Introduction: The United Nations Office on Drugs and Crime (UNODC) estimates the annual prevalence of cocaine use between 0.3 – 0.4 %, affecting 13 – 20 million individuals between 15 and 64 years of age. Small molecule approaches have only been marginally successful in developing therapies for substance use disorders (SUDs). There are no approved medications to treat cocaine addiction. Biological approaches are all grounded on a common mechanism: either exclude or retard the entry of cocaine from the central nervous system. Methods: Published literature and conference lectures about biological therapies of cocaine addiction. Results: There are currently three means of achieving this objective: 1. vaccines that stimulate the immune system to produce antibodies directed against cocaine specific; 2. passive immunization by administering monoclonal antibodies directed against cocaine; 3. genetically engineered esterases that catalyze the hydrolysis of cocaine in a much greater way than the wild-type enzyme. Administration of mutated butyrylcholinesterase linked to serum albumin dramatically reduces both the toxicological and behavioral effects of cocaine in nonhuman primates. These effects are attributable to a rapid degradation of cocaine in plasma and subsequent greater hydrolysis of ecgonine methylester. Discussion: Immunotherapies may help to prevent relapse in addicted patients who are motivated to remain abstinent, however they are less likely to be successful for inducing abstinence in heavily cocaine addicted individuals. To enhance chances for effectiveness, they should be combined with other behavioral and pharmacological therapies. Conclusion: Hopefully, those challenges will be resolved and biologics for SUDs will be approved by the FDA or related authorities, to become part of the therapeutic armamentarium to curtail this serious disorder.

Key words: cocaine addiction – biologics – biologics to treat addiction – vaccines – monoclonal antibodies – butyrylcholinesterase – cocaine esterase – cocaine hydrolase – cocaethylene