In the near future, your doctor may be able to offer you a shot to guard against heroin as easily as she can give you one for tetanus or diphtheria. Anti-drug vaccines could soon be a viable option for users who want to kick their habits—and they’re shifting how we think about addiction.
Currently, there are injectable treatments in development for all of the so-called “Big Four” addictive substances: methamphetamine, nicotine, heroin, and cocaine addictions. While individual vaccines vary, they all tend to work by training the immune system to produce antibodies as soon as the user’s drug of choice enters the body. In the untreated user, the tiny drug molecules would pass into the brain undetected and change the normal chemical transmissions between nerve cells, causing “highs” and other effects. In the vaccinated user, the immune system instead identifies the offending particles and binds them with large antibodies that keep them from interfering with receptors. With enough antibodies on duty, all the incoming drug molecules are changed before they can cause any damage, eliminating the psychedelic effects and euphoria.
And just as the high never hits, it would be difficult (and expensive) to consume enough of the drug to overwhelm the body’s immune system and cause an overdose. Many overdoses are caused by respiratory failure brought on when the drugs interfere with normal brain chemistry…but for the vaccinated user, the drugs never reach the brain.
Does it work? Scientists have given lethal doses of heroin to vaccinated rats and watched them run around “happy as clams,” according to Kim Janda, one of the top addiction vaccine researchers and director of the Worm Institute for Research and Medicine at The Scripps Research Institute. Vaccines in development for heroin and cocaine look promising: in 2013, researchers showed a vaccine could block heroin relapses in mice and bind cocaine outside the brain in primates. There is also a big market for a nicotine vaccine for the millions of smokers who try to quit every year, though clinical trials in humans have so far been unsuccessful.
“I don’t know if every drug is going to be tractable,” Janda said, “but I do believe that out of the Big Four, in my lifetime, we’ll get one of these things approved.”
Many anti-drug vaccines in development rely on linking the drug molecules to larger proteins so that the immune system recognizes them. The vaccine then works like any other shot: the body recognizes a pathogen, calls out the troops, and defeats the infection. Some of the cells created are particularly long-lived and retain a memoryof the offender—the drug molecule sitting on the protein—allowing the immune system to recognize it and respond quickly if it enters the body again.
Existing treatments have focused on the workings of the brain itself, rather than the bloodstream, where vaccine antibodies work. Methadone, for example, mimics opioid drugs in the brain, relieving cravings while blocking the euphoric effects from drug use to discourage the habit. Vivitrol, another treatment for opioids, and Chantix, which targets nicotine, are similar blockers that attach directly to neural receptors. It’s hoped that anti-drug shots will prove particularly valuable when used in tandem with other types of treatments and counseling, attacking a historically intractable problem from multiple angles.
“We don’t view [vaccines] as a standalone,” Janda says. “This isn’t the magic bullet.”
Interestingly, while an anti-cocaine or anti-heroin vaccine eliminates the drugs effects (both pleasant and unpleasant), that doesn’t by itself curb a user’s desire. The person still has to want to get clean, in other words, and Janda cautions the vaccines’ potential is not as a cure-all, but rather as a powerful aid to help remove the temptation (why do the drug if it doesn’t work?) and as a net to catch someone during their weak moments.
Another limitation with vaccines is the booster shots required to keep the antibody memory alive. To lengthen the time between shots or potentially eliminate them altogether, researchers at Weill Cornell Medical College developed a different kind of vaccine that uses a virus to inject the biological code for a cocaine antibody into liver cells. In their promising experiment, the mice pumped out the antibody continuously along with other molecules made fresh daily.
While there has been great progress in anti-drug vaccines over the past 25 years, there are still many hurdles to overcome. Each addictive drug has its own unique shape, pathways, derivatives, half-life, and dozens of other individual characteristics. Scientists have to find ways to elicit the right immune response from people with varying body types. “You need a different playbook for each drug,” Janda says.
And even after a vaccine is developed in the lab, getting it out on the market is another series of hurdles: It’s expensive to prepare the vaccines and bring them to clinical trials, and the stakes are high. After a nicotine vaccine for relapse prevention failed in clinical trials in 2013, Janda said future vaccines have to be nearly bulletproof before sending them out for costly and time-consuming testing: “If you’re going to move something forward, it has to be the Rolls Royce.”
Interested in learning more about the biology of addiction? Kim Janda will be joined by Nora Volkow, Eric Nestler and Amir Levine on Saturday May 31 at “The Craving Brain: The Neuroscience Of Uncontrollable Urges,” part of “The Big, the Small and the Complex” series sponsored by the Kavli Foundation.
By: Lauren Biron
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