Abstract
Conventional substance abuse treatments have had only limited success. As a result, new approaches, including vaccination to block the effects of drugs such as cocaine, nicotine, methamphetamine, and phencyclidine, are in development. Although a number of possible rationales for the effects of antidrug vaccines have been suggested, the most straightforward and intuitive mechanism would involve binding of the drug by antibodies in the blood-stream, thereby blocking entry or reducing the rate of entry of the drug into the central nervous system. The theoretical parameters that would influence vaccine-induced drug pharmacodynamics are presented in this review, along with the current status on vaccine development for nicotine, cocaine, methamphetamine, and phencyclidine.
Article PDF
Similar content being viewed by others
References and Recommended Reading
National Survey on Drug Use and Health: National Findings. Substance Abuse and Mental Health Services Administration, Office of Applied Studies website, http://www.drugabusestatistics.samhsa.gov/. Accessed June 25, 2007.
EMCDDA annual report 2006. European Monitoring Centre for Drugs and Drug Addiction website. http://www.emcdda.europa.eu/. Accessed June 25, 2007.
Mitchell JM, Tavares VC, Fields HL, et al.: Endogenous opioid blockade and impulsive responding in alcoholics and healthy controls. Neuropsychopharmacology 2007, 32:439–449.
Sinclair JD, Alho H, Shinderman M: Naltrexone for alcohol dependence. N Engl J Med 2002, 346:1329–1331. Author reply 1329–1331.
Johnson BA: A synopsis of the pharmacological rationale, properties and therapeutic effects of depot preparations of naltrexone for treating alcohol dependence. Expert Opin Pharmacother 2006, 7:1065–1073.
Jenkins AJ, Keenan RM, Henningfield JE, Cone EJ: Correlation between pharmacological effects and plasma cocaine concentrations after smoked administration. J Anal Toxicol 2002, 26:382–392.
Cook CE, Jeffcoat AR, Hill JM, et al.: Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride. Drug Metab Dispos 1993, 21:717–723.
Day ED: Advanced Immunochemistry, edn 2. New York: Wiley-Liss; 1990.
Gentry WB, Laurenzana EM, Williams DK, et al.: Safety and efficiency of an anti-(+)-methamphetamine monoclonal antibody in the protection against cardiovascular and central nervous system effects of (+)-methamphetamine in rats. Int Immunopharmacol 2006, 6:968–977.
Eisen HN: Immunology, edn 2. New York: Harper & Row; 1980.
Eisen HN, Siskind GW: Variations in affinities of antibodies during the immune response. Biochemistry 1964, 3:996–1008.
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.
Barbet J, Rougon-Rapuzzi G, Cupo A, Delaage MA: Structural requirements for recognition of vasopressin by antibody; thermodynamic and kinetic characteristics of the interaction. Mol Immunol 1981, 18:439–446.
Smith TW, Skubitz KM: Kinetics in interactions between antibodies and haptens. Biochemistry 1975, 14:1496–1502.
Balster RL, Schuster CR: Fixed-interval schedule of cocaine reinforcement: effect of dose and infusion duration. J Exp Anal Behav 1973, 20:119–129.
Fox BS, Kantak KM, Edwards MA, et al.: Efficacy of a therapeutic cocaine vaccine in rodent models. Nat Med 1996, 2:1129–1132.
Matsushita M, Hoffman TZ, Ashley JA, et al.: Cocaine catalytic antibodies: the primary importance of linker effects. Bioorg Med Chem Lett 2001, 11:87–90.
Laurenzana EM, Byrnes-Blake KA, Milesi-Halle A, et al.: Use of anti-(+)-methamphetamine monoclonal antibody to significantly alter (+)-methamphetamine and (+)-amphetamine disposition in rats. Drug Metab Dispos 2003, 31:1320–1326.
Perez-Stable EJ, Herrera B, Jacob P, 3rd, Benowitz NL: Nicotine metabolism and intake in black and white smokers. JAMA 1998, 280:152–156.
Keyler DE, Hieda Y, St Peter J, Pentel PR: Altered disposition of repeated nicotine doses in rats immunized against nicotine. Nicotine Tob Res 1999, 1:241–249.
Keyler DE, Roiko SA, Benlhabib E, et al.: Monoclonal nicotine-specific antibodies reduce nicotine distribution to brain in rats: dose-and affinity-response relationships. Drug Metab Dispos 2005, 33:1056–1061.
Pentel PR, Dufek MB, Roiko SA, et al.: Differential effects of passive immunization with nicotine-specific antibodies on the acute and chronic distribution of nicotine to brain in rats. J Pharmacol Exp Ther 2006, 317:660–666.
Williams RH, Maggiore JA, Shah SM, et al.: Cocaine and its major metabolites in plasma and urine samples from patients in an urban emergency medicine setting. J Anal Toxicol 2000, 24:478–481.
Jufer RA, Wstadik A, Walsh SL, et al.: Elimination of cocaine and metabolites in plasma, saliva, and urine following repeated oral administration to human volunteers. J Anal Toxicol 2000, 24:467–477.
Tobacco use in America. Substance Abuse and Mental Health Services Administration, Office of Applied Studies website. http://www.oas.samhsa.gov/NHSDA/tobacco/chapter1.htm. Accessed June 25, 2007.
Fiore MC, Bailey MC, Cohen SJ, et al.: Treating tobacco use and dependence. http://www.surgeongeneral.gov/tobacco/treating_tobacco_use.pdf. Accessed June 2007.
Hieda Y, Keyler DE, Ennifar S, et al.: Vaccination against nicotine during continued nicotine administration in rats: immunogenicity of the vaccine and effects on nicotine distribution to brain. Int J Immunopharmacol 2000, 22:809–819.
Hieda Y, Keyler DE, Vandevoort JT, et al.: Immunization of rats reduces nicotine distribution to brain. Psychopharmacology (Berl) 1999, 143:150–157.
Pentel PR, Malin DH, Ennifar S, et al.: A nicotine conjugate vaccine reduces nicotine distribution to brain and attenuates its behavioral and cardiovascular effects in rats. Pharmacol Biochem Behav 2000, 65:191–198.
Sobue S, Sekiguchi K, Kikkawa H, et al.: Comparison of nicotine pharmacokinetics in healthy Japanese male smokers following application of the transdermal nicotine patch and cigarette smoking. Biol Pharm Bull 2006, 29:1068–1073.
Maurer P, Jennings GT, Willers J, et al.: A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity. Eur J Immunol 2005, 35:2031–2040.
Bunce CJ, Loudon PT, Akers C, et al.: Development of vaccines to help treat drug dependence. Curr Opin Mol Ther 2003, 5:58–63.
Heading CE: Drug evaluation: CYT-002-NicQb, a therapeutic vaccine for the treatment of nicotine addiction. Curr Opin Investig Drugs 2007, 8:71–77.
Haney M, Kosten TR: Therapeutic vaccines for substance dependence. Expert Rev Vaccines 2004, 3:11–18.
Martell BA, Mitchell E, Poling J, et al.: Vaccine pharmacotherapy for the treatment of cocaine dependence. Biol Psychiatry 2005, 58:158–164.
Carrera MR, Ashley JA, Parsons LH, et al.: Suppression of psychoactive effects of cocaine by active immunization. Nature 1995, 378:727–730.
Carrera MR, Ashley JA, Zhou B, et al.: Cocaine vaccines: antibody protection against relapse in a rat model. Proc Natl Acad Sci U S A 2000, 97:6202–6206.
Kantak KM, Collins SL, Lipman EG, et al.: Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model. Psychopharmacology (Berl) 2000, 148:251–262.
Kosten TR, Rosen M, Bond J, et al.: Human therapeutic cocaine vaccine: safety and immunogenicity. Vaccine 2002, 20:1196–1204.
Deng SX, Bharat N, Fischman MC, Landry DW: Covalent modification of proteins by cocaine. Proc Natl Acad Sci U S A 2002, 99:3412–3416.
Proksch JW, Gentry WB, Owens SM: Anti-phencyclidine monoclonal antibodies provide long-term reductions in brain phencyclidine concentrations during chronic phencyclidine administration in rats. J Pharmacol Exp Ther 2000, 292:831–837.
Valentine JL, Owens SM: Antiphencyclidine monoclonal antibody therapy significantly changes phencyclidine concentrations in brain and other tissues in rats. J Pharmacol Exp Ther 1996, 278:717–724.
Hardin JS, Wessinger WD, Proksch JW, Owens SM: Pharmacodynamics of a monoclonal antiphencyclidine Fab with broad selectivity for phencyclidine-like drugs. J Pharmacol Exp Ther 1998, 285:1113–1122.
Valentine JL, Mayersohn M, Wessinger WD, et al.: Antiphencyclidine monoclonal Fab fragments reverse phencyclidine-induced behavioral effects and ataxia in rats. J Pharmacol Exp Ther 1996, 278:709–716.
McMillan DE, Hardwick WC, Li M, et al.: Effects of murine-derived anti-methamphetamine monoclonal antibodies on (+)-methamphetamine self-administration in the rat. J Pharmacol Exp Ther 2004, 309:1248–1255.
Byrnes-Blake KA, Laurenzana EM, Landes RD, et al.: Monoclonal IgG affinity and treatment time alters antagonism of (+)-methamphetamine effects in rats. Eur J Pharmacol 2005, 521:86–94.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Orson, F.M., Kinsey, B.M., Singh, R.A.K. et al. The future of vaccines in the management of addictive disorders. Curr Psychiatry Rep 9, 381–387 (2007). https://doi.org/10.1007/s11920-007-0049-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11920-007-0049-z