.1126/science.1078546. [DOI] [PubMed] [Google Scholar]
  • 39.Li T, Chen CK, Hu X, et al. Association analysis of the DRD4 and COMT genes in methamphetamine abuse. Am J Med Genet B Neuropsychiatr Genet. 2004;129:120–124. doi: 10.1002/ajmg.b.30024. [DOI] [PubMed] [Google Scholar]
  • 40.Vandenbergh DJ, Rodriguez LA, Hivert E, et al. Long forms of the dopamine receptor (DRD4) gene VNTR are more prevalent in substance abusers: no interaction with functional alleles of the catechol-o-methyltransferase (COMT) gene. Am J Med Genet. 2000;96:678–683. doi: 10.1002/1096-8628(20001009)96:5<678::AID-AJMG15>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  • 41.Tyndale RF, Sellers EM. Variable CYP2A6-mediated nicotine metabolism alters smoking behavior and risk. Drug Metab Dispos. 2001;29:548–552. [PubMed] [Google Scholar]
  • 42.Pianezza ML, Sellers EM, Tyndale RF. Nicotine metabolism defect reduces smoking. Nature. 1998;393:750–750. doi: 10.1038/31623. [DOI] [PubMed] [Google Scholar]
  • 43.Gelernter J, Kranzler HR, Satel SL, Rao PA. Genetic association between dopamine transporter protein alleles and cocaine-induced paranoia. Neuropsychopharmacology. 1994;11:195–200. doi: 10.1038/sj.npp.1380106. [DOI] [PubMed] [Google Scholar]
  • 44.Fuke S, Suo S, Takahashi N, Koike H, Sasagawa N, Ishiura S. The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression. Pharmacogenomics J. 2001;1:152–156. doi: 10.1038/sj.tpj.6500026. [DOI] [PubMed] [Google Scholar]
  • 45.Lott DC, Kim S-J, Cook EH, de Wit H. Dopamine transporter gene associated with diminished subjective response to amphetamine. Neuropsychopharmacology. 2005;30:602–609. doi: 10.1038/sj.npp.1300637. [DOI] [PubMed] [Google Scholar]
  • 46.Stein MA, Waldman ID, Sarampote CS, et al. Dopamine transporter genotype and methylphenidate dose response in children with ADHD. Neuropsychopharmacology. 2005;30:1374–1382. doi: 10.1038/sj.npp.1300787. [DOI] [PubMed] [Google Scholar]
  • 47.Chen R, Han DD, Gu HH. A triple mutation in the second transmembrane domain of mouse dopamine transporter markedly decreases sensitivity to cocaine and methylphenidate. J Neurochem. 2005;94:352–359. doi: 10.1111/j.1471-4159.2005.03199.x. [DOI] [PubMed] [Google Scholar]
  • 48.Lerman C, Jepson C, Wileyto EP, et al. Role of Functional Genetic Variation in the Dopamine D2 Receptor (DRD2) in Response to bupropion and Nicotine Replacement Therapy for Tobacco Dependence: Results of Two Randomized Clinical Trials. Neuropsychopharmacology. 2006;31:231–242. doi: 10.1038/sj.npp.1300861. [DOI] [PubMed] [Google Scholar]
  • 49.Xu K, Lichtermann D, Lipsky RH, et al. Association of specific haplotypes of D2 dopamine receptor gene with vulnerability to heroin dependence in 2 distinct populations. Arch Gen Psychiatry. 2004;61:597–606. doi: 10.1001/archpsyc.61.6.597. [DOI] [PubMed] [Google Scholar]
  • 50.Noble EP, Zhang X, Ritchie TL, Sparkes RS. Haplotypes at the DRD2 locus and severe alcoholism. Am J Med Genet. 2000;96:622–631. doi: 10.1002/1096-8628(20001009)96:5<622::AID-AJMG7>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]
  • 51.Gelernter J, Kranzler H. D2 dopamine receptor gene (DRD2) allele and haplotype frequencies in alcohol dependent and control subjects: no association with phenotype or severity of phenotype. Neuropsychopharmacology. 1999;20:640–649. doi: 10.1016/S0893-133X(98)00110-9. [DOI] [PubMed] [Google Scholar]
  • 52.Sander T, Ladehoff M, Samochowiec J, Finckh U, Rommelspacher H, Schmidt LG. Lack of an allelic association between polymorphisms of the dopamine D2 receptor gene and alcohol dependence in the German population. Alcohol Clin Exp Res. 1999;23:578–581. doi: 10.1111/j.1530-0277.1999.tb04157.x. [DOI] [PubMed] [Google Scholar]
  • 53.Gelernter J, Kranzler H, Satel SL. No association between D2 dopamine receptor (DRD2) alleles or haplotypes and cocaine dependence or severity of cocaine dependence in European- and African-Americans. Biol Psychiatry. 1999;45:340–345. doi: 10.1016/S0006-3223(97)00537-4. [DOI] [PubMed] [Google Scholar]
  • 54.Goldman D, Urbanek M, Guenther D, Robin R, Long JC. Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism, substance abuse and schizophrenia in Southwestern American Indians. Am J Med Genet. 1997;74:386–394. doi: 10.1002/(SICI)1096-8628(19970725)74:4<386::AID-AJMG9>3.0.CO;2-N. [DOI] [PubMed] [Google Scholar]
  • 55.Chen CK, Hu X, Lin SK, et al. Association analysis of dopamine D2-like receptor genes and methamphetamine abuse. Psychiatr Genet. 2004;14:223–226. doi: 10.1097/00041444-200412000-00011. [DOI] [PubMed] [Google Scholar]
  • 56.Chang FM, Ko HC, Lu RB, Pakstis AJ, Kidd KK. The dopamine D4 receptor gene (DRD4) is not associated with alcoholism in three Taiwanese populations: six polymorphisms tested separately and as haplotypes. Biol Psychiatry. 1997;41:394–405. doi: 10.1016/S0006-3223(96)00248-X. [DOI] [PubMed] [Google Scholar]
  • 57.Nishiyama T, Ikeda M, Iwata N, et al. Haplotype association between GABAA receptor gamma2 subunit gene (GABRG2) and methamphetamine use disorder. Pharmacogenomics J. 2005;5:89–95. doi: 10.1038/sj.tpj.6500292. [DOI] [PubMed] [Google Scholar]
  • 58.Hashimoto T, Hashimoto K, Matsuzawa D, et al. A functional glutathioneS-transferase P1 gene polymorphism is associated with methamphetamine-induced psychosis in Japanese population. Am J Med Genet B Neuropsychiatr Genet. 2005;135:5–9. doi: 10.1002/ajmg.b.30164. [DOI] [PubMed] [Google Scholar]
  • 59.Zimniak P, Nanduri B, Pikula S, et al. Naturally occurring human glutathione S-transferase GSTP1-1 isoforms with isoleucine and valine in position 104 differ in enzymic properties. Eur J Biochem. 1994;224:893–899. doi: 10.1111/j.1432-1033.1994.00893.x. [DOI] [PubMed] [Google Scholar]
  • 60.Szumlinski KK, Abernathy KE, Oleson EB, et al. Homer isforms differentially regulate cocaine-induced neuroplasticity.Neuropsychopharmacology. 2005;14.Epub ahead of print. [DOI] [PubMed]
  • 61.Mogil JS, Ritchie J, Smith SB, et al. Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans. J Med Genet. 2005;42:583–587. doi: 10.1136/jmg.2004.027698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Mogil JS, Wilson SG, Chesler EJ, et al. The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans. Proc Natl Acad Sci USA. 2003;100:4867–4872. doi: 10.1073/pnas.0730053100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Kim H, Neubert JK, San MA, et al. Genetic influences on variability in human acute experimental pain sensitivity associated with gender, ethnicity and psychological temperament. Pain. 2004;109:488–496. doi: 10.1016/j.pain.2004.02.027. [DOI] [PubMed] [Google Scholar]
  • 64.Lerman C, Wileyto EP, Patterson F, et al. The functional muopioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial. Pharmacogenomics J. 2004;4:184–192. doi: 10.1038/sj.tpj.6500238. [DOI] [PubMed] [Google Scholar]
  • 65.Gelernter J, Kranzler H, Cubells J. Genetics of two μ opioid receptor gene (OPRM1) exon 1 polymorphisms: population studies, and allele frequencies in alcohol- and drug-dependent subjects. Mol Psychiatry. 1999;4:476–483. doi: 10.1038/sj.mp.4000556. [DOI] [PubMed] [Google Scholar]
  • 66.Bart G, Heilig M, LaForge KS, et al. Substantial attributable risk related to a functional mu-opioid receptor gene polymorphism in association with heroin addiction in central Sweden. Mol Psychiatry. 2004;9:547–549. doi: 10.1038/sj.mp.4001504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Bond C, LaForge KS, Tian M, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci USA. 1998;95:9608–9613. doi: 10.1073/pnas.95.16.9608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Befort K, Filliol D, Decaillot FM, Gaveriaux-Ruff C, Hoehe MR, Kieffer BL. A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling. J Biol Chem. 2001;276:3130–3137. doi: 10.1074/jbc.M006352200. [DOI] [PubMed] [Google Scholar]
  • 69.Beyer A, Kock T, Schroder H, Schulz S, Hollt V. Effect of the A118G polymorphism on binding affinity, potency and agonist-mediated endocytosis, desensitization, and resensitization of the human mu-opioid receptor. J Neurochem. 2004;89:553–560. doi: 10.1111/j.1471-4159.2004.02340.x. [DOI] [PubMed] [Google Scholar]
  • 70.Zhang Y, Wang D, Johnson AD, Papp AC, Sadee W. Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem. 2005;280:32618–32624. doi: 10.1074/jbc.M504942200. [DOI] [PubMed] [Google Scholar]
  • 71.Oslin DW, Berrettini W, Kranzler HR, et al. A functional polymorphism of the μ-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology. 2003;28:1546–1552. doi: 10.1038/sj.npp.1300219. [DOI] [PubMed] [Google Scholar]
  • 72.Lotsch J, Skarke C, Grosch S, Darimont J, Schmidt H, Geisslinger G. The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. Pharmacogenetics. 2002;12:3–9. doi: 10.1097/00008571-200201000-00002. [DOI] [PubMed] [Google Scholar]
  • 73.Fillingim RB, Kaplan L, Staud R, et al. The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans. J Pain. 2005;6:159–167. doi: 10.1016/j.jpain.2004.11.008. [DOI] [PubMed] [Google Scholar]
  • 74.Fiore MC. Treating tobacco use and dependence: an introduction to the US Public Health Service Clinical Practice Guideline. Respir Care. 2000;45:1196–1199. [PubMed] [Google Scholar]
  • 75.National Institute on Drug Abuse . Research Report Series: Nicotine Addiction. Bethesda, MD: NIDA; 2001. [Google Scholar]
  • 76.Fiore MC, Smith SS, Jorenby DE, Baker TB. The effectiveness of the nicotine patch for smoking cessation: a meta-analysis. JAMA. 1994;271:1940–1947. doi: 10.1001/jama.1994.03510480064036. [DOI] [PubMed] [Google Scholar]
  • 77.Paoletti P, Fornai E, Maggiorelli F, et al. Importance of baseline cotinine plasma values in smoking cessation: results from a double-blind study with nicotine patch. Eur Respir J. 1996;9:643–651. doi: 10.1183/09031936.96.09040643. [DOI] [PubMed] [Google Scholar]
  • 78.Pickworth WB, Fant RV, Butschky MF, Henningfield JE. Effects of transdermal nicotine delivery on measures of acute nicotine withdrawal. J Pharmacol Exp Ther. 1996;279:450–456. [PubMed] [Google Scholar]
  • 79.Foulds J, Burke M, Steinberg M, Williams JM, Ziedonis DM. Advances in pharmacotherapy for tobacco dependence. Expert Opin Emerg Drugs. 2004;9:39–53. doi: 10.1517/14728214.9.1.39. [DOI] [PubMed] [Google Scholar]
  • 80.Anthenelli RM. Rimonabant helps for smoking cessation, weight loss. ACC 53rd Annual Scientific Session: Late-Breaking Clinical Trials; March 9, 2004; New Orleans, LA.
  • 81.Heading CE. Nic VAX Nabi Biopharmaceuticals. IDrugs. 2003;6:1178–1181. [PubMed] [Google Scholar]
  • 82.Cerny T. Anti-nicotine vaccination: where are we now? Recent Results Cancer Res. 2005;166:167–175. doi: 10.1007/3-540-26980-0_12. [DOI] [PubMed] [Google Scholar]
  • 83.Hatsukami DK, Rennard S, Jorenby D, et al. Safety and immunogenicity of a nicotine conjugate vaccine in current smokers. Clin Pharmacol Ther. 2005;78:456–467. doi: 10.1016/j.clpt.2005.08.007. [DOI] [PubMed] [Google Scholar]
  • 84.Dale LC, Glover ED, Sachs DP, et al. Bupropion for smoking cessation: predictors of successful outcome. Chest. 2001;119:1357–1364. doi: 10.1378/chest.119.5.1357. [DOI] [PubMed] [Google Scholar]
  • 85.Merikangas KR, Stolar M, Stevens DE, et al. Familial transmission of substance use disorders. Arch Gen Psychiatry. 1998;55:973–979. doi: 10.1001/archpsyc.55.11.973. [DOI] [PubMed] [Google Scholar]
  • 86.Tsuang MT, Lyons MJ, Meyer JM, et al. Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities. Arch Gen Psychiatry. 1998;55:967–972. doi: 10.1001/archpsyc.55.11.967. [DOI] [PubMed] [Google Scholar]
  • 87.Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiology Catchment Area (ECA) study. JAMA. 1990;264:2511–2518. doi: 10.1001/jama.1990.03450190043026. [DOI] [PubMed] [Google Scholar]
  • 88.Ikeda K, Soichiro I, Han W, Hayashida M, Uhl GR, Sora I. How individual sensitivity to opiates can be predicted by gene analyses. Trends Pharmacol Sci. 2005;26:311–317. doi: 10.1016/j.tips.2005.04.001. [DOI] [PubMed] [Google Scholar]
  • 89.Ross JR, Rutter D, Welsh K, et al. Clinical response to morphine in cancer patients and genetic variation in candidate genes. Pharmacogenomics J. 2005;5:324–336. doi: 10.1038/sj.tpj.6500327. [DOI] [PubMed] [Google Scholar]
  • 90.Tiseo PJ, Thaler HT, Lapin J, Inturrisi CE, Portenoy RK, Foley KM. Morphine-6-glucuronide concentrations and opioid-related side effects: a survey in cancer patients. Pain. 1995;61:47–54. doi: 10.1016/0304-3959(94)00148-8. [DOI] [PubMed] [Google Scholar]
  • 91.MacGregor AJ, Griffiths GO, Baker J, Spector TD. Determinants of pressure pain threshold in adult twins: evidence that shared environmental influences predominate. Pain. 1997;73:253–257. doi: 10.1016/S0304-3959(97)00101-2. [DOI] [PubMed] [Google Scholar]
  • 92.Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science. 1997;277:968–971. doi: 10.1126/science.277.5328.968. [DOI] [PubMed] [Google Scholar]
  • 93.Snyder SH. Amphetamine psychosis: a “model” schizophrenia mediated by catecholamines. Am J Psychiatry. 1973;130:61–67. doi: 10.1176/ajp.130.1.61. [DOI] [PubMed] [Google Scholar]
  • 94.Sato M, Chen CC, Akiyama K, Otsuki S. Acute exacerbation of paranoid psychotic state after long-term abstinence in patients with previous methamphetamine psychosis. Biol Psychiatry. 1983;18:429–440. [PubMed] [Google Scholar]
  • 95.Volkow ND. Message from the Director on Amphetamine Abuse. Available at: http://www.nida.nih.gov/about/welcome/messagemeth405. html. Accessed February 23, 2006.
  • 96.Kendler KS, Karkowski LM, Neale MC, Prescott CA. Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins. Arch Gen Psychiatry. 2000;57:261–269. doi: 10.1001/archpsyc.57.3.261. [DOI] [PubMed] [Google Scholar]
  • 97.Tsuang MT, Lyons MJ, Eisen SA, et al. Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin pairs. Am J Med Genet. 1996;67:473–477. doi: 10.1002/(SICI)1096-8628(19960920)67:5<473::AID-AJMG6>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  • 98.Leshner AI. Addiction is a brain disease, and it matters. Science. 1997;278:45–47. doi: 10.1126/science.278.5335.45. [DOI] [PubMed] [Google Scholar]
  • 99.Merikangas KR, Risch N. Will the genomics revolution revolutionize psychiatry? Am J Psychiatry. 2003;160:625–635. doi: 10.1176/appi.ajp.160.4.625. [DOI] [PubMed] [Google Scholar]
  • 100.Croghan TW, Tomlin M, Pescosolido BA, et al. American attitudes toward and willingness to use psychiatric medications. J Nerv Ment Dis. 2003;191:166–174. doi: 10.1097/01.NMD.0000054933.52571.CA. [DOI] [PubMed] [Google Scholar]
  • 101.Nunes EV, Levin FR. Treatment of depression in patients with alcohol or other drug dependence: a meta-analysis. JAMA. 2004;291:1887–1896. doi: 10.1001/jama.291.15.1887. [DOI] [PubMed] [Google Scholar]
  • 102.Kendler KS, Jacobson KC, Prescott CA, Neale MC. Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates in male twins. Am J Psychiatry. 2003;160:687–695. doi: 10.1176/appi.ajp.160.4.687. [DOI] [PubMed] [Google Scholar]
  • 103.Bierut LJ, Rice JP, Goate A, et al. A genomic scan for habitual smoking in families of alcoholics: common and specific genetic factors in substance dependence. Am J Med Genet A. 2004;124:19–27. doi: 10.1002/ajmg.a.20329. [DOI] [PubMed] [Google Scholar]
  • 104.Frueh FW, Goodsaid F, Rudman A, Huang S-M, Lesko LJ. The need for education in pharmacogenomics: a regulatory perspective. Pharmacogenomics J. 2005;5:218–220. doi: 10.1038/sj.tpj.6500316. [DOI] [PubMed] [Google Scholar]
  • 105.Rubin DL, Thorn C, Klein TE, Altman RB. A statistical approach to scanning the biomedical literature for pharmacogenetics knowledge. J Am Med Inform Assoc. 2005;12:121–129. doi: 10.1197/jamia.M1640. [DOI] [PMC free article] [PubMed] [Google Scholar]

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