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Thursday, October 8, 2009

A Vaccine For White Line Fever?

A study claims that it's possible to immunize against cocaine: Cocaine Vaccine for the Treatment of Cocaine Dependence in Methadone-Maintained Patients. But does it work? And will it be useful?
The idea of an anti-drug vaccine is not new; as DrugMonkey explains in his post on this paper, monkeys were being given experimental anti-morphine vaccines as long ago as the 1970s. This one has been under development for years, but this is the first randomized controlled trial to investigate whether it helps addicts to use less of the drug.

Martell et al, a Yale-based group, recruited 115 patients. They all used both cocaine and opiates, and were given methadone treatment to try to reduce their opiate use. The reason why the authors chose to focus on these patients is that the methadone keeps people coming back for more and makes them less likely to drop out of the study, or as they put it, "retention in methadone maintenance programs is substantially better than in primary cocaine treatment programs. We also offered subjects $15 per week to enhance retention."

The vaccine consists of a bacterial protein (cholera toxin B-subunit) chemically linked to a cocaine-like molecule, succinylnorcocaine. Like all vaccines, it works by provoking an immune response. The bacterial protein triggers the production of antibodies, proteins which recognize and bind to specific targets.

In this case, the antibodies bind cocaine (anti-cocaine IgG) because of the succinylnorcocaine in the vaccine. Once a molecule of cocaine is bound to the antibody, it's effectively out of commission, as it cannot enter the brain. So, the vaccine should reduce or abolish the effects of the drug. The control group were given a dummy placebo vaccine.

The results? Biologically speaking, the vaccine worked, but in some people more than others. Out of the 55 subjects who were given the active vaccine, all but one produced anti-cocaine IgG. However, the amount of antibodies produced varied widely. Also, the response was short-lived. The vaccine was given 5 times over the first 12 weeks, but antibody levels did not peak until week 16, after which they fell rapidly.
And the key question - did it reduce cocaine use? Well, sort of. The authors measured drug use in terms of the proportion of urine samples which were cocaine-free. In the active vaccine group, the proportion of drug-free urine samples was higher over weeks 9 to 16, when the antibody levels were high, and this was statistically significant (treatment x time interaction: Z=2.4, P=.01). As expected, the benefit was greater in the people who made lots of antibodies (43 μg/mL) (treatment x time interaction: Z=4.8, P less than .001). But the effect was pretty small:

The bottom line was about 10% more urine samples testing negative, and even that was only true in the minority (38%) of people who responded well to the vaccine! Not very impressive, but on the other hand, the number of drug-free urine tests is a very crude measure of cocaine use. It doesn't tell us how much coke the patients used at a time, or how many times they used it per day.

Also, bear in mind that if it works, this vaccine might increase cocaine use in some people, at least at first. By binding and inactivating some of the cocaine in the bloodstream, the vaccine would mean you'd need to take more of the drug in order to feel the effects. It's curious that the authors relied on just one crude outcome measure and didn't ask the patients to describe the effects in more detail.

So, these are some interesting results, but the vaccine clearly needs a lot of work before it becomes clinically useful, as the authors admit - "Attaining high (43 μg/mL) IgG anticocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated subjects attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters." Quite an admission given that this study was partially funded by Celtic Pharmaceuticals, who make the vaccine.

It's also questionable whether any vaccine will be truly beneficial in treating cocaine addiction. Such a vaccine would be a way of reducing the temptation to use cocaine. In this sense, it would be just like naltrexone for heroin addicts, which blocks the effects of the drug. Or disulifram (Antabuse) for alcoholics, which makes drinking alcohol cause horrible side effects. Essentially, these treatments are ways of artificially boosting your "self-control", and they work.

But we've had naltrexone and disulifram for many years. They're cheap and safe. But we still have heroin addicts and alcoholics. This is not to say that they're never helpful - some people find them very useful. But they haven't eradicated addiction because addiction is not something that can be cured with a pill or an injection.

Addiction is a pattern of behaviour, and medications might help people to break free of it, but the causes of addiction are social, economic and psychological as well as biological. People turn to drugs and alcohol when there's nowhere else to turn, and unfortunately, there's no vaccine against that.

ResearchBlogging.orgMartell BA, Orson FM, Poling J, Mitchell E, Rossen RD, Gardner T, & Kosten TR (2009). Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Archives of general psychiatry, 66 (10), 1116-23 PMID: 19805702

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