Heroin vaccine blocks drug addiction in rats

style="float: right; margin-bottom: 10px; font-weight: 600;"Tue 4th Jun, 2013

A team of scientists from The Scripps Research Institute in California, USA, has reported promising results for a new vaccine against heroin. The vaccine can target not only heroin directly, but also its specific breakdown products in the blood, effectively stopping them from reaching the brain, at least in rats.

"Vaccines against drugs of abuse, including heroin, have been tested and developed since the early 1970s, however most attempts failed due to either targeting morphine or targeting heroin and all their metabolites in a very non-specific way", said Dr Joel Schlosburg, first author in the study and postdoctoral research associate in the labs of Dr George Koob and Dr Kim Janda, who have started this work a few years ago.

Developing this vaccine was particularly complicated, as heroin breaks down very quickly in the bloodstream after injection, originating morphine and a compound called 6-acetylmorphine. These smaller compounds have the ability to cross into the brain and explain much of this drug's effects. The team decided to embrace this fast metabolic mechanism in the body and developed a vaccine that would be metabolised in a similar way to heroin. This vaccine triggered an immune reaction against each of the compounds resulting from heroin injection and roughly in the same proportion to how quickly they were being produced.

"The heroin vaccine makes surprisingly few heroin antibodies, but heroin only lasts seconds in the bloodstream. The key to our effectiveness appears to be the high affinity binding generated against heroin's primary metabolite (6-acetylmorphine) which is around for roughly 20-40 min following injection", explained Dr Schlosburg.

As heroin was too small to generate a reaction from the immune system by itself, the vaccine designers attached the drug to a known 'helper' protein that can cause a robust immune reaction. In response, the body produces antibodies - proteins that tag foreign molecules for destruction - not only against the 'helper' protein, but also against heroin. As the authors reported in a previous study, the trick of this 'dynamic' vaccine is to attach the protein to the non-reactive part of heroin, leaving the reactive part free to be recognised by the metabolic machinery in the body and by the immune system. As a result, antibodies are produced against heroin, 6-acetylmorphine, and morphine.

During the study, rats were trained to receive heroin by pushing a lever, followed by a 'cold turkey' period without the drug. When the drug became available again, vaccinated rats didn't show any interest in resuming their drug-taking habit, whereas a single use of heroin was enough to reinstate addiction in non-vaccinated animals. Even when the rats received increasingly higher doses of heroin, compulsive intake never re-emerged in vaccinated animals after a period of abstinence.

Crucially, the vaccine stopped the vicious cycle of taking more and more heroin and prevented relapses. Dr Schlosburg believes the animals eventually figured out that there was no point in taking heroin, as they experienced no feeling of craving or reward.

In theory, after immunisation, "when heroin users go to inject themselves again, the antibodies are ready to bind heroin and all its metabolites as soon as they enter the bloodstream. This way, nothing slips through via metabolism, and all gets bound up. Since antibodies can't cross into the brain from the periphery, the heroin gets trapped outside the brain and is eventually flushed out of the system without producing any of its psychoactive effects", explained Dr Schlosburg.

At this stage, "we are trying to find benefactors and pharmaceutical partners to potentially get initial clinical trials running as soon as reasonably possible", continued Dr Schlosburg. "We're confident that trials for efficacy against heroin users will be a matter of years, not decades away". If the vaccine works as well as expected, it has the potential to become standard therapy for heroin addicts, estimated to be nearly 20 million people worldwide. "This vaccine can probably completely replace the use of long-term antagonist therapies, since it does the same thing, but with less need for patient compliance, less monitoring and side-effects, and allowing for treatment with other opioid-based therapies".

Dr Carl Alving, immunologist and research investigator from the U.S. Military HIV Research Program has a word of caution. Although the study "shows convincingly that this vaccine blocks many of the important psychoactive effects of heroin in rats, the creation of a practical vaccine formulation would require further work", including an alternative heroin carrier more suitable for use in humans, a new adjuvant and ensure stability during storage. Despite the warning, Dr Alving concluded that "if all these items are solved, this vaccine might serve as a candidate for further testing as a potential heroin vaccine."

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