Menthol as an additive to cigarettes has been widely successful in keeping smokers smoking. While overall smoking among the population has decreased, the rate of menthol cigarette smoking has stayed pretty much the same, according to a review released on Tuesday about menthol's addictive properties in cigarettes.

The Food and Drug Administration (FDA) also released, on Tuesday, an Advanced Notice of Proposed Rulemaking (ANPRM), which stated that the agency is "seeking additional information to help the agency make informed decisions about menthol cigarettes."

Menthol's Effect On Nicotine Receptors In The Brain

A review, released today, suggests that menthol's chemical properties could play a role in the brain's reaction to nicotine.

"Studies have demonstrated a role for menthol in the metabolism of nicotine in the body," Nadine Kabbani, a neuroscientist at the Krasnow Institute for Advanced Study of George Mason University in Fairfax, Va., wrote. "More recent findings now reveal an interaction between menthol and the nicotinic acetylcholine (nACh) receptor in cells. This receptor is central to the actions of nicotine in the brain, and plays an important role in nicotine addiction."

Kabbani reviewed a number of studies that suggested the effect of menthol on nACh receptors could contribute to cigarette addiction by not only prolonging nicotine's presence in the body, but by also increasing it.

Studies have shown that prolonged cigarette smoking has been associated with increased nACh receptor density in the brain. Kabbani said that this process of up-regulation is likely to contribute to nicotine addiction, since it involves a tendency to self-administer nicotine. Essentially, the presence of more nACh receptors in the brain results in more smoking, creating a cycle of increased addiction. But menthol cigarette smokers showed an even higher level of up-regulation in nACh receptors compared to non-menthol cigarette smokers. Specifically, menthol cigarette smoking was associated with a 9-28 percent rise in nACh receptors in brain regions such as the prefrontal cortex and the corpus callosum.

Menthol was also found to decrease the responsiveness of nACh receptors to nicotine, but did so in a way that only prolonged the effect of the nicotine, rather than stopping the receptor from responding altogether.

Nicotine enhances dopamine levels, and can also regulate the release of glutamate and GABA, two neurotransmitters of the nervous system. When nicotine reacts with nACh receptors in the brain's nucleus accumbens, hippocampus, amygdala, and prefrontal cortex, it can affect memory and decision making, which play a part in addiction. If menthol can alter the function of nACh receptors, Kabbani said, then it's possible that it also alters the addictive properties of nicotine in the brain, however, she admits that more research is needed.

"This is a very important scientific discovery because if menthol does alter the actions of nicotine on its target receptor in the brain, then it is very likely to contribute to nicotine addiction," she said.

She said that possible ways of looking into these connections included rat studies in which the "administration in rodents will enable the assessment of dopamine (and glutamate release) in the brain following the administration of nicotine or nicotine with menthol." Genetic testing into the differences between nACh receptor genes in smokers may also uncover clues as to why certain races are more prone to menthol cigarette addiction.

Possible Public Health Intervention: FDA Reviews Menthol Cigarettes

"Menthol cigarettes raise critical public health questions," FDA Commissioner Margaret A. Hamburg, said in the statement. " The FDA is committed to a science-based approach that addresses the public health issues raised by menthol cigarettes, and public input will help us make more informed decisions about how best to tackle this important issue moving forward."

For 60 days, the ANPRM will be available for public comment. The agency is looking for any data, research, or information that can help them make informed regulatory decisions regarding menthol cigarettes.

In a preliminary evaluation of the possible health effects, initiation, addiction, and cessation of menthol versus non-menthol cigarettes, the FDA said:

"While there is little evidence to suggest that menthol cigarettes are more or less toxic or contribute to more disease risk to their user than non-menthol cigarettes, adequate data suggest that menthol use is likely associated with increased smoking initiation by youth and young adults. Further,the data indicate that menthol in cigarettes is likely associated with greater addiction. Menthol cigarette smokers show greater signs of nicotine dependence and are less likely to successfully quit smoking."

The agency also cited menthol's "cooling and anesthetic properties" for reducing the harshness and flavor of cigarette smoke when inhaled, as well as the marketing, which portrays them as a smoother alternative to non-menthol cigarettes. Young and black smokers were also the most drawn to these types of cigarettes.

Source: Kabbani N. Not so cool? Menthol's discovered actions on the nicotinic receptor and its implications for nicotine addiction. Frontiers in Neuropharmacology. 2013.