Every so often this cocaine vaccine issue rears its head again. I saw it again just the other day. The problem is, of course, the tendency of the media (ain’t it always the media) to say something like “OMG THIS IS TEH CURE FOR EVERYTHING!” in response to one small study. And who knows, the cocaine vaccine may indeed be the cure for everything, but Sci needs to see some big trials before she gets her hopes up. As it is, the studies I have seen provide some interesting clues, but also provide some important warnings.
So, first question first: how the heck do you make a cocaine vaccine?
Haney et al. “Cocaine-specific antibodies blunt the subjective effects of smoked cocaine in humans” Biological Psychiatry, 2009.
As you might know, your immune system can recognize foreign agents (like bacteria or viruses). After it sees them once, it can “remember” the foreign agent, and then when it sees it again, it calls out the cavalry to fight it, hopefully fast enough and in high enough numbers that you never actually feel sick. This is the principle behind vaccination, to get your body to recognize a foreign pathogen and be prepared so you don’t get sick and die from measles or polio.
Foreign agents are usually called “antigens”, which are bound to by specific “antibodies” which are little proteins which stay in the blood in very small amounts, and which are very specific for one kind of antigen . For the cocaine vaccine, this is the important part of the immune system that needs to be activated, the antibodies.
Here’s the deal. Cocaine is not a bacteria or a virus, it’s a chemical. It’s also very small, and passes from the blood through to the brain very easily. But if you can get antibodies to glom on to the cocaine molecule, you can bulk up the molecule such that it will be unable to pass into the brain. The problem is that cocaine is SO small that the immune system doesn’t react to it.
So the scientists who developed the cocaine vaccine got kind of brilliant. They used a cocaine derivative (a molecule related to cocaine) called succinylnorcocaine, which they then attached to a nontoxic small chunk of a cholera toxin. This made the molecule big enough for antibodies to develop to various parts of it, including the part that LOOKS like cocaine. The idea is that then, when the person is exposed to cocaine, the antibodies specific to the cocaine-lookalike part of the vaccine will multiply, glom on to the cocaine molecules, and slow their ability to get into the brain. How high you feel when taking psychostimulants is partially determined by how fast they get to the brain (hence why smoking, snorting, and injecting stuff is a bigger high than eating it, which is a much longer route). And so slowing down the speed at which cocaine can get into the brain, as well as slowing the AMOUNT of cocaine that can get into the brain, may be able to slow down or reduce the rewarding effects of the drug. Studies in rats showed that the vaccine reduced cocaine levels in the brain by as much as 80{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3}, and made it less rewarding. Time to move to humans.
For this study, they picked 10 crack addicts who had no desire to seek treatment. You might think that’s an odd requirement, but actually it makes sense. They wanted to make sure that, if the vaccine caused people to reduce cocaine intake, it wasn’t because people were TRYING to reduce their intake, so they chose people who didn’t want to quit. So they had 10 dudes who spent an average of $284 per WEEK on cocaine (and you thought cigarettes were expensive). The patients were given the cocaine vaccine in an injection four times over 13 weeks.
The authors then looked at the antibody levels for cocaine in the blood up to a year following the first vaccine administration. High antibody levels might predict the effectiveness of the vaccine. Unfortunately, the vaccine gave very different antibody levels, regardless of whether they used a low or high dose, depending on the patient. They then took the patients that had been given the vaccine and exposed them to cocaine, asking them how they felt, how “good” they thought the drug was, and checking their heart rate.
And as long as they had high antibody counts, the vaccine appeared to have an effect:
You can see here that the people with large antibody counts (left panels) felt that the coke they smoked was of lower quality and didn’t feel as good, while those with the lower antibody counts didn’t notice a difference. Not only that, these study participants were outpatient, and those with high antibody counts reported less drug use as the study continued.
So far, this seems all well and good, and if you can get a high antibody count, you may be able to reduce the amount of drug people are taking. This may not do much for those who are not trying to quit, but for those who are, getting less of a drug effect might make quitting a little easier. It makes cocaine feel less good, and that’s good, and even BETTER, it’s not a pill you have to take. For example, there are many pills alcoholics can take that will make them feel ill when they drink. The result, unfortunately, is that alcoholics don’t take the pills. The vaccine for cocaine, on the other hand, is an injection. You make the decision to go in one, two, or three times, and then you can’t undo it when you want to do some coke a few days or weeks later. So you could give the vaccine to patients who are being treated inpatient for addiction, and it might help them not to relapse when they get out.
However, there are a couple of things about this study, and about the cocaine vaccine in general, that I think should be kept in mind:
1) The antibody titers varied a LOT, it appears to be really hard to get consistency, and so in some patients, it may be very hard to help them without lots of doses.
2) The vaccine didn’t work for life. Antibody levels were down after a year, so the vaccine might have to be administered once a year or once every six months to really reduce drug use. This isn’t necessarily a problem, but it’s something to think about in terms of cost.
3) This:
This shows the measures of heart rate taken over the study, and what you can see is that the patients with high antibody titers had higher heart rate responses to cocaine, as well as what looks like higher plasma cocaine levels (though that didn’t reach significance).
You might ask why this is a problem. Well, cocaine is a stimulant which increases heart rate and blood pressure. It might be that higher plasma levels and higher heart rate might make patients feel nervous and increase the NEGATIVE effects of cocaine. Unfortunately, it is also possible that, because the people with high antibody levels don’t feel the drug as well, they might try to take more or higher doses of cocaine to make up the difference. If they are getting higher plasma levels of cocaine, and higher heart rates, this could make them more susceptible to ODing on cocaine (people who OD on cocaine often die of heart attacks from the increase in blood pressure).
And of course, an n=10 is awfully small. I’d also like to see what this could do in people who really wanted to quit, if it could help them. Still it seems like a good start and something to pursue. But I wouldn’t say it’s the CURE WE”VE BEEN WAITING FOR yet.
Haney, M., Gunderson, E., Jiang, H., Collins, E., & Foltin, R. (2010). Cocaine-Specific Antibodies Blunt the Subjective Effects of Smoked Cocaine in Humans Biological Psychiatry, 67 (1), 59-65 DOI: 10.1016/j.biopsych.2009.08.031
