Quit Smoking Enzyme Stops Nicotine Addiction in Rats Without Withdrawal Symptoms

An enzyme that could help people quit smoking has been developed by scientists and tested successfully on rats. While its potential to treat human nicotine addiction is some way off, researchers believe it could be developed into a pill that stops smokers missing the drug—and potentially without any withdrawal symptoms.

Scientists performed an experiment in which two groups of rats were trained to self-administer nicotine over two weeks. Their nicotine intake escalated, which indicated addiction.

One of these groups was then given the enzyme and the other was not. Both groups were still able to self-administer nicotine.

Of the enzyme group, rats were given varying levels of the NicA2-J1. This enzyme degrades nicotine meaning levels of the drug area reduced in the blood. Researchers discovered that, at higher levels, the enzyme led to a decreased nicotine intake. The rats also did not display withdrawal symptoms or "irritability-like" behavior.

The findings, published in Science Advances, indicate the enzyme is effective at treating nicotine addiction in animal models—and that it could be further developed for human use in the future.

lab rat
Research into reversing autism is in pre-clinical stages and is mostly carried out in rodents. iStock

It is estimated that almost 28 million adults in the U.S. smoke cigarettes. Around 16 million are currently living with a smoking-related disease, and reducing smoking rates is a major public health issue. Strides are being made, however, as the percentage of cigarette smokers fell from 20 percent in 2005 to 15 percent in 2016. But smoking still remains a big problem across the country. It is estimated that, if current trends continue, 5.6 million children living in the U.S. today will die prematurely from a smoking-related illness.

The research was led by Marsida Kallupi and Olivier George from the Scripps Research Institute in California. George told Newsweek that they will need to perform more research in mice to make sure the enzyme is not toxic and tweak it accordingly if there are any problems. He also said that they are hopeful the enzyme eventually will move forward into human testing.

"So far we haven't seen any major toxic effect so we are very optimistic," he said. "The biggest obstacle is not scientific here, it is actually finding the funding that will allow us to take this approach to the clinic...once the funding is secured I anticipate that we will make very fast progress."

quit smoking
It’s estimated that almost 28 million adults in the U.S. smoke cigarettes. An enzyme that could help people quit smoking has been developed by scientists and tested successfully on rats. iStock

"The idea here would be that smokers who want to quit would take a pill every week or so to maintain high levels of the enzyme in the blood and would continue smoking at first. Because the enzyme will trap most of the nicotine, they will progressively become less and less dependent on nicotine without going through withdrawal and find the cigarette less and less attractive. Our data show that individuals following this protocol would have higher odds of quitting and lower risk of relapsing. Even if they quit completely they would keep taking the enzyme just in case they have a lapse to ensure that it doesn't result in a full relapse."

He said the lack of withdrawal in the rats was a huge surprise. They believe this could have happened because the enzyme lets a tiny trace of nicotine remain in the blood. This could be just enough to stave off any withdrawal symptoms until the level of dependence is negligible.

If this translated into humans it could help smokers skip the withdrawal phase and help prevent relapses. "There are plenty of studies showing that smokers who switch to denicotinized cigarettes do not like them and eventually switch back to their favorite nicotinized cigarette," George said. "The beauty of our enzymatic approach is that the enzyme would make every cigarette denicotinized, there wouldn't be a possibility to cheat as long as you take the pill."

Norman Edelman, Senior Scientific Advisor at the American Lung Association, said the findings were interesting—but that any treatment for humans was still a long way off: "While smoking has reached historic lows through these cessation efforts as well as tobacco prevention and control programs, the reality is that tobacco use remains the nation's leading cause of preventable death and disease," he told Newsweek. "Much more should be done to save the lives Americans, as there is an estimated 480,320 tobacco-related deaths every single year.

"Given the magnitude of the problem, any new and proven effective approach to smoking cessation is welcome. The work outlined in the study looking at lab rats is interesting because it embodies a new approach by administering an enzyme which degrades nicotine in the body thus preventing nicotine from reaching the brain and causing the well-known behavioral and addictive effects. In the rats tested in the study, the drug not only reduced nicotine craving but also seemed to reduce the effects of nicotine withdrawal which is a major problem in smoking cessation regimens. If these effects could be successfully produced in humans, this agent could add significantly to our pool of approaches to smoking cessation.

"However we must note that there is a long way to go before human use can be considered. Potential problems include the following: It would appear that the drug has to be given by injection; it is not clear whether the drug has to be given for long periods to prevent relapse; we really cannot know the full short and long-term side effects of the drug in humans from this animal model. Nevertheless, it is a new approach with some potentially unique advantages and we certainly look forward to continued studies."

This story has been updated to include quotes from Norman Edelman.