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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

contribute to the very high rate of relapse in individuals that can take place
after years of abstinence.

Pharmacological treatment of cocaine dependence
Various approaches are being examined in the treatment of cocaine
dependence. Because cocaine has potent effects on the dopamine
transporter, medications that bind to the dopamine transporter have been
tested. GBR 12909 is a selective and potent inhibitor of dopamine uptake
that antagonizes the effects of cocaine on mesolimbic dopamine neurons in
rats (Baumann et al., 1994), and blocks self-administration of cocaine
in rhesus monkeys (Rothman & Glowa, 1995). Clinical trials of this drug are
in the planning stage.
A novel strategy for treating cocaine dependence is the development of
anti-cocaine antibodies, or immunotherapies to prevent cocaine from
entering the brain. This approach differs significantly from traditional types
of pharmacotherapies in that after cocaine is consumed, it is sequestered in
the bloodstream by cocaine-specific antibodies that prevent its entry into
the brain. One benefit from using a peripheral cocaine-blocking agent is that
side effects typically associated with penetration of therapeutic drugs into
the central nervous system are avoided.
The cocaine vaccine IPC-1010 has been tested in preclinical studies that
were initiated by ImmuLogic Pharmaceutical Corporation in collaboration
with Boston University and then continued under the name TA-CD in clinical
studies conducted by Cantab Pharmaceuticals plc and Xenova Group plc in
collaboration with Yale University, and support from The National Institute
on Drug Abuse.
A series of studies assessed the preclinical effectiveness of anti-cocaine
antibodies and the cocaine vaccine IPC-1010 on cocaine self-administration
behaviour in rats. Active immunization with IPC-1010 significantly reduced
both drug-seeking behaviour and the number of drug infusions earned
compared to pre-immunization levels. Only rats having serum antibody levels
greater than 0.05 mg/ml displayed attenuated drug-seeking behaviour and
number of drug infusions across the range of doses examined. Active
immunization with IPC-1010 with access to cocaine during immunization
suggested that daily exposure to cocaine during the immunization period
does not interfere with the ability of the immunotherapy to induce antibody
formation and reduce cocaine self-administration behaviour. Studies also
showed that immunization with IPC-1010 specifically decreased cocaine-
seeking, and did not affect responding for another reward of food pellets.
In a phase I study, the safety and immunogenicity of TA-CD were evaluated
in three groups of abstinent cocaine abusers (Kosten et al., 2002).
Immunization with TA-CD induced cocaine-specific antibodies in the three
groups of human subjects. The first clearly detectable anti-cocaine antibodies
appeared on day 28 (14 days after the second immunization) which

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