Smoking continue to be one of the biggest public health problems. Nicotine work via nicotinic receptors in brain.B2 subunit of this receptor is considered crucial to nicotine’s effects. If we can induce the body to produce anti nicotine antibody that binds to nicotine that would then reduce the amount of nicotine reaching brain. ( the nicotine-antibody complex is too large to cross blood brain barrier). That would mean that less activation of reward centres and thus less craving. Would such a vaccine work as we think?
Esterlis et al.reports the results of a proof of concept study based on the above assumption.The vaccine was 3:aminomethylnicotine conjugated to recombinant Pseudomonas exoprotein A (3:-AmNic-rEPA).This has high affinity for nicotine.
Study: Four to five injections of 400 mg each of this vaccine was given to eleven non-treatment-seeking tobacco smokers. They were scanned (SPECT or receptor binding) before and after four monthly immunisations.Subjects abstained from tobacco for the 5 days before each SPECT scan day to allow for any nicotine or metabolites to clear the brain. ( as they may compete with radiotracer binding). To check whether immunisation has the desired effect, subjects were given IV nicotine and scans were repeated to measure binding to receptors.
There was a significant increase in antibody concentrations over the course of the treatment. A maximal binding of 55% of the b2 subunit was observed before vaccination, which was reduced by 11% after vaccination. Immunization results in 30%–90% less nicotine entering the brain after acute nic- otine exposure. Administration of iv nicotine after immunization was associated with plasma nicotine concentrations at least twice as high as before immunization. Subjects reported 40% reduction in cigarette use and a significant reduction in craving for cigarettes from baseline to completion of immunization.
Limitations:The lack of a placebo control group limits clinical interpretation.Study has only 11 participants.
Comments: 11% decrease in binding seems small and unlikely to affect the reward experienced from smoking enough to result in clinical effects.In the accompanying editorial Fagerstrom and Tonstad comment that smoking is not just about nicotine. However, the concept of vaccines against nicotine is quite interesting though the clinical results so far has not been convincing.
Summary of the article:
Esterlis I, Hannestad JO, Perkins E, Bois F, D’Souza DC, Tyndale RF, Seibyl JP, Hatsukami DM, Cosgrove KP, O’Malley SS. Am J Psychiatry. 2013 Apr 1;170(4):399-407.