TABLE 2.

Summary of menthol’s effects on nicotine use.

Species	Route	Doses	Nicotine pH	Main findings	References
C57BL/6 mice, adult males	Oral	Menthol (10–200 μg/ml) Nicotine (50–200 μg/ml)	“Base”	• Male mice prefer mentholated nicotine solutions (50 μg/ml menthol, 200 μg/ml nicotine) over nicotine alone in two-bottle choice task	Fan et al., 2016
Sprague Dawley rats, adult males	Oral, intravenous (i.v.)	Menthol (0.005% w/v) Nicotine (0–100 mg/L; 30 μg/kg/infusion)	*Oral-7.4 *i.v.- free-base	• Rats increase oral nicotine consumption (50, 100 mg/mL) when menthol present compared to nicotine alone in two-bottle choice task	Wickham et al., 2018
				• Rats do not increase lever pressing for i.v. nicotine delivery with concurrent intraoral menthol delivery
Sprague Dawley rats, adolescent females	Oral, i.v.	Menthol (0.01% w/v) Nicotine (30 μg/kg/infusion)	7.0–7.4	• Rats increase responding (licking at active spout) for i.v. nicotine delivery with a concurrent intraoral menthol compared to i.v. nicotine with intraoral vehicle	Wang et al., 2014
Sprague Dawley rats, adult males and females	Oral	Menthol (100–1,000 mg/L) Nicotine (3, 20 mg/L)	Free-base	• Only male rats show an increased consumption of menthol-containing solutions in two-bottle choice task	Bagdas et al., 2020
C57BL/6J mice, adolescent and adult males and females	Oral	Menthol (10 μg/ml) Nicotine (200 μg/ml)	7	• Only adult male mice increase oral nicotine consumption when menthol is added to drinking solution	Fait et al., 2017
Sprague Dawley rats, adult males and females	Oral	Menthol (50 μg/ml) Nicotine (0–30 μg/ml)	7	• Menthol increases hedonic responses (tongue protrusions, rhythmic mouth movements) to nicotine (30 μg/ml) in males	Bagdas et al., 2021
				• Menthol decreases aversive responses (head shakes, forelimb flails, gaping) to nicotine (30 μg/ml) in males
Human, N = 32, 50% male, age 18–45	Inhalation	Menthol (0–3.5%) Nicotine (0–24 mg/ml)	n/a	• Participants rate menthol-containing e-cigarettes (3.5% menthol, 24 mg/ml nicotine) as less harsh than nicotine-only e-cigarettes	Rosbrook and Green, 2016
Human, N = 32, 66% male, age 18–50	Inhalation	Menthol (3.5%) Nicotine (0, 24 mg/ml)	n/a	• Menthol reduces ratings of aversiveness and dislike of 24 mg/ml nicotine e-cigarettes	Devito et al., 2020
Human, N = 60, 48% male, age 16–20	Inhalation	Menthol (0–3.5%) Nicotine (0–12 mg/ml)	n/a	• A high concentration of menthol (3.5%) increases liking of 12 mg/ml nicotine e-cigarettes	Krishnan-Sarin et al., 2017
				• Low (0.5%) and high (3.5%) menthol concentrations improve ratings of 12 mg/ml nicotine e-cigarette taste
Human, N = 49, 63% male, age 16–20	Inhalation	Menthol (n/a) Nicotine (6, 12 mg/ml)	Free-base	• Menthol has no effect on taste palatability	Jackson et al., 2021

*Reported nicotine pH differs between administration routes.