Traditional medicine has long used aromatic herbal compounds such as lavender extract to treat anxiety, but how these compounds function at the neuronal level is not fully understood. A team of scientists in Japan has now shown that the smell of the aromatic lavender-derived alcohol linalool exerts anxiolytic effects in mice by acting on the same gamma-aminobutyric acid A receptors (GABA A Rs ) respond to the anxiolytic drug benzodiazepam. While diazepam in the blood acts directly on GABA A receptors, the team at Kagoshima University found that linalool vapor acts on the animals' olfactory system ̵
Hideki Kashiwadani researchers from Kagoshima University suggest further studies will be needed to further investigate the target, effects, and potential side effects of linalool. The compound could be conveniently used to reduce anxiety To reduce patients in the clinical setting. "These findings, however, bring us closer to the clinical use of linalool in relieving anxiety, for example, in operations where pretreatment with anxiolytics relieves preoperative stress and can help to place patients more smoothly in general anesthesia. Kashiwadani. "The vaporized linalool could also be a safe alternative for patients who have difficulties with oral or suppository administration of anxiolytics, such as infants or confused elders."
The results of the team are reported in Frontiers in Behavioral Neuroscience . in an article entitled "Linalool odor-induced anxiolytic effects in mice."
Anxiety disorders are one of the most common types of mental disorders, the authors write. First-line drug therapies include azapirone and serotonin-selective reuptake inhibitors (SSRIs), which act on serotonergic synaptic transmission, along with benzodiazepines that act via GABAergic transmission, but the side effects of these drugs may be worse than the anxiety itself.  Plant-derived aromatic compounds, including lavender extract, have been used in folk remedies for many years for the treatment of anxiety. "The neural mechanisms that have the reported anxiolytic effects of th The odors are not yet fully revealed," notes the team. Previously, several studies have investigated that linalool inhalation-induced anxiolytic effects occur. However, since the contribution of the olfactory system was not directly investigated, the way in which linalool can induce the effects has not been revealed.
Researchers now report studies that included performing classical anxiety tests on male mice after exposure to linalool vapor, and the results of the Hell / Dark Box test and increased plus maze tests suggested that linalool vapor exposure produced dose-related anxiolytic effects comparable in some cases to those produced by diazepam treatment, but unlike benzodiazepam or linalool injections, exposure to linalool odor did not result in motor disturbances, and the test results suggested that the effect of the linalool odor was anxiolytic rather than sedative.
Significantly, linalool vapor was only effective in mice that had a sense of smell. * Exposure to linalool vapors had anxiolytic effects in anosmic mice have been pretreated with a compound that their olfactory Rez Eptors destroyed. Similarly, animals pretreated with a compound flumazenil that blocks the benzodiazepine site on GABA A Rs did not respond to linalool vapor, "indicating that GABAergic transmission via benzodiazepine-dependent GABA A Rs was essential for anxiolytic effects, "explain the authors. "Taken together, these results suggest that linalool does not act directly on GABA receptors, such as benzodiazepines, but must activate them via olfactory neurons in the nose to exert its relaxing effects," notes Dr. Kashiwadani
Interestingly, previous studies have shown that other odors, including (+) – limonene found in citrus peel, also have anxiolytic effects when inhaled. However, in the case of (+) – limonene, pretreatment with flumazenil does not block its relaxing effect. Together with our findings, it is possible that there may be at least two parallel anxiolytic pathways involving benzodiazepine-responsive GABA A Rs-dependent and independent systems, which are caused by odor input.
Prior Research has found that systemic administration of linalool by intraperitoneal injection also induces anxiolytic effects, suggesting that inhaled linalool acts via glutamatergic neurotransmission after it enters the bloodstream via the airways. Dr. Kashiwadani suggests, "Our study opens the possibility that relaxation in linalool-fed or injected mice could actually be due to the smell of the compound expelled in their exhaled breath."
"These results provide information about the possible central neuronal mechanisms, Effects and foundations for the investigation of the clinical application of linalool – odors in the treatment of anxiety ", say the authors write. "Linalool odor-induced anxiolytic effects may be applicable to preoperative patients, as pretreatment with anxiolytics may alleviate preoperative stress and thus help to place patients more smoothly under general anesthesia." For patients experiencing difficulties with oral or suppository administration of anxiolytics, such as Infants, the use of linalool odor to reduce anxiety may be a suitable and promising alternative. "