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…