by James J. Galligan,  Ph.D., Associate  Chair,
Department of Pharmacology and  Toxicology

Cigarette smoking is one of the most difficult addictions to quit.  This is partly because nicotine so effectively stimulates the brain’s dopamine reward pathway and partly because cigarettes are so accessible.  The costs to individuals and to society associated with nicotine addiction are enormous.  These costs include shortened life spans, reduced quality of life due to a decline in health and also increased healthcare expenses.  There is great interest in developing treatments that would help nicotine addiction subjects to kick the habit.  There are several choices available right now. These include “The Patch”, Zyban/Wellbutrin (buproprion) and Chantix (varenicline).

The Patch is a step down system in which the individual applies nicotine containing patches to the skin.  The nicotine is absorbed from the patch and the nicotine supplied by this approach reduces the craving for cigarettes.  Over several weeks, the individual reduced the “dose” of nicotine until they no longer experience nicotine cravings.

buproprionBuproprion is a complicated drug that acts as an antagonist for the receptors for nicotine and it is a dopamine and norepinephrine reuptake inhibitor.  Buproprion blocks the rewarding actions of nicotine by blocking the nicotinic receptor.  Buproprion also activates the endogenous reward pathway by increasing the availability of norepinephrine and dopamine in this pathway.


Varenicline is also an antagonist of the nicotinic receptor in the reward pathway in the brain.  These drugs all reduce the reward associated with cigarette smoking and this makes it easier to kick the habit.  These drug treatments all have reasonable success rates with up to half of the subjects off cigarettes after 4-12 weeks of treatment.  However, the relapse rate is high after the smoking cessation treatment is stopped and about 90% of people are back on the cigarettes at 1 year.

The problem described above has spurred interest in the development of nicotine vaccines.  This requires multiple nicotine treatments which activate the immune system to produce antibodies against nicotine.  This is an extremely useful strategy as the treated individual becomes immune to the rewarding effects of nicotine.  Antibodies bind to nicotine preventing its movement into the brain where nicotine acts to stimulate the reward system.  Relapse rates would be lower as the individual is permanently immunized against nicotine.  Recent clinical trials of NicVax, a nicotine vaccine, have yielded very positive results ( and treated subjects have been able to maintain abstinence much longer than placebo treated groups.

These preliminary results are promising but the outcome of the full trial is still about 1 year away.  If the data from the final study match data from the preliminary results then it may be possible to immunize current cigarette smokers with the goal of getting them to kick the habit in the long-term.


Nathan R. Tykocki
Graduate Student, Pharmacology and Toxicology

I know all-to-well the addictive powers of cigarettes, and trying to quit is a Sisyphean task to say the least.  The hardest thing to overcome are those cravings – the need to have the pleasure caused by lighting up.  But now a new option exists to combat that drive to smoke, and it’s not what you would think.

NicotineNicotine (ironically similar to niacin, an essential human nutrient), can cross the blood-brain barrier and ultimately increase dopamine levels in the reward circuits in the brain.  This increase in dopamine leads to relaxation, euphoria, and the continued urge to smoke.  Repeated nicotine use causes a downregulation of dopamine synthesis, but becomes more sensitive to nicotine’s ability to release dopamine in the reward pathways in the brain.  Thus, the “lows” are lower, the “highs” are higher, and a bad habit rapidly becomes an addiction shared by more than 44 million Americans.

Current pharmaceuticals used to aid in smoking cessation work in the brain in two ways: drugs like bupropion (“Zyban”) that help maintain the levels of dopamine in the brain to prevent the between-smoke “lows”, or those like varenicline (“Chantix”) that decrease the sensitivity to nicotine and prevent the during-smoking “highs”.  While these drugs have been shown clinically to decrease the rate of smoking versus placebo in the short-term, they both come with a myriad of unpleasant side-effects that decreases patient compliance and lower long-term cessation dramatically.  Nausea, vomiting, lethargy, and vivid dreams (and trust me – the dreams can be V-I-V-I-D!!)  make cigarettes seem not-so-bad in comparison.  So what can we do??

Here’s where the new idea comes in.

NicVAX (click image to visit microsite)

Instead of fighting the effects caused by nicotine, a new drug called NicVAX (currently in stage III clinical trials) combats nicotine itself.  In fact, the drug doesn’t work in the brain at all!  According to the company’s website, NicVAX stimulates the body’s immune system to create antibodies against nicotine.  These antibodies will specifically recognize nicotine and bind to it, forming a complex that is too large to cross into the brain and activate the reward centers associated with smoking.  In short: no reward equals decreased smoking.  Because this new drug stimulates the body to produce antibodies against nicotine, it may work much longer than traditional smoking therapies which lose their efficacy relatively rapidly if use is discontinued.  Since it is a vaccine, the body will continue making antibodies to nicotine for 6-12 months after initial drug treatment.  The most interesting bit about this drug is the extremely low incidence of side-effects.  Since it does not work to counter the effects of nicotine in the brain, there are apparently very few psychological side-effects.  This increases patient compliance, and will hopefully lead to greater long-term cessation success.

Now if only there were a jelly doughnut vaccine…

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