Vaccine to treat cocaine addiction yields promising results

A vaccine for treating cocaine addiction has produced promising results in trials in non-human primates. Cocaine is a potent psychostimulant that evokes feelings of euphoria and increased wakefulness by increasing activity of the neurotransmitter, dopamine, in certain brain regions. Dopamine signalling is usually terminated by recycling of the neurotransmitter back into neurons, facilitated by the dopamine reuptake transporter (DAT). Cocaine blocks this carrier, increasing the duration of dopamine activity in the synapse.

The group, led by Dr Ronald Crystal, have developed a vaccine consisting of a cocaine analogue linked to highly immunogenic proteins derived from a human adenovirus. Immunisation triggers an immune reaction that results in production of antibodies against the complex, some of which recognise the cocaine moiety. If a vaccinated individual then uses cocaine, the antibodies in the blood bind the drug and prevent it from entering the brain via the blood brain barrier. This effectively blocks the high-inducing action of cocaine on the CNS, removing the positive reinforcement that contributes to maintaining addiction.

Having already shown that the vaccine inhibits the behavioural effects of cocaine in rodents, the group used PET (positron emission tomography) to analyse binding of a radiolabelled tracer molecule to DAT. In the absence of cocaine, there was no difference in binding of the radiotracer to DAT between vaccinated and non-vaccinated subjects. When cocaine was administered, however, tracer binding dropped significantly as it was displaced by cocaine, while the displacement was much less in the vaccinated subjects. This indicates that the vaccine successfully prevented cocaine from reaching and acting on the dopamine synapse.

Whereas most pharmacological approaches to treating drug addiction have unwanted side effects because they interfere with brain signalling pathways, this immune-based approach is less likely to produce side effects. Other vaccines based on modified adenoviruses have proved safe in this and several other trials.

This research appears as an advance online preview published in Neuropsychopharmacology: http://www.ncbi.nlm.nih.gov/pubmed/23660705