Researchers have demonstrated a practical approach for treating nicotine dependence. Currently Nicotine Replacement Therapy (NRT) - nicotine patches or lozenges - relies on providing additional nicotine to the body. Researchers have now turned to nicotine’s oxidative metabolite, cotinine. Using ascorbic acid as a potential reducing agent, they converted cotinine in smokers’ plasma back to nicotine, targeting both nicotine addiction and detoxification simultaneously.
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Publishing the results of their study, Recirculating bioavailable nicotine metabolite using ascorbic acid : A pragmatic approach to treating nicotine dependence, a team of researchers from the Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, have developed a dissolvable film containing Vitamin C that a smoker places on the tongue whenever tempted to smoke. Ascorbic acid in a specified dose (Vitamin C) converts cotinine back to nicotine within the smokers’ plasma, they claim.
Individuals find it difficult to quit smoking because of nicotine withdrawal. Current NRT products provide additional nicotine to the body. This turned researchers to cotinine. The results of the study were published in the indexed journal Advances in Redox Research. The team has filed for an Indian patent and has established an incubator for clinical application.
According to Murugesan Arumugam, first author: “Nicotine is metabolised into cotinine, an oxidative metabolite. Cotinine will stay in the body for six weeks (the quantity of cotinine depends on an individual’s tobacco consumption). Generally, 80% of nicotine accumulates as cotinine in the body, while the remaining 20% is eliminated in urine. Cotinine can cause cancer. So, for the first time, instead of adding on to the nicotine content in the body, we have showcased that vitamin C can be utilised to recirculate cotinine. Side effects are negligible, the person does not receive additional nicotine and detoxification occurs at the end of the cycle.” Raman Lakshmi Sundaram, Vishal Jayajothi, Manish Arul, Jerad A Suresh and Sathesh Kumar Kesavan are the other authors.
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For the study, the researchers screened and recruited volunteers - both non-smokers and smokers. A total of 41 volunteers were screened of whom 25 met the criteria and were enrolled. All of them were men and had a median age of 21 years. Nearly 64% of the volunteers attempted to quit smoking but were unable to do so because of the severity of their withdrawal symptoms; the major being depression.
The accumulation of cotinine in the body can vary depending on the amount of nicotine consumed. Their objective was to convert cotinine into nicotine by reducing its carbonyl group. They first used a software to identify potential reducing agents and analysed the forward reaction of cotinine with various compounds. Based on their analysis using the software, they found it could be possible to convert cotinine back to nicotine using reducing agents.
They conducted a study on the time and dose dependent effects of ascorbic acid on the conversion of cotinine to nicotine in plasma samples. While three out of the 25 volunteers who consumed beedi or other high-tar-containing tobacco products showed a failure in the conversion of cotinine back to nicotine compared to volunteers who used light cigarettes, the mean conversion of cotinine to nicotine in sample from smokers demonstrated a significant increase in nicotine and a reduction in cotinine after incubation with a specific dose of ascorbic acid. “We found that when the dose of ascorbic acid is higher, conversion rate is low, thereby indicating optimum doses are necessary for the conversion. So, marketed products will not be useful. This is why we have made a thin film containing ascorbic acid for the intervention,” he explained.
The researchers said that the converted nicotine may be recirculated to produce CNS effects, which could help in the treatment of nicotine withdrawal and reduce cotinine accumulation in the body. They, however, noted that further studies with larger sample populations and subsequent behavioural studies were required to confirm these findings.
