Evidence-Based Reviews

Vaccine for cocaine addiction: A promising new immunotherapy

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

Blocking cocaine from reaching the brain may help curb use

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.

6. Kosten TR, Rosen M, Bond J, et al. Human therapeutic cocaine vaccine: safety and immunogenicity. Vaccine. 2002;20:1196-1204.

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

8. Pani PP, Trogu E, Vacca R, et al. Disulfiram for the treatment of cocaine dependence. Cochrane Database Syst Rev. 2010;(1):CD007024.-

9. Dackis CA, Kampman KM, Lynch KG, et al. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. Neuropsychopharmacology. 2005;30(1):205-211.

10. Anderson AL, Reid MS, Li SH, et al. Modafinil for the treatment of cocaine dependence. Drug Alcohol Depend. 2009;104(1-2):133-139.

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.

13. Johnson BA, Roache JD, Ait-Daoud N, et al. A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence. Drug Alcohol Depend. 2006;84(3):256-263.

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.

The cocaine vaccine: How will it be used? Drs. Anthenelli and Somoza discuss adherence to the TA-CD vaccine, and more

Discuss this article at http://currentpsychiatry.blogspot.com/2010/09/vaccine-for-cocaine-addiction.html#comments

Unlike opioid or alcohol abuse, for cocaine dependence there are no FDA-approved pharmacotherapies, which leaves psychosocial treatment as the standard of care for the estimated 1.6 million individuals in the United States who abuse cocaine.¹ However, researchers are developing a novel way to help cocaine-dependent patients reduce their drug use. Therapy for addiction–cocaine addiction (TA-CD) is thought to curb cocaine use by engaging the body’s immune reaction and stopping cocaine molecules from reaching the brain, thereby reducing the drug’s pleasurable effects. One researcher working on this vaccine, Eugene Somoza, MD, PhD—the principal investigator of the Ohio Valley Node of the National Institute on Drug Abuse clinical trials network of 16 universities and treatment programs—discusses with Current Psychiatry Section Editor Robert M. Anthenelli, MD, how TA-CD works and how it might be used in clinical practice.

DR. ANTHENELLI: How is immunotherapy being applied to treating cocaine addiction and how does TA-CD work?

Clinical Point

When antibodies bind to cocaine in the blood stream, the molecule becomes too large to cross the blood-brain barrier

DR. SOMOZA: Our bodies have a very efficient immune system that can recognize foreign proteins and other complex molecules and develop specific antibodies against them that join irreversibly to these molecules to make them inactive. Immunotherapy usually is used to treat disorders that involve very complex molecules. Cocaine is a very simple molecule, but you can attach a simple molecule to a complex molecule and still trigger the immune system. You can use this method to develop antibodies to cocaine. When an individual uses cocaine, the antibodies will bind to the cocaine in the blood stream and the drug never reaches the brain because the molecule is now too large to pass the blood-brain barrier. The reinforcing properties of addictive agents depend on how fast they get into the brain. By slowing down or even stopping this process, you decrease the pleasurable effect individuals get from cocaine.

The cocaine vaccine that is being tested makes use of the B subunit of the cholera toxin molecule. It is highly immunogenic, and a recombinant of it is available in large quantities.² Cocaine molecules are connected to various areas of this complex cholera toxin subunit with covalent bonding. This makes the cocaine a larger target for an antibody response.

The interesting aspect of this process is that the vaccine acts outside of the brain. Other pharmacotherapies being tested, such as modafinil and disulfiram, target receptors or enzymes within the brain, which means that these 2 types of treatment would be synergistic. An early article on cocaine vaccines by Fox et al³ emphasized that this therapy is compatible with other treatments.

DR. ANTHENELLI: After receiving the vaccine, how long does it take for antibody levels to be high enough to produce a therapeutic effect?

DR. SOMOZA: Typically about 8 weeks.

DR. ANTHENELLI: Some trials have shown that patients display high variability in antibody levels. Only 38% of subjects in a 24-week, randomized, double-blind, placebo-controlled trial by Martell et al⁴ achieved high antibody levels (≥43 μ/mL). Are there ways to predict who will achieve the higher antibody titers and to increase the percentage of people who might develop the antibodies?

Clinical Point

We estimate that 40% of patients receiving the vaccine will develop ≥40 μ/mL of antibodies; this level is necessary for heavy users

DR. SOMOZA: Right now there are not. In the Martell study, subjects’ antibody response curves—the increase and subsequent decrease in antibody concentration—were very different from individual to individual. We estimate that 40% of patients receiving the vaccine will develop ≥40 μ/mL of antibodies; this level is necessary for heavy cocaine users. However, not all patients take large amounts of cocaine, so we expect that even if a patient develops 30 μ/mL of antibodies, the amount of cocaine reaching the brain will be reduced— although the process may be slower—and using will not be as enticing.⁵

DR. ANTHENELLI: How long will the effects of TA-CD last, and how often will patients need to receive booster shots to keep antibody titers high?

DR. SOMOZA: The antibodies stay high for approximately 10 to 30 weeks, so you have to give boosters periodically. We need to carefully study if one can give a patient a booster every few months and, if so, how many booster shots would be required.

DR. ANTHENELLI: What are the known side effects of the vaccine?