September 9, 2013 | 3
Effective treatments for drug addiction have been hard to come by. There’s behavioral interventions, methadone maintenance for heroin users, nicotine patches for smokers, antabuse for acoholics, but while all of these are effective in a minority of users, they aren’t effective in all. Many require repeat behaviors that are difficult for addicts. As examples: getting to the methadone center every day can be difficult if you have bad transportation. Alcoholics often need to go to AA meetings several times a week if not several times a day. Antabuse make you feel like crap when you drink…and all you have to do is NOT take it. Nicotine patches don’t tend to scratch the smoking itch in the same way. In the case of cocaine, where is there no drug intervention option at all, when you have someone who is in serious danger of overdose, you need something to take away the effects of the cocaine. Something to work immediately.
Enter the idea of a vaccine against cocaine. For those used to thinking about vaccines as things that fight chicken pox and whooping cough, the idea of a vaccine against a drug can seem a little foreign. But it’s a concept that’s been in development for some time. Not so much in the context of vaccinating against potential cocaine use, but as a way to help people get off the drug. But the question still remains: will it work?
Wee et al. “Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects” Neuropsychopharmacology, 2012.
The idea is to use a vaccine made of a drug that is very close to cocaine (norcocaine), combined with an inactivated virus. The presence of the virus causes the body’s immune system to try and fight it off, creating antibodies to different parts of the molecule, both the cocaine part and the virus part. The antibodies serve as a signal for other immune cells to come along and gobble up the cocaine. After the original vaccine is gone, the antibodies stay circulating in your blood, ready to attack is they see the cocaine signal again.
In the case of viruses, a vaccine would create antibodies that wait for the virus to appear, making other cells gobble it up before you had a chance to get sick. This is why, for example, you never get Chicken Pox twice (or, indeed, since the advent of the vaccine, never get it in the first place). In the case of cocaine, the antibodies would activate the immune system to gobble up cocaine molecules before they could get into your brain, meaning…you would never get high (or possibly, not AS high. Cocaine, especially when smoked as crack, gets into the brain extremely quickly, which means it probably just blunts the high. We’ll get to this more later).
The idea is that when you give a cocaine vaccine to an addict, the antibodies would remain around a long time, making it hard for the addicts to ever get high, and thus (hopefully), making it easier to stay off cocaine all together. In theory, you could also give the vaccine to at risk populations, people who might be at risk for addiction, to reduce the likelihood of becoming addicted.
But does it work? To find this out, the authors of the paper looked at this particular cocaine vaccine (several have been created over the years, one of which is going to clinical trials soon) in rats. They gave three doses of vaccine and looked for how many antibodies were created, and how long they stayed around. They were able to show that the antibodies remained in the blood for about 4 months after vaccination. They also looked at how the rats responded to cocaine after vaccination.
Above you can see control rats (grey) and vaccinated rats (black), who were given a single injection of cocaine. The authors measured how much cocaine was present in the brain and in the blood after the injection. In the control rats, the cocaine went quickly into the brain (you can see how high it is on the left), but in the vaccinated rats, the cocaine was sequestered in the blood (see how high the black bar is on the right). This means that, after vaccination, LESS cocaine was getting into the brains of the rats.
But what about behavior? First, the researchers looked at something called cocaine sensitization. Cocaine is a stimulant, and when people (and rats) are given cocaine, they move around more. If you give cocaine in the same environment, once a day for about 5 days, and then give it again a few days later, you will see sensitization, where they move a LOT more than they did in response to the first dose. This behavior is thought to be an early step in the development of cocaine abuse and addiction.
So do rats given vaccines against cocaine show sensitization like normal rats?
What you can see above is measures of movement in rats given cocaine, rats given the vaccine and THEN cocaine, and rats given nothing (the open triangles). The rats given cocaine (black circles) showed sensitization, you can see the distance they traveled rising every day. But in rats given the vaccine (black squares), the effect was blunted, the rats didn’t show so much sensitization.
This is all well and good, but the best measure would be to see how the rats dose themselves. Drug self-administration is a gold standard in the addiction field, where rats are given a port into a vein, and allowed to press a lever. A certain number of presses will give them a shot of cocaine. The rats pick it up very quickly, and modifications to the paradigm allow you to test how hard a rat is willing to “work” for cocaine, what happens when cocaine is no longer present in the syringe, etc, etc.
What you can see here is the number of injections per hour that the rats gave themselves. You can see that the vaccine treated rats (dark circles), self-administered less cocaine than their control counterparts.
So it looks like the vaccine is able to reduce the effects of cocaine in rats. This means that, in humans, it might make cocaine less rewarding to have, and help enable users to quit.
One thing that is concerning about these vaccines is that it’s possible, in humans, that if they are not getting the “high” they want, they might try and take more to get there, which would increase the odds of an overdose. In the rats, they did not see this compensation, which is good, but I do wonder if that’s because the animals were trained to self-administer cocaine after they already had the vaccine. With the vaccine already on board, they may never have known how “good” cocaine could be, and so wouldn’t “know” to try for a better high. This might be the case, it might not, it would require another study, either in animals or humans, to find out.
But it’s an interesting idea, using a vaccine. I’m interested to see how the clinical trials will turn out, and what they end up finding. While it will take choices and work for an addict to stay off drugs, sometimes a little boost, possibly like that provided by the vaccine, could make the difference.
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