Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial

Arch Gen Psychiatry. 2009 Oct;66(10):1116-23. doi: 10.1001/archgenpsychiatry.2009.128.


Context: Cocaine dependence, which affects 2.5 million Americans annually, has no US Food and Drug Administration-approved pharmacotherapy.

Objectives: To evaluate the immunogenicity, safety, and efficacy of a novel cocaine vaccine to treat cocaine dependence.

Design: A 24-week, phase 2b, randomized, double-blind, placebo-controlled trial with efficacy assessed during weeks 8 to 20 and follow-up to week 24.

Setting: Cocaine- and opioid-dependent persons recruited from October 2003 to April 2005 from greater New Haven, Connecticut.

Participants: One hundred fifteen methadone-maintained subjects (67% male, 87% white, aged 18-46 years) were randomized to vaccine or placebo, and 94 subjects (82%) completed the trial. Most smoked crack cocaine along with using marijuana (18%), alcohol (10%), and nonprescription opioids (44%).

Intervention: Over 12 weeks, 109 of 115 subjects received 5 vaccinations of placebo or succinylnorcocaine linked to recombinant cholera toxin B-subunit protein. Main Outcome Measure Semiquantitative urinary cocaine metabolite levels measured thrice weekly with a positive cutoff of 300 ng/mL.

Results: The 21 vaccinated subjects (38%) who attained serum IgG anticocaine antibody levels of 43 microg/mL or higher (ie, high IgG level) had significantly more cocaine-free urine samples than those with levels less than 43 microg/mL (ie, low IgG level) and the placebo-receiving subjects during weeks 9 to 16 (45% vs 35% cocaine-free urine samples, respectively). The proportion of subjects having a 50% reduction in cocaine use was significantly greater in the subjects with a high IgG level than in subjects with a low IgG level (53% of subjects vs 23% of subjects, respectively) (P = .048). The most common adverse effects were injection site induration and tenderness. There were no treatment-related serious adverse events, withdrawals, or deaths.

Conclusions: Attaining high (>or=43 microg/mL) IgG anticocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated subjects attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters. Trial Registration Identifier: NCT00142857.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Cocaine-Related Disorders / blood
  • Cocaine-Related Disorders / rehabilitation
  • Cocaine-Related Disorders / therapy*
  • Double-Blind Method
  • Enzyme-Linked Immunosorbent Assay / statistics & numerical data
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / blood
  • Immunotherapy, Active / methods*
  • Male
  • Methadone / therapeutic use*
  • Middle Aged
  • Opioid-Related Disorders / rehabilitation
  • Opioid-Related Disorders / therapy
  • Substance Abuse Detection
  • Treatment Outcome


  • Immunoglobulin G
  • Methadone

Associated data