Scientists at The Scripps Research Institute (TSRI) have been working to develop vaccines for drug addiction since the early 1990s. Currently, TSRI vaccines for cocaine and nicotine addiction are in clinical trials, with one for methamphetamine nearing the research phase. However, heroin addiction has proven especially hard to treat through a vaccine because the body rapidly metabolizes it into several other compounds, making it more difficult to target the drug molecules.
A TSRI research team led by Professor Kim Janda and Professor George F. Koob, who chairs TSRI's Committee on the Neurobiology of Addictive Disorders, has developed a vaccine that successfully prevents heroin from reaching the brain. In trials, the vaccine caused heroin-addicted rats with access to an unlimited supply of the drug to stop taking it.
"Heroin-addicted rats deprived of the drug will normally resume using it compulsively if they regain access, but our vaccine stops this from happening," said Dr. Koob. If the vaccine proves as effective in human trials, it could help heroin addicts committed to recovery; heroin addiction is estimated to affect more than 10 million people worldwide. Because heroin is often injected, users who share syringes are not only at risk for fatalities from overdose, but also of contracting many other diseases including HIV and hepatitis C.
Professor Kim Janda
The TSRI vaccines treat drug addiction by causing the immune system to treat the drug molecules as a pathogen, like a bacteria or virus, and to send out antibodies to bind to them and neutralize them before they enter the brain – where they cause the high that addicts crave. Common drug molecules are too small and simple to stimulate the immune system sufficiently on their own, but vaccine designers affix key fragments of the molecules to larger more immune-provoking carrier proteins.
Designing an effective vaccine against heroin has been particularly challenging because the drug breaks down rapidly in the bloodstream into 6-acetylmorphine and morphine. The TSRI team had to develop a vaccine that not only triggered antibodies for heroin, but these other molecules as well.
"The vaccine effectively tracks the drug as it is metabolized, keeping the active breakdown products out of the brain, and that, I think, explains its success," said Dr. Janda, who is TSRI's Ely R. Callaway, Jr. Chair in Chemistry, and whose laboratory initially developed the vaccine three years ago.
After Dr. Janda's initial success, researchers in Dr. Koob's laboratory put the vaccine through more rigorous tests. In one test, severely addicted rats taking heroin compulsively in escalating amounts were forced to abstain from the drug for 30 days before their access was renewed. In rats that had received a dummy vaccine, compulsive heroine intake resumed and re-escalated. But in the vaccinated rats, intake failed to escalate and none of the rats resumed compulsively taking the drug.
"Basically we were able to stop them from going through that cycle of taking more and more heroin," said TSRI Research Associate Joel Schlosburg. "And that was with the vaccine alone; ideally for human patients, the vaccine would be given with other treatments."
Users frequently relapse after conventional treatment for heroin addiction, and the vaccine may prevent renewed addiction in people who begin taking the drug again after beginning recovery. The vaccine would also likely make it impossible for an addict to overdose on the drug since the drug is neutralized before it can do any damage. The vaccine could be ready for human trials later this year.