Stimulant Addiction

There are no FDA-approved treatments for cocaine and methamphetamine dependence at the present time. However, there are a number of promising medications that are under clinical investigation presently (Table 5). As reviewed elsewhere, these include but are not limited to disulfiram, and the GABA uptake inhibitor tiagabine, as well as topirimate, modafinil, baclofen,62 and anti-cocaine vaccines.63

The anti-cocaine vaccine induces the production of anti-cocaine antibodies, which are hypothesized to bind peripherally circulating cocaine, preventing it from penetrating the blood-brain barrier. Thus this immunogenic response serves as a 'sponge' mechanism to prevent cocaine from getting into the brain.64 Cocaine itself cannot induce this immune response, but when it is covalently linked to a carrier protein, it can become a haptenic molecule with immunogenic properties. The carrier protein both stimulates T cell-mediated antibody production but also provides a scaffold upon which cocaine is able to cross-link immunoglobulin on the surface of B cells.64 Cocaine, or a cocaine derivative, is linked to a carrier protein such as keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA). One such conjugate has been shown to achieve levels of anti-cocaine antibody that suppressed cocaine-induced locomotor activity and stereotypical behaviors.64 By replacing the 2-position ester with an amide linkage, the resulting vaccine could suppress cocaine-induced locomotor activity for up to 12 days, which was a dramatic improvement and suggested long-term protection against CNS effects of cocaine. Currently, safety and efficacy studies are being conducted in humans to assess medication potential in humans.

The development of medications to treat stimulant addiction remains a challenging area. It is likely that no single agent will provide an entirely satisfactory treatment, but that combining agents that work via different mechanisms to optimize therapeutic response will be the pathway that cocaine therapeutic development follows. Section describes current preclinical targets with candidates that appear to show promise for treating cocaine abuse in animal models.

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