05/05/2026
The olfactory nerve represents a unique pharmacological window to the brain, bypassing the blood-brain barrier. Molecules absorbed across the olfactory epithelium can travel along olfactory neurons into the olfactory bulb and adjacent brain regions via intracellular transport and perineural diffusion, allowing some drugs, toxins and volatile compounds to reach the brain more rapidly and certainly than through the systemic circulation. This intranasal-olfactory route is now recognised in neuropharmacology as a potential delivery pathway for central nervous system therapeutics, as well as a mechanism by which environmental exposures can directly influence brain function.
The pathway is also central to the theory of aromatherapy, which proposes that volatile plant constituents inhaled through the nose can access the brain via the olfactory nerve and limbic system, allowing essential oils to influence mood, autonomic function, and neurochemistry through direct neuropharmacological mechanisms.
Inhaled menthol has shown promising effects in animal models of dementia, where repeated exposure has been reported to improve cognitive performance and reduce neuroinflammation. Recently a clinical trial found that inhalation of peppermint essential oil (containing menthol) significantly reduced the incidence of postoperative delirium, a serious complication in elderly patients following major surgery that is strongly associated with increased morbidity and mortality.
This single-centre randomised controlled trial from China enrolled 178 patients aged ≥65 years undergoing total hip or knee joint replacement, randomised 1:1 to treatment with either peppermint oil or saline. The intervention consisted of inhalation of 2 mL of a 2% peppermint essential oil solution on a cotton pad for 10 minutes, administered at three perioperative time points (night before surgery, immediately before anesthesia induction and after extubation).
The primary outcome, postoperative delirium within 3 days assessed by blinded raters using the CAM (Confusion Assessment Method) scale, occurred in 7.9 % of the peppermint group vs 19.1 % of controls (risk ratio 0.41, p = 0.048), indicating a large 60 % relative risk reduction. Secondary outcomes also favoured peppermint, with significantly lower pain scores at multiple time points, modest reductions in anxiety scores, and no increase in adverse events. However, delirium severity and duration were not changed.
The trial was only single blind, because patients could smell the peppermint, creating a substantial risk of expectancy and performance bias. However, taken together, this clinical trial (showing reduced postoperative delirium with inhaled peppermint oil) along with animal studies (demonstrating menthol-related improvements in neuroinflammation, synaptic function and memory), suggests that the brain delivery of volatile peppermint constituents via the olfactory pathway may have therapeutic relevance for cognitive disorders such as dementia. This intriguing possibility remains hypothetical and requires direct clinical testing.
For more information see: https://pubmed.ncbi.nlm.nih.gov/41390992/
