Volatile Terpenes and Brain Function: Investigation of the Cognitive and Mood Effects of Mentha × Piperita L. Essential Oil with In Vitro Properties Relevant to Central Nervous System Function

Abstract

Extracts of several members of the monoterpene-rich Lamiaceae sub-family Nepetoideae, including those from the Salvia (sage), Melissa (Lemon balm) and Rosmarinus (rosemary) genera, evince cognitive and mood effects in humans that are potentially related to their effects on cholinergic and GABAergic neurotransmission. To date, despite promising in vitro properties, the cognitive and mood effects of the closely related Mentha spicata (spearmint) and Mentha piperita (peppermint) remain unexplored. This study therefore assessed the human cognitive/mood effects of the M. spicata/piperita essential oil with the most promising, brain-relevant in vitro properties according to pre-trial in vitro screening. Design: Organic spearmint and peppermint (Mentha spicata/piperita) essential oils were pre-screened for neurotransmitter receptor binding and acetylcholinesterase (AChE) inhibition. In a double-blind, placebo-controlled, balanced cross-over study, 24 participants (mean age 25.2 years) consumed single doses of encapsulated placebo and 50 µl and 100 µl of the most promising essential oil (peppermint with nicotinic/GABAA receptor binding and AChE inhibitory properties, that increased calcium influx in a CAD cell neuronal model). Psychological functioning was assessed with mood scales and a range of standardised, cognitively demanding tasks pre-dose and at 1, 3 and 6 h post-dose. Results: The highest (100 µL) dose of essential oil improved performance on the cognitively demanding Rapid Visual Information Processing task (RVIP) at 1 h and 3 h post-dose and both doses attenuated fatigue and improved performance of the Serial 3 s subtraction task at 3 h post-dose. Conclusion: Peppermint (Mentha piperita) essential oil with high levels of menthol/menthone and characteristic in vitro cholinergic inhibitory, calcium regulatory and GABA_A/nicotinic receptor binding properties, beneficially modulated performance on demanding cognitive tasks and attenuated the increase in mental fatigue associated with extended cognitive task performance in healthy adults. Future investigations should consider investigating higher doses.

Keywords: Mentha; cognition; mint; terpenes.

Figure 1

Dose-response radioligand binding properties of M. piperita essential oil (sample 4) in adult rat forebrain membranes at concentrations between, 0.000 and 1 mg/mL using [³H] flunitrazepam, [³H] MK-801 and [³H] nicotine.

Figure 2

Effects of M. piperita essential oil on Calcium mobilisation in differentiated CAD cells. M. piperita essential oil (0.1 mg/mL) was applied (red arrow) and recorded for 250 cycles. Representative of at least 5 cells from 3 separate experiments. (A) Positive modulation on calcium intracellular mobilisation. A rapid increase in calcium was observed in the neuronal cell body, which peaked approximated cycle 40 post-application (approx. 30 s) and then dropped steadily to a level below the original starting concentration at cycle 250. (B) Extension of depolarization—induced calcium mobilisation. In the presence of M. piperita essential oil (0.1 mg/mL) for approx. 180 s, a depolarisation pulse for 250 cycles elicited a rapid calcium increase followed by a delayed decrease compared to a depolarising pulse alone, which desensitised significantly quicker. (C) Representative images. Representative images of individual cell body calcium changes in the presence of M. piperita essential oil (0.1 mg/mL), pre-application, peak of calcium increase and post peak reduction in calcium levels.

Figure 3

Running order of tasks administered during each assessment.

Figure 4

Testing session timeline for all visits.

Figure 5

Effects of peppermint (Mentha × piperita) essential oil on the performance of the Cognitive Demand Battery tasks during the 1 h, 3 h and 6 h assessments. Data are mean (± SEM) % change from pre-dose baseline. Asterisks represent a significant difference to placebo from the a priori planned comparisons. *, p < 0.05; **, p < 0.01.