Background:Anti-drug antibodies reduce drug levels in the brain by binding drug before it enters the brain. Because antibodies are much larger than drugs,neither the antibody nor bound drug can get into the brain. Thus,any drug that is bound to antibody cannot cross the blood brain barrier and cannot enter the brain. Active anti-drug vaccines stimulate the body to make its own antibodies by chemically linking these abused drugs to toxins such as cholera toxin. The cocaine vaccine has been tested in humans with excellent success and those clinical trials will be presented. Antibodies can treat drug overdose; reduce drug use relapse; or protect certain at risk populations who have not yet become drug dependent. Objective:This presentation will present phase 2 studies of a human cocaine vaccine (TA-CD) and animal studies of new cocaine and other vaccines with improved immunogenicity as an alternative pharmacotherapy for cocaine and other drug addiction. Methods:(1)Human laboratory cocaine administration studies; (2)Randomized placebo controlled,clinical trials; (3)Rodent studies of new vaccine carriers with antibody levels presented. Results:New innovations in technology have facilitated the development of drug-protein conjugate vaccines,which elicit antibodies of high affinity that are specifically capable of neutralizing the drug in the body and attenuating its pharmacological effects. (1)TA-CD vaccine in humans produces dose-dependent blockade of up to 50 mg of smoked cocaine. (2)A randomized placebo controlled,clinical trial of TA-CD in outpatient cocaine addicts showed significant reductions in cocaine use among those 40% of vaccinated subjects who attained antibody levels above 43 ug·ml-1,which is the calculated antibody level needed to block 0.5 mg·ml-1 of intravenous cocaine. (3)A new vaccine carrier from Merck has increased peak antibody levels three fold and raised antibodies to these levels in half the time required with TA-CD in rodents. We also have similar vaccines for morphine and methamphetamine. Conclusion:Recent advances in biotechnology make vaccines feasible as potential pharmacotherapies for drug addiction. Unlike small molecules targeting the neural pathways and receptors involved in drug addiction,these protein therapies target the drug itself,providing alternative strategies for medications development. A cocaine vaccine has shown preliminary success by acting as a buffer to slow the pharmacokinetics of drug entry into the brain and thereby markedly reducing euphoria. Similar vaccines for morphine and methamphetamine are in animal studies. Background: Anti-drug antibodies reduce it in the brain by binding drug before it enters the brain. Thus, any drug that is bound to the brain can not cross the blood brain barrier and can not enter the brain. Active anti-drug vaccines stimulate the body to make its own antibodies by chemically linking these abused drugs to toxins such as cholera toxin. The cocaine vaccine has been tested in humans with excellent success and Those clinical trials will be presented. Antibodies can treat drug overdose; reduce drug use relapse; or protect certain at risk populations who have not yet become drug dependent. Objective: This presentation will present phase 2 studies of a human cocaine vaccine (TA-CD ) and animal studies of new cocaine and other vaccines with improved immunogenicity as an alternative pharmacotherapy for cocaine and other drug addiction. Methods: (1) Human laboratory cocaine (3) Rodent studies of new vaccine carriers with antibody levels presented. Results: New innovations in technology have facilitated the development of drug-protein conjugate vaccines, which elicit antibodies of high affinity that are specifically capable of neutralizing the drug in the body and attenuating its pharmacological effects. (1) TA-CD vaccine in humans produces dose-dependent blockade of up to 50 mg of smoked cocaine. (2) A randomized placebo controlled, clinical trial of TA-CD in outpatient cocaine addicts showed significant reductions in cocaine use among those 40% of vaccinated subjects who attained antibody levels above 43 ug · ml-1, which is the calculated antibody level needed to block 0.5 mg · ml- 1 of intravenous cocaine. (3) A new vaccine carrier from Merck has increased peak antibody levels three fold and raised antibodies to these levels in half the time required with TA-CD in rodents. We also have simi laConclusion: Recent advances in biotechnology make vaccines feasible as potential pharmacotherapies for drug addiction. Unlike small molecules targeting the neural pathways and receptors involved in drug addiction, these protein therapies target the drug itself, providing alternative strategies for medications development. A cocaine vaccine has shown preliminary success by acting as a buffer to slow the pharmacokinetics of drug entry into the brain and thereby markedly reduced euphoria. Similar vaccines for morphine and methamphetamine are in animal studies.