E-cigarette aerosols combining menthol and nicotine produced stronger physiological responses and higher blood metabolite levels in animal models.


RT’s Three Key Takeaways:

  1. Active Flavor Interaction: Menthol functions as more than a passive flavor additive by enhancing both the strength and duration of inhaled nicotine effects, according to a preclinical study.
  2. Prolonged Physiological Impact: Exposure to aerosols containing both menthol and nicotine prolonged body temperature drops in animal models, with significant differences persisting at 120 minutes post-exposure compared to nicotine alone.
  3. Increased Nicotine Metabolites: The combination of menthol and nicotine resulted in higher concentrations of specific nicotine metabolism by-products in the bloodstream than exposure to nicotine-only aerosols.


Menthol, a common additive used in traditional cigarettes and electronic nicotine delivery systems, does more than provide a cooling sensation or alter flavor, according to research published in ACS Chemical Neuroscience. In animal models, male rats exposed to menthol-containing e-cigarette aerosols experienced the physiological effects of nicotine more intensely and for a longer duration than those exposed to nicotine alone, the study authors reported.

While prior research has shown that menthol can alter nicotine-related biological and behavioral responses, relatively little data has existed regarding how menthol alters nicotine dynamics when both substances are delivered simultaneously through an aerosol, according to the researchers. To evaluate this relationship, investigators Seong Shoon Yoon, Sooyeun Lee, and colleagues examined the physiological and metabolic effects of combined inhalation.

“The most important takeaway is that menthol should not be viewed merely as a passive flavor additive,” said Yoon, study author, in a news release. “Our findings in male rats show that it changes both the intensity and the duration of nicotine’s physiological and internal drug-cue effects.”

Study Design and Physiological Findings

The investigators formulated custom e-cigarette liquids containing nicotine and menthol as the sole flavoring agent, according to the published report. The team tested the aerosol formulations across 81 male rats placed in clear exposure chambers. Using a commercial e-cigarette delivery device, investigators administered nicotine, menthol, or combined aerosols at five-minute intervals, adjusting puff counts depending on the specific trial protocol.

Following inhalation exposures, the research team analyzed blood samples for nicotine and its metabolic by-products. The investigators also monitored changes in core body temperature, an established physiological indicator of nicotine activity in rodent models.

When compared against exposure to nicotine alone, the combination of menthol and nicotine:

  • Prolonged the nicotine-induced decline in core body temperature, maintaining statistically significant differences between groups at 120 minutes following aerosol exposure.
  • Increased the internal noticeability of nicotine’s pharmacological effects in the test subjects.
  • Produced higher circulating concentrations of select nicotine metabolites in the bloodstream.

The study authors noted that these findings offer new insight into how inhaled flavor additives can modify nicotine pharmacokinetics and physiological uptake, factors relevant to respiratory clinicians and healthcare professionals evaluating vaping risks and smoking cessation strategies.

Following these results, the researchers plan to investigate the specific biological pathways through which menthol alters nicotine signaling in the brain, as well as whether these outcomes vary between male and female subjects.