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

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 (http://www.cnn.com/2010/HEALTH/04/21/nicotine.vaccine.nicvax/index.html) 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.