Thursday, June 23, 2011

A Nicotine Vaccine Just Might Cure Smoker’s Addiction

Peter Coleman, M.D. 

People love to smoke their cigarettes even though at the exact same time they hate the fact that they smoke.  They decide not to quit even though at the exact same time they would love to quit.  What a paradox this is!  In many ways cigarette smoking is one of the best models we have for the addiction process. It can help us understand the other, (more serious?) addictions we treat - Heroin, Oxycodone, Alcohol and Cocaine. 

Nicotine goes right to the pleasure center of the brain and activates the Dopamine pathways making us feel good and wanting us to keep smoking even when we know it is bad for us.  It can relieve negative feelings we don’t like including loneliness, fatigue, boredom, anger, and anxiety.  Intense cravings for cigarettes can be brought on by triggers in our environment.  Very soon after it is smoked the Nicotine goes to the brain and has all of these very powerful effects.

But what if there was a treatment that forever prevented the nicotine from getting into the brain.  What if there was a medical treatment that permanently would not allow nicotine to have any of these effects on the pleasure center or the other parts of the brain?  Such a treatment is being developed and is showing great promise!

An important thing to know about all drugs of abuse, including Nicotine, is that the molecule has to be small enough to get through the blood brain barrier.  If the molecule is too large it simply can’t get into the brain and so it can’t have any of its effects in the brain.

This is where vaccines come in.  Vaccines force the body’s immune system to make specific antibodies to attach to anything foreign that our body decides is dangerous.  So in order to cure drug addiction a great technique would be to get the immune system to make antibodies that would physically stick to a drug of abuse.  The resulting complex –the drug of abuse with the antibody attached - would be too large to cross the blood brain barrier.  The new complex would not be able to enter the brain.

This idea is not new.  In fact, some research done 40 years ago with morphine showed that rats could be induced into making antibodies against morphine.  These antibodies actually reduced the amount of morphine rats would use and when the same technique was applied in monkeys, similar studies showed the monkeys used less Heroin.

It is not very easy to induce animals to make antibodies to drugs of abuse because the molecules are small and generally not considered very “foreign” to the body.  So scientists have to combine the drug of abuse with something that the immune system considers to be dangerous, and then the immune system will make antibodies quite well.

When it comes to vaccines for cigarette smoking, scientists at three different companies are working to get a product that reliably forces the body to make antibodies in sufficient quantities to bind to Nicotine.  One of the vaccines that has made the most progress is called NicVax, made by Nabi Pharmaceuticals.  Recently I was at a conference where I was fortunate enough to hear a presentation from a company representative.  They have made amazing progress and are getting close to completing their final clinical trial before they submit for FDA approval.  NicVax has combined nicotine with a protein from bacteria called Pseudomonas.  Our bodies don’t like pseudomonas bacteria and our immune systems immediately react and make antibodies to both the pseudomonas component but also to the nicotine component.  These antibodies are then able to bind to nicotine if it is smoked and the nicotine cannot get into the brain.  There are no major side effects with this vaccine.

Results of testing in cigarette smokers are very promising. Patients given NicVax are able to make antibodies against nicotine.  It is necessary to give multiple doses of the vaccine in order to get high levels of antibodies and it can take up to 14 weeks to get these high levels.  The most recent reports indicate that, with a series of 6 shots, around 80% of patients in the trial are able to make high levels of antibodies.  The high antibody levels seem to last well over a year and it is likely that some of these antibodies will remain for life.  Some patients may require booster shots at some point.

The studies clearly show that patients with high levels of antibodies stop smoking fairly well.  Currently the results for these patients show that about 24% of them stop smoking completely for 12 months.  It is most likely this number will increase if patients take more booster shots.  What is most interesting in the studies is that the quitting rate keeps going up as the trial progresses – in contrast with most studies of other smoking cessation products where there is a steady decrease in success as some patients return to smoking.  With NicVax the number of quitters keeps increasing.  This makes sense when you think that with NicVax, patients have the antibodies that prevent them from enjoying cigarettes.  It seems likely that more and more of these patients will readily give up their cigarettes as they realize they are not getting much out of it.  Indeed, the studies show that even for the patients who keep smoking they are still partially successful. These NicVax patients who keep smoking find that their smoking goes down by about 50% as they realize they are not getting much out of it.

I believe Nicotine vaccines will play a powerful role in helping patients quit smoking.  If these vaccines can produce high enough levels of antibodies that last for a lifetime, we really can talk about a cure for smoking.  Once the vaccine has been given there will be no turning back.  I wonder if it will ever bring up an ethical question – should we be giving a treatment that permanently takes away patients option to change their minds. What if they ever want to return to smoking again?

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