Using Antibodies to Fight Addiction

April 23, 2010 in Medicine by RangelMD

Antibodies are complex proteins created by immune cells that are targeted to very specific parts of other large and complex molecules called antigens. Much smaller molecules like nicotine, called haptens,  do not normally induce any significant immunologic response so researchers chemically bound several nicotine molecules to a large protein to form an adduct. This combined molecule does induce an immune response, i.e, causes  immune cells to produce antibodies targeted to the nicotine molecule. So the next time the patient smokes or otherwise uses a tobacco product, these antibodies bind to nicotine and prevent it from crossing from the blood stream into the brain where it would normally bind to receptors that are responsible for the psychotropic effects of nicotine including addiction.

A nicotine vaccine that uses this mechanism to treat tobacco abuse and nicotine addiction has shown good efficacy in early results from phase III trials. Of the patients who had taken the vaccine, 16% had stopped smoking one year later compared to 6% who were given a placebo. This is actually pretty good for a substance that is both physically as well as psychologically very addictive. And not all of the nicotine ingested from each tobacco dose is blocked and there are significant behavioral and psychological issues that weigh heavily on the success of smoking cessation. Yet, the fact that this vaccine works at all is a huge breakthrough in addiction treatment. We could see the development of vaccines for use in the treatment of narcotic and amphetamine addictions.

It will also be interesting to see if practitioners start combining the use of this vaccine with the two novel drug treatments for tobacco addiction currently on the market. Bupropion (Zyban or Welbutrin) is an antidepressant that increases  noradrenergic and dopaminergic release (neurotransmitters) in the brain. In a randomized, double blind study, at one year 23% of those who had been treated with bupropion for 12 weeks had quit vs 12% who took a placebo. Varenicline (Chantix$$) is unique in that it binds to the receptor for nicotine in the brain (the alpha4beta2 subunit of the nicotinic acetylcholine receptor). But varenicline only partly binds to the receptor so in theory causes just enough nicotine effect to decrease nicotine withdrawal symptoms while preventing the nicotine from tobacco from binding and causing the full nicotine effect. Varenicline daily dosing for 12-24 weeks has been shown to be equal to or better than bupropion in several studies and three times better than placebo in leading to a smoking cessation rate at 12 months.

In theory, this vaccine should be very safe and actually have far fewer side effects than bupropion  which can cause insomnia, agitation, dry mouth, and headache and  even seizures in rare cases and both bupropion and varenicline may cause suicidal thoughts and aggressive and erratic behavior in some patients. Look for studies that combine the vaccine with bupropion or varenicline treatments to see if there is any additive effect. In theory, you wouldn’t want to use nicotine replacement therapy (the patch, gum, nasal spray, etc) in combination with the vaccine since the increase in antibodies will have blunted the effect of this type of treatment. Though there is concern that patients may try and smoke more after getting the vaccine in an effort to compensate for the decreased nicotine effect. If this becomes a problem then nicotine replacement therapy may still have a role in being combined with vaccine treatment. It’s safer to use a patch than to smoke.

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