Journal of Bioethical Inquiry

, Volume 15, Issue 1, pp 45–55 | Cite as

Ethical Implications in Vaccine Pharmacotherapy for Treatment and Prevention of Drug of Abuse Dependence

  • Anna Carfora
  • Paola Cassandro
  • Alessandro Feola
  • Francesco La Sala
  • Raffaella Petrella
  • Renata Borriello
Critical Perspectives


Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. “Drug vaccines” aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, “cocaine and nicotine vaccines” have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway. However, although vaccines can become a reasonable treatment option for drugs of abuse, there are several disadvantages that must be considered. These include i) great individual variability in the formation of antibodies, ii) the lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice, and iii) the lack of an effect on the drug desire that may predispose an addict to relapse. In addition, a comprehensive overview of several crucial ethical issues has not yet been widely discussed in order to have not only a biological approach to immunotherapy of addiction. Overall, immunotherapy offers a range of possible treatment options: the pharmacological treatment of addiction, the treatment of overdoses, the prevention of toxicity to the brain or the heart, and the protection of the fetus during pregnancy. So far, the results obtained from a small-scale experiment using vaccines against cocaine and nicotine suggest that a number of important technical challenges still need to be overcome before such vaccines can be approved for clinical use.


Ethical issues on immunotherapy for drugs of dependence Cocaine and nicotine vaccines Vaccines against drugs of addiction 


  1. Akbarzadeh, A., M. Mehraby, M. Zarbakhsh, and H. Farzaneh. 1999. Design and synthesis of a morphine-6-succinyl-bovine serum albumin hapten for vaccine development. Biotechnology and Applied Biochemistry 30(2): 139–145.PubMedGoogle Scholar
  2. Akbarzadeh, A., D. Norousian, A. Farhangi, et al. 2009. Immunotherapy of 347 volunteer outpatient morphine addicts by human therapeutic morphine vaccine in Kermanshah. Journal of Pharmacology and Toxicology 4: 30–35.CrossRefGoogle Scholar
  3. Alving, C.R., G.R. Matyas, O. Torres, R. Jalah, and Z. Beck. 2014. Adjuvants for vaccines to drugs of abuse and addiction. Vaccine 32(42): 5382–5389.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Anton, B., and P. Leff. 2006. A novel bivalent morphine/heroin vaccine that prevents relapse to heroin addiction in rodents. Vaccine 24(16): 3232–3240.CrossRefPubMedGoogle Scholar
  5. Anton, B., A. Salazar, A. Flores, et al. 2009. Vaccines against morphine/heroin and its use as effective medication for preventing relapse to opiate addictive behaviors. Human Vaccines 5(4): 214–229.CrossRefPubMedGoogle Scholar
  6. Ashcroft, R E., and C. Franey. 2004. Further ethical and social issues in using a cocaine vaccine: Response to Hall and Carter. Journal of Medical Ethics 30: 341–343.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Baird, T.J., S.X. Deng, D.W. Landry, G. Winger, and J.H. Woods. 2000. Natural and artificial enzymes against cocaine I. Monoclonal antibody 15A10 and the reinforcing effects of cocaine in rats. Pharmacology and Experimental Therapeutics 295(3): 1127–1134.Google Scholar
  8. Berkowitz, B., and S. Spector. 1972. Evidence for active immunity to morphine in mice. Science 178(67): 1290–1292.CrossRefPubMedGoogle Scholar
  9. Bonese, K.F., B.H. Wainer, F.W. Fitch, R.M. Rothberg, and C.R. Schuster. 1974. Changes in heroin self- administration by a rhesus monkey after morphine immunisation. Nature 252(5485): 708–710.CrossRefPubMedGoogle Scholar
  10. Bremer P.T., A. Kimishima, J. E. Schlosburg, B. Zhou, K.C. Collins, K. D. Janda. 2016. Combatting synthetic designer opioids: A conjugate vaccine ablates lethal doses of fentanyl class drugs. Angewandte Chemie International Edition 55(11): 3772–3775.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Brimijoin, S., F. Orson, T. Kosten, et al. 2013a. Anti-cocaine antibody and butyrylcholinesterase-derived cocaine hydrolase exert cooperative effects on cocaine pharmacokinetics and cocaine-induced locomotor activity in mice. Chemico-Biological Interactions 203(1): 212–216.CrossRefPubMedGoogle Scholar
  12. Brimijoin, S., X. Shen, F. Orson, and T. Kosten. 2013b. Prospects, promise and problems on the road to effective vaccines and related therapies for substance abuse. Expert Review of Vaccines 12(3): 323–332.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Byrnes-Blake, K., F. Carroll, P. Abraham, and S. Owens. 2001. Generation of anti-(+) methamphetamine antibodies is not impeded by (+) meth-amphetamine administration during active immunization of rats. International Immunopharmacology 1(2): 329–338.CrossRefPubMedGoogle Scholar
  14. Carrera, M.R.A., J.A. Ashley, L.H. Parsons, P. Wisching, G. Koob, and K.D. Janda. 1995. Suppression of psychoactive effects of cocaine by active immunization. Nature 378(6558): 727–730.CrossRefPubMedGoogle Scholar
  15. Carrera, M.R., J.M. Trigo, P. Wirsching, et al. 2005. Evaluation of the anticocaine monoclonal antibody GNC92H2 as an immunotherapy for cocaine overdose. Pharmacology biochemistry and behavior 81(4): 709–714.CrossRefGoogle Scholar
  16. Carroll, F., P. Abraham, P. Gong, et al. 2009. The synthesis of haptens and their use for the development of monoclonal antibodies for treating methamphetamine abuse. Journal of Medicinal Chemistry 52(22): 7301–7309.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Carroll, M.E., N.E. Zlebnik, J.J. Andker, et al. 2012. Combined cocaine hydrolase gene transfer and anti-cocaine vaccine synergistically block cocaine-induced locomotion. PPLoS ONE 7(8): e43536.CrossRefGoogle Scholar
  18. Cheng, L., S. Kim, A. Chung, and A. Castro. 1973. Amphetamines: new radioimmunoassay. FEBS Letters 36(3): 339–342.CrossRefPubMedGoogle Scholar
  19. Choi, M., B. Gorovitz, J. Choi, E. Song, K. Nam, and J. Park. 1994. A visual immunoassay for the detection of methamphetamine using an enzyme labeled tracer derived from methamphetamine and amphetamine. Biological and Pharmaceutical Bulletin 17(7): 875–880.CrossRefPubMedGoogle Scholar
  20. Choi, J., M. Choi, C. Kim, Y. Cho, J. Chin, and Y. Joi. 1997. The optimization of ELISA for methamphetamine determination: The effect of immunogen, tracer and antibody purification method on the sensitivity. Archives of Pharmacal Research 20(1): 46–52.CrossRefPubMedGoogle Scholar
  21. Choi, J., C. Kim, and M. Choi. 1998. Immunological analysis of methamphetamine antibody and its use for the detection of methamphetamine by capillary electrophoresis with laser-induced fluorescence. Journal of Chromatography B 705(2): 277–282.CrossRefGoogle Scholar
  22. Christakis, N.A., and J.H. Fowler. 2009. The surprising power of our social networks and how they shape our lives - How your friends’ friends’ friends affect everything you feel, think, and do. Little, Brown and Co. Hachette Book Group: New York.Google Scholar
  23. Clinical Trials 2006. NicVAX® (Nicotine Conjugate Vaccine). Accessed 10 February, 2017.
  24. Cohen, P.J. 1997. Immunization for prevention and treatment of cocaine abuse: Legal and ethical implication. Drug and Alcohol Dependence 48(3): 167–174.CrossRefPubMedGoogle Scholar
  25. Cohen, P. 2000. No more kicks. New Scientist 166(2242): 23–36.Google Scholar
  26. Ersche, K., P.S. Jones, G.B. Williams, A.J. Turton, T.W. Robbins, and E.T. Bullmore. 2012. Abnormal brain structure implicated in stimulant drug addiction. Science 335(6068): 601–604.CrossRefPubMedGoogle Scholar
  27. European Medicines Agency, EMA. 2004. . Accessed February 10, 2017.
  28. Farhangi, A., A. Akbarzadeh, M. Mehrabi, et al. 2012. Immunotherapy of 436 morphine addicts by design to discover therapeutic monoclonal antibodies for treating methamphetamine abuse. Journal of Pharmacology and Experimental Therapeutics 322: 30–39.Google Scholar
  29. Friedman H., S. Pross, and T.W. Klein. 2006. Addictive drugs and their relationship with infectious diseases. FEMS Immunology and Medical Microbiology 47(3): 330–42.CrossRefPubMedGoogle Scholar
  30. Fox, B.S., K.M. Kantak, M.A. Edwards, et al. 1996. Efficacy of a therapeutic cocaine vaccine in rodent models. Nature Medicine 2(10): 1129–1132.CrossRefPubMedGoogle Scholar
  31. Hall, W. 2007. A research agenda for assessing the potential contribution of genomic medicine to tobacco control. Tobacco Control 16(1): 53–58.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Hall, W., and L. Carter. 2004. Ethical issues in using a cocaine vaccine to treat and prevent cocaine abuse and dependence. Journal of Medical Ethics 30(4): 337–340.CrossRefPubMedPubMedCentralGoogle Scholar
  33. Hall, W., and C. Gartner. 2011. Ethical and policy issues in using vaccines to treat and prevent cocaine and nicotine dependence. Current Opinion in Psychiatry 24(3): 191–196.CrossRefPubMedGoogle Scholar
  34. Hartmann-Boyce, J., K. Cahill, D. Hatsukami, and J. Cornuz. 2012. Nicotine vaccines for smoking cessation. Cochrane Database of Systematic Reviews 15(8): CD007072.Google Scholar
  35. Hasman, A., and S. Holm. 2004. Nicotine conjugate vaccine: Is there a right to a smoking future? Journal of Medical Ethics 30(4): 344–345.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Hubbard, J.J., E.M. Laurenzana, D.K. Williams, W.B. Gentry, and S.M. Owens. 2011. Chronic anti-phencyclidine monoclonal antibody therapy decreases phencyclidine-induced in utero fetal mortality in pregnant rats. International Immunopharmacology 11(12): 2181–2187.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Hyman, S.E. 2007. The neurobiology of addiction: Implications for voluntary control of behavior. American Journal of Bioethics 7(1): 8–11.CrossRefPubMedGoogle Scholar
  38. Jalah, R., O.B. Torres, A.V. Mayorov, et al. 2015. Efficacy, but not antibody titer or affinity, of a heroin hapten conjugate vaccine correlates with increasing hapten densities on tetanus toxoid, but not on CRM197 carriers. Bioconjugate Chemistry 26(6): 1041–1053.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Johnson, M.W., and R.H. Ettinger. 2000. Active cocaine immunization attenuates the discriminative properties of cocaine. Experimental and Clinical Psychopharmacology 8(2): 163–167.CrossRefPubMedGoogle Scholar
  40. Kaebnick, G.E. 2000. Vaccinations against bad habits. Hastings Center Report 30(5): 48.Google Scholar
  41. Kantak, K., S. Collins, E. Lipman, J. Bond, K. Giovanoni, and B.S. Fox. 2000. Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model. Psychopharmacology 148(3): 251–262.CrossRefPubMedGoogle Scholar
  42. Kantak, K.M. 2003. Vaccines against drugs of abuse. Drugs 63(4): 341–352.CrossRefPubMedGoogle Scholar
  43. Katsnelson, A. 2004. Ethical quagmire awaits vaccine for cocaine addiction. Nature Medicine 10: 1007.CrossRefPubMedGoogle Scholar
  44. Keyler, D.E., D. Soeman, M.G. LeSage, et al. 2003. Maternal vaccination against nicotine reduces nicotine distribution to fetal brain in rats. The Journal of Pharmacology and Experimental Therapy 305(2): 587–592.CrossRefGoogle Scholar
  45. Kinsey, B. 2014. Vaccines against drugs of abuse: Where are we now? Therapeutic Advances in Vaccines 2(4): 106–117.CrossRefPubMedPubMedCentralGoogle Scholar
  46. Kosten, T., M. Rosen, J. Bond, et al. 2002. Human therapeutic cocaine vaccine: Safety and immunogenicity. Vaccine 20(7): 1196–1204.CrossRefPubMedGoogle Scholar
  47. Kosten, T., and S.M. Owens. 2005. Immunotherapy for the treatment of drug abuse. Pharmacology & Therapeutics 108(1): 76–85.CrossRefGoogle Scholar
  48. Kosten, T., C. Domingo, D. Shorter, et al. 2014a. Vaccine for cocaine dependence: A randomized double-blind placebo-controlled efficacy trial. Drug and Alcohol Dependence 140: 42–47.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Kosten, T., C. Domingo, F. Orson, and B. Kinsey. 2014b. Vaccines against stimulants: Cocaine and MA. British Journal of Clinical Pharmacology 77(2): 368–374.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Landsteiner, K. 1945. The specificity of serological reactions, revised ed. New York: Dover.Google Scholar
  51. Leukefeld, C.G., and F.M. Tims. 1988. Compulsory treatment: A review of the findings. In Compulsory treatment of drug abuse: Research and clinical practice, edited by C.G. Leukefeld and F.M. Tims, 236–254. NIDA Monograph No 86. Rockville, MD: NIDA.Google Scholar
  52. Leshner, A.I. 1997. Addiction is a brain disease, and it matters. Science 278(5335): 45–47.CrossRefPubMedGoogle Scholar
  53. Li Q.Q., Y.X. Luo, C.Y. Sun, et al. 2011. A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats. Journal of Neurochemistry 119(6): 1271–1281.CrossRefPubMedGoogle Scholar
  54. Martell, B.A., E. Mitchell, J. Poling, K. Gonsai, and T.R. Kosten. 2005. Vaccine pharmacotherapy for the treatment of cocaine dependence. Biological Psychiatry 58(2): 158–164.CrossRefPubMedGoogle Scholar
  55. Martell, B., F. Orson, and J. Poling. 2009. Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Archives of General Psychiatry 66(10): 1116–1123.CrossRefPubMedPubMedCentralGoogle Scholar
  56. Maurer, P., and M.F. Bachmann. 2007. Vaccination against nicotine: An emerging therapy for tobacco dependence. Expert Opinion Investigational Drugs. 16(11): 1775–1783.Google Scholar
  57. Mets B., G. Winder, C. Cabrera, et al. 1998. A catalytic antibody against cocaine prevents cocaine’s reinforcing and toxic effects in rats. Proceedings of the National Academy of Science 95(17): 10176–10181.CrossRefGoogle Scholar
  58. Mettens P., and P. Monteyne. 2002. Life-style vaccines. British Medical Bulletin 62(1): 175–86.CrossRefPubMedGoogle Scholar
  59. Miller, M., A. Moreno, S. Aarde, et al. 2013. A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats. Biological Psychiatry 73(8): 721–728.CrossRefPubMedGoogle Scholar
  60. Miller, M.L., S.M. Aarde, A.Y. Moreno, K.M. Creehan, K.D. Janda, and M.A. Taffe. 2015. Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats. Drug and Alcohol Dependence 153: 29–36.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Moreno A.Y., A.V. Mayorov, and K.D. Janda. 2011. The impact of distinct chemical structures for the development of a methamphetamine vaccine. Journal of the American Chemical Society 133(17): 6587–6595.CrossRefPubMedPubMedCentralGoogle Scholar
  62. National Research Council. 2001. Informing America’s policy on illegal drugs: What we don’t know keeps hurting us. Washington: National Academy Press.Google Scholar
  63. Nielsen, D.A., S.C. Hamon, and T.R. Kosten. 2013. κ-opioid receptor gene as a predictor of response in a cocaine vaccine clinical trial. Psychiatric Genetics 23(6): 1–14.CrossRefGoogle Scholar
  64. Norman, A.B., and W.J. Ball Jr. 2012. Predicting the clinical efficacy and potential adverse effects of a humanized anticocaine monoclonal antibody. Immunotherapy 4(3): 335–343.CrossRefPubMedPubMedCentralGoogle Scholar
  65. Osburn, A. 2008. Immunizing against addiction: The argument for incorporating emerging anti-addiction vaccines into existing compulsory immunization statutes. Cleveland State Law Review 56: 159–188.Google Scholar
  66. Owens, S., W. Atchley, M. Hambuchen, E. Peterson, and W. Gentry. 2011. Monoclonal antibodies as pharmacokinetic antagonists for the treatment of (+)-methamphetamine addiction. CNS & Neurological Disorders - Drug Targets 10: 892–898.CrossRefGoogle Scholar
  67. Pompidou Group. 2010. Experts committee on ethical issues and professional standards. Ethical questions raised by immunotherapy of addiction. Olivier Simon. Appendix A. 16–22. Accessed 10 February, 2017
  68. Porter, L., A. Arif, and W. Curran. 1986. The law and the treatment of drug and alcohol dependent person: A comparative study of existing legislation. Geneva: World Health Organization.Google Scholar
  69. Pravetoni M.., M.D. Raleigh, M. Le Naour, et al. 2012. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats. Vaccine 30(31): 4617–4624.Google Scholar
  70. Ryan, J., C. Parker, and R. Williams. 1972. Gamma-Globulin binding of morphine in heroin addicts. Journal of Laboratory and Clinical Medicine 80(2): 155–184.PubMedGoogle Scholar
  71. Shen, X.Y., F.M. Orson, and T.R. Kosten. 2012. Vaccines against drug abuse. Clinical Pharmacology & Therapeutics 91(1): 60–70.CrossRefGoogle Scholar
  72. Shen, X., T. Kosten, A. B. Lopez, et al. 2013. A vaccine against methamphetamine attenuates its behavioral effects in mice. Drug and Alcohol Dependence 129(1): 41–48.CrossRefPubMedGoogle Scholar
  73. Spector, S and C. Parker. 1970. Morphine: Radioimmunoassay. Science 168(3937): 1347–1348.CrossRefPubMedGoogle Scholar
  74. Spooner C., W. Hall, and R.P. Mattick. 2001. An overview of diversion strategies for Australian drug-related offenders. Drug and Alcohol Review 20(3): 281–294.CrossRefGoogle Scholar
  75. Stevens, M.W., R.L. Henry, S.M. Owens, R. Schutz, and W. B. Gentry. 2014. First human study of a chimeric antimethamphetamine monoclonal antibody in healthy volunteers. mAbs 6: 1649–1656.CrossRefPubMedPubMedCentralGoogle Scholar
  76. Stowe G.N., J.E. Schlosburg, L.F. Vendruscolo, et al. 2011. Developing a vaccine against multiple psychoactive targets: A case study of heroin. CNS & Neurological Disorders - Drug Targets, 10 (B): 865–875.CrossRefGoogle Scholar
  77. Szatz, T. 1997. Ceremonial chemistry: The ritual persecution of drugs, addicts, and pushers, revised ed. Holmes Beach, FL: Learning Publications.Google Scholar
  78. Treweek, J.B., and K.D. Janda. 2012. An antidote for acute cocaine toxicity. Molecular Pharmaceutics 9(4): 969–978.CrossRefPubMedPubMedCentralGoogle Scholar
  79. Wagena E.J., A. de Vos, G. Horwith, and C.P. van Schayck. 2008. The immunogenicity and safety of a nicotine vaccine in smokers and nonsmokers: Results of a randomized, placebo-controlled phase 1/2 trial. Nicotine Tobacco Research. 10(1): 213–218.CrossRefGoogle Scholar
  80. World Medical Association 2013. Declaration of Helsinki: Ethical principles for medical research involving human subjects. 64th WMA General Assembly, Fortaleza, Brazil.Google Scholar
  81. Young M.J., D.A. Sisti, H. Rimon-Greenspan, J.L. Schwartz and A.L. Caplan. 2012. Immune to addiction: The ethical dimensions of vaccines against substance abuse. Nature Immunology 13(6): 521–524.CrossRefPubMedGoogle Scholar
  82. Volkow N.D., and T.K. Li. 2004. Drug addiction: The neurobiology of behaviour gone awry. Nature Reviews Neuroscience 5(12): 963–70.CrossRefPubMedGoogle Scholar
  83. Zalewska-Kaszubska, J. 2015. Is immunotherapy an opportunity for effective treatment of drug addiction? Vaccine 33: 6545–6551.CrossRefPubMedGoogle Scholar

Copyright information

© Journal of Bioethical Inquiry Pty Ltd. 2018

Authors and Affiliations

  1. 1.Forensic Toxicology Unit, Section of Legal MedicineUniversità degli Studi della Campania “L. Vanvitelli”NaplesItaly
  2. 2.Department of Biomedicine and PreventionUniversità degli Studi di Roma “Tor Vergata”RomeItaly

Personalised recommendations