Evidence-Based Reviews

Vaccine for cocaine addiction: A promising new immunotherapy

Current Psychiatry. 2010 September;9(9):16-A

References

1. Substance Abuse and Mental Health Services Administration. 2007 national survey on drug use and health. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2008.

2. Jertborn M, Svennerholm AM, Holmgren J. Safety and immunogenicity of an oral recombinant cholera B subunit-whole cell vaccine in Swedish volunteers. Vaccine. 1992;10:130-132.

3. Fox BS, Kantak KM, Edwards MA, et al. Efficacy of a therapeutic cocaine vaccine in rodent models. Nat Med. 1996;2:1129-1132.

4. Martell BA, Orson FM, Poling J, et al. Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Arch Gen Psychiatry. 2009;66(10):1116-1123.

5. Haney M, Gunderson EW, Jiang H, et al. Cocaine-specific antibodies blunt the subjective effects of smoked cocaine in humans. Biol Psychiatry. 2010;67(1):59-65.

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7. Grabenstein JD. ImmunoFacts: vaccines and immunological drugs. St. Louis, MO: Facts and Comparisons, Inc.; 1994:487b.

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11. Winhusen T, Somoza E, Ciraulo DA, et al. A double-blind, placebo-controlled trial of tiagabine for the treatment of cocaine dependence. Drug Alcohol Depend. 2007;91 (2-3):141-148.

12. Kahn R, Biswas K, Childress AR, et al. Multi-center trial of baclofen for abstinence initiation in severe cocaine-dependent individuals. Drug Alcohol Depend. 2009;103 (1-2):59-64.

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14. Norman AB, Tabet MR, Norman MK, et al. A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice. J Pharmacol Exp Ther. 2007;320:145-153.

15. Norman AB, Norman MK, Buesing WR, et al. The effect of a chimeric human/murine anti-cocaine monoclonal antibody on cocaine self-administration in rats. J Pharmacol Exp Ther. 2009;328:873-881.

16. Cornuz J, Zwahlen S, Jungi WF, et al. A vaccine against nicotine for smoking cessation: a randomized controlled trial. PLoS One. 2008;3(6):e2547.-

17. Wagena EJ, de Vos A, Horwith G, et al. The immunogenicity and safety of a nicotine vaccine in smokers and nonsmokers: results of a randomized, placebo-controlled phase 1/2 trial. Nicotine Tob Res. 2008;10(1):213-218.

18. Hatsukami DK, Rennard S, Jorenby D, et al. Safety and immunogenicity of a nicotine conjugate vaccine in current smokers. Clin Pharmacol Ther. 2005;78(5):456-467.

19. Maurer P, Bachmann MF. Vaccination against nicotine: an emerging therapy for tobacco dependence. Expert Opin Investig Drugs. 2007;16(11):1775-1783.

20. Volkow ND. Message from the director on ARRA funding for the development of a nicotine vaccine. National Institute on Drug Abuse Web site. Available at: http://drugabuse.gov/about/welcome/nicotinevaccine909.html. Accessed August 13, 2010.

21. Laurenzana EM, Hendrickson HP, Carpenter D, et al. Functional and biological determinants affecting the duration of action and efficacy of anti-(+)-methamphetamine monoclonal antibodies in rats. Vaccine. 2009;27(50):7011-7020.

Related Resource

Martell BA, Mitchell E, Poling J, et al. Vaccine pharmacotherapy for the treatment of cocaine dependence. Biol Psychiatry. 2005;58(2):158-164.

Drug Brand Names

Baclofen • Lioresal
Digoxin • Lanoxin
Digoxin immune fab • Digibind
Disulfiram • Antabuse
Modafinil • Provigil
Ondansetron • Zofran
Tiagabine • Gabitril

Disclosure

Dr. Anthenelli receives grant/research support from Eli Lilly and Company, Nabi Biopharmaceuticals, and Pfizer Inc., and is a consultant to Pfizer Inc.

Dr. Somoza receives grant/research support from the National Institute on Drug Abuse.

Drs. Norman and Ball receive grant/research support from the National Institutes of Health and the National Institute on Drug Abuse and are consultants to Vybion, Inc.

Box 3

Additional commentary from Drs. Anthenelli and Somoza

Treatment adherence

DR. ANTHENELLI: We know from working in the addiction field that compliance with medication regimens is a big challenge. What are the data regarding adherence to TA-CD?

DR. SOMOZA: We don’t have any specific data about adherence to the vaccine, but it is probably similar to any other medication for addiction. Remember that cocaine-dependent patients often are erratic and don’t use planners to set up their day. If you look at clinical trials over the past 20 years, if you get 75% retention you’re doing really good, but quite often you see 50% or 25% retention. With TA-CD, retention is going to be worse because you have to wait 8 weeks before patients build up enough antibodies to have therapeutic effect. I’m hoping we can convince the FDA to look at the relationship between antibody generation and improvement in treatment efficacy. Obviously if patients don’t develop antibodies they’re not going to get better.

Patient characteristics

DR. ANTHENELLI: I know it’s a little early, but if you had to use your crystal ball, what type of patient do you think that TA-CD might work best for?

DR. SOMOZA: Certainly it would be for people that are motivated to stop using. If they really don’t want to stop using cocaine, probably nothing will work. These patients could get the vaccine and boosters and it won’t do them any good. They’ll take it and nothing happens.

Future research

DR. ANTHENELLI: One of the things you have discussed is who will achieve enough antibody titers to make TA-CD effective. Are there other kinds of research you think will be related to this?

DR. SOMOZA: Increasing the serum concentration of the antibodies is one. Another would be to increase the fraction of people who develop high levels of antibodies. One wonders if we could use a different protein that would increase the immunogenicity of the vaccine. If we use 2 different proteins, perhaps the effects would be additive. In an early study of mice, Fox and colleagues^a used a blood protein, not a cholera toxin.

References

a. Fox BS, Kantak KM, Edwards MA, et al. Efficacy of a therapeutic cocaine vaccine in rodent models. Nat Med. 1996;2:1129-1132.