A vaccine against nicotine for smoking cessation?

And with this post, I welcome the return of my Picasa!  Unfortunately I am not back on my sturdy speedy desktop because my hard drive is STILL down (the replacement is 4 days late), but my ancient little tank of a laptop will have to do.

I study addiction, and whenever we addiction people get together, we talk about pretty much anything BUT nicotine.  Alcohol is big, cocaine is bigger, and speedball (a combination of heroin and cocaine) has been a dark horse of late.  Everyone wants to talk about amphetamines and Ritalin, and opioid addiction is as big as ever.  Even cannabinoids and hallucinogenics (some of which have been used in treatment of migraine, though now we’re finding better drugs) are huge.  But nicotine is often pretty silent. 

There are several reasons for this.  Nicotine acts at the nicotinic receptor, an entirely different mechanism of action from the catecholamines of the stimulants, the opioid receptors of heroin, morphine, fentanyl, and percoset,  and the GABA receptors of alcohol, benzodiazepines, and other downers.  Additionally, nicotine addicts don’t really stand out.  Addicts of almost any other drug, meth, cocaine, heroin, alcohol, all become non-functional in society as their addiction carries them away.  But nicotine addicts exist quietly, coughing and a little smellier than most, but you’ll never see them selling themselves for a cigarette or giving away their children for some Nicorette. 

That said, nicotine as a drug is no laughing matter.  Aside from the cancers, emphysema, and heart problems associated with long term smoking, nicotine is one of the most addictive drugs out there.  It may not have the dramatic addictive effects associated with heroin or meth, but analyzed as number of reinforcements per dose, nicotine averages a whopping ten reinforcements (puffs) per cigarette (that’s average).  And the percentage of people who will try nicotine is far higher than any other drug except alcohol. 

There are lots of smoking cessation programs out there, counseling, nicotine gum and patches, but the number of people addicted to cigarettes who quit and stick with it is fairly low.  The best programs out there can only boast a 15% success rate.  So a group of scientists in Switzerland have been developing a nicotine vaccine.

What would a nicotine vaccine do?  In this case, it is nothing but a sticky glob of protein (a virus-like particle or VLP) with an antibody for the nicotine molecule.  Nicotine is a small chemical that gets through the blood brain barrier and into the brain very easily.  The hope is that, if you give enough of the VLP, it will bind up all the nicotine, making it too bulky to pass through the blood-brain barrier, and so taking away the reinforcing effects.  So hopefully, after getting the vaccine, smoking would not be satisfying.  However, the vaccine is not a curative, people will still have withdrawal and severe cravings that would have to decrease over time.

The vaccine has been tested in animals, where it was found to decrease addiction to nicotine (according to Malin, 2001), and stop nicotine treated animals from going back to the drug (something we call reinstatement, Lindblom, 2002).  After a smaller trial to determine what doses were tolerated and ether or not antibodies appeared as they should (Maurer, 2005), they moved up to a huge trial in humans. 

The good news is that the drug was well tolerated, with minimal side effects, mostly flu-like reactions to the vaccine which lasted less than 24 hours.  But unfortunately, the vaccine did not appear to work.  At month 2, there was an encouraging difference between vaccine and placebo in the number of people who stayed abstinent.  Unfortunately, this didn’t persist over six months, and at the end of the trial, about the same number of vaccine and placebo participants stayed abstinent.

Effects of Nicotine-QB antibody titer and counseling on smoking cessation

But that’s not to say that this trial didn’t find anything.  What they did find was that the vaccine had the greatest effect in people who had the highest antibody titer.  In other words, at the highest reaction to the vaccine (when you produce a lot of antibodies), the patients were binding up the most nicotine, and this had a positive effect on their smoking cessation.  Unfortunately, most patients did not achieve the levels of antibody in their systems required to produce effects of smoking cessation.  So clearly, they need to get higher antibody titers, which I’m sure is something they’re aiming for in future.

Also, all the patients in the study got smoking cessation counseling, even if they were not getting a vaccine, so it’s possible that that may have had some effect on the relatively high abstinence rates that they got (around 30% over a 6-month period). 

It’s my opinion (not that I’m at ALL an expert on either nicotine or vaccines, but I always have an opinion) that perhaps they’re targeting the wrong group of people if they are targeting people who are already smokers, and thus already addicted to nicotine.  The vaccine (they call it Nicotine-QB) sequesters nicotine to prevent reinforcing effects from getting to the brain.  Though this will certainly mean that smokers won’t feel the nicotinic effects of smoking in the brain, they will also have other psychological manifestations associated with smoking.  And they will be certainly feeling the effects of withdrawal, which probably won’t help their smoking cessation.

I think that this vaccine would work best if given in a preemptive fashion, prior to the start of smoking (in the same way that, say, a measles vaccine is given prior to exposure to the measles virus).  I would personally like to see a clinical trial where the vaccine or its placebo is given to a large number of, say, college freshmen, with the number of people who have become chronic smokers is assessed four years later.  I think that this would determine whether sequestration of nicotine by the vaccine would be enough to top the development of addiction in humans. 

Whether this study could be done, I don’t know.  You would probably be unable to do it blind (you have to let the patients know what they’re getting, not doing so is unethical).  Also, would a nicotine vaccine be widely accepted?  The concept of a vaccine against an addiction might upset a lot of people who consider addiction to be a problem of willpower.  The idea is that you shouldn’t HAVE to be vaccinated against an addiction if you have the willpower to resist taking the drug in the first place.  Unfortunately, we have ample evidence that people either do not have that willpower, or feel that they are different and will not become addicted.  Still, should people be vaccinated against something that is essentially voluntary?  You could make the argument that, in the case of the HPV vaccine, sex is voluntary, but it also depends on other people.  You never know whether your partner (who you may have waited to have sex with until your marriage was consecrated in the eyes of somebody) has HPV.  On the other hand, smoking only requires you.  Thoughts, anyone?

Cornuz, J., Zwahlen, S., Jungi, W.F., Osterwalder, J., Klingler, K., van Melle, G., Bangala, Y., Guessous, I., Müller, P., Willers, J., Maurer, P., Bachmann, M.F., Cerny, T., Goodyear, M. (2008). A Vaccine against Nicotine for Smoking Cessation: A Randomized Controlled Trial. PLoS ONE, 3(6), e2547. DOI: 10.1371/journal.pone.0002547

2 Responses

  1. Thanks for the information on a possible vaccine to nicotine. I didn’t know it was so different from other drugs.

    We recently wrote an article on smoking at Brain Blogger. Recently, a lot of areas across the globe have banned smoking in public areas. Is this right; is smoking really that much of a problem? Is so much of a problem that Brazil must take their ad campaigns to a disturbing level?

    We would like to read your comments on our article. Thank you.


  2. Perhaps the vaccine should involve a series of shots, like those required for the hepatitis vaccine. From an immunologic perspective, if you were able to develope a secondary immunologic response, the results as far as antibody titre would be much greater. The trade-off would most likely be an increase in side effects.

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