A study carried out by Kagoshima University researchers shows that linalool, a constituent of lavender, peppermint and many other essential oils, must be smelt — not absorbed in the lungs — to exert its calming effects, which could be used to relieve preoperative stress and anxiety disorders.
“In folk medicine, it has long been believed that odorous compounds derived from plant extracts can relieve anxiety,” said Dr. Hideki Kashiwadani, co-author of the study.
“Among them, linalool has been reported to have the anxiolytic effects.”
“Numerous studies confirm the potent relaxing effects of linalool. However, the sites of action of this compound were usually not addressed in these studies.”
“Many assumed that absorption into bloodstream via the airway led to direct effects on brain cell receptors such as GABAARs. But establishing the true mechanism of linalool’s relaxing effects is a key step in moving towards clinical use in humans.”
Dr. Kashiwadani and co-authors tested mice to see whether it is the smell of linalool — i.e. stimulation of olfactory neurons in the nose — that triggers relaxation.
“We observed the behavior of mice exposed to linalool vapor, to determine its anxiolytic effects,” they explained.
“We found that linalool odor has an anxiolytic effect in normal mice. Notably, this did not impair their movement.”
Crucially, there was no anxiolytic effect in anosmic mice — whose olfactory neurons have been destroyed — indicating that the relaxation in normal mice was triggered by olfactory signals evoked by linalool odor.
What’s more, the anxiolytic effect in normal mice disappeared when they were pretreated with flumazenil, which blocks benzodiazepine-responsive GABAA receptors.
“When combined, these results suggest that linalool does not act directly on GABAA receptors like benzodiazepines do, but must activate them via olfactory neurons in the nose in order to produce its relaxing effects,” Dr. Kashiwadani said.
“Our study also opens the possibility that relaxation seen in mice fed or injected with linalool could in fact be due to the smell of the compound emitted in their exhaled breath.”
“Similar studies are therefore needed to establish the targets, safety and efficacy of linalool administered via different routes, before a move to human trials.”
The results are published in the journal Frontiers in Behavioral Neuroscience.
Hiroki Harada et al. Linalool Odor-Induced Anxiolytic Effects in Mice. Front. Behav. Neurosci, published online October 23, 2018; doi: 10.3389/fnbeh.2018.00241