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Not surprisingly, the high availability of cocaine in those areas where the biggest addicts live is perhaps the worst possible complication for those users who are seeking treatment. After all, says Smith, “cocaine addiction is a chronic brain disease characterized by compulsion and lack of control.”

Smith believes the best recovery programs are those that combine traditional psychosocial behavioral therapy with pharmacological treatment, because this is the best way to treat addiction in general. Many heroin addicts, for instance, are able to stay clean through a combination of counseling and daily doses of methadone, a treatment that has been available for several decades.

The Treatment

“Unfortunately,” says Janda, “there is no methadone for cocaine.”

In fact, says Janda, there currently are no suitable medications at all for treating cocaine addiction. Some compounds do exist, but these act by interfering with cocaine in the brain, leading to unwanted neurological side effects.

Janda’s new potential medication, called GND, is similar in structure to another cocaine vaccine, called GNC, which the group designed several years ago. Both vaccines are structurally similar to cocaine.

Although they have not yet undergone clinical trials, the vaccines have shown great promise in Janda’s studies. GND and GNC act by stimulating an active immune response in the bloodstream. After taking the vaccine, a patient’s immune system would, in theory, create an antibody against the vaccine, and this antibody would also target cocaine because of its similar molecular shape.

Janda also looked at boosting passive immunity by administering the antibody and not the vaccine, another way of achieving the same effect.

The studies show that the vaccine and antibody treatments given alone both suppress the psychomotor effects of cocaine for up to twelve days following vaccine inoculation. The studies also showed that the effect increased dramatically through concurrent passive immunization—administering the antibody the immune system creates at the same time as the vaccine.

In practice, the vaccine would be an integral part of certain rehabilitation processes and would be administered by health professionals in a treatment setting.

Addicts would probably receive boosters of both the vaccine and the antibody, as this combination has proven to have the longest lasting effect in the study. Then if these recovering addicts later try to get high, their immune systems will keep most of the cocaine molecules from entering the brain. The drug would then, in theory, have a minimal effect on dopamine regulation in their brains’ pleasure centers.

They wouldn’t feel high, and they wouldn’t experience psychological reinforcement. Hopefully, this would help prevent relapse, the bane of all treatment programs.

“You have to prevent relapse early,” says Smith. “The vaccine will be good for keeping people on the path of recovery.”

An Uncertain Future

Though the GNC and GND molecules are very similar—both structurally and in terms of how they stimulate the immune system—the antibodies they produce are not the same.

In the laboratory, model systems using GND, the new vaccine, showed a slightly greater efficacy than previous models that used GNC. However, this greater laboratory efficacy may not mean that the newer compound will replace the older one before either eventually finds use in treatment. Both are years away, and GND is in a much earlier stage of development than GNC.

GNC, the original vaccine, has already gone through a lengthy testing process and is coming close to human trials. The vaccine had to be made non-toxic to humans. Plus details of its synthesis had to be worked out so that it can be manufactured easily and on a massive scale.

These issues necessitated an investment of basic science capital long before GNC was even close to reaching patients. Janda’s work has been funded through NIDA, with a big boost coming from the generous private contributions of the Joseph Drown Foundation and Mr. Robert E. Martini.

Such support allowed Janda to extend his work on GNC and make the second-generation vaccine, GND. Whether or not GND makes it to the clinic or even as far as human trials, though, depends a lot on whether there is any interest in developing the compound clinically.

“It works like gangbusters,” says Janda, “But it’s not as synthetically accessible as the original.”

Not yet.


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Structures of cocaine and the vaccines GNC (middle), and GND (bottom). In GND the C-2 and C-3 esters in GNC have been exchanged for amides, which improves hydrogen bonding with the antibody.












See also:

The Janda Laboratory

Article: M. Rocio A. Carrera, Jon A. Ashley, Peter Wirsching, George F. Koob, and Kim D. Janda, "A second-generation vaccine protects against the psychoactive effects of cocaine," Proceedings of the National Academy of Sciences, USA, Vol. 98, Issue 4 (Feb. 13, 2001), 1988-1992.