Traditional medicine has long used aromatic plant-derived compounds such as lavender extract as treatments for anxiety, but how these compounds could work at the neuronal level is not fully understood. A team of scientists in Japan has now demonstrated that the fragrance of the aromatic lavender-derived alcohol, linalool, exerts anxiolytic effects in mice by acting on the same gamma-aminobutyric acid A receptors (GABA)ARs) that respond to the anxiolytic drug benzodiazepam. Diazepam in the bloodstream, however, works directly on GABAA receptors found the team of Kagoshima University that linalool-vapor worked through the olfactory system of the animals; the relaxing effects were not evident in mice that could not smell.
The researchers, led by Hideki Kashiwadani, Ph.D., from Kagoshima University, suggest that although further studies are needed to evaluate the purpose, effects and possible side effects of linalool more thoroughly, the new findings indicate that the compound might be used to reduce the anxiety of patients in clinical settings. "Nonetheless, these findings bring us closer to clinical use of linalool, for example, to relieve anxiety in operations, where pretreatment with anxiolytics can alleviate preoperative stress and thus help to place patients more smoothly under general anesthesia," notes Dr. Kashiwadani on. "Evaporated linalool could also provide a safe alternative for patients who have problems with oral or suppository administration of anxiolytics, such as infants or confused elders."
The team's findings are reported in Limits in Behavioral neuroscience, in a paper with the title: Linalool odor-induced anxiolytic effects in mice.
Anxiety disorders are one of the most common forms of mental disorders, the authors write. First-line drug therapies include azapirons and serotonin-selective reuptake inhibitors (SSRIs) that act on serotonergic synaptic transmission, along with benzodiazepines that act via GABAergic transmission. However, the team notes that the side effects of these drugs may be worse than the anxiety itself.
Plant aromatic compounds, including lavender extract, have been used in folk medicine for many years to treat anxiety. "However, the neuronal mechanisms that underlie the reported anxiolytic effects of the fragrant compounds have not yet been fully disclosed," the team states. "Previously, several studies have investigated that inhaled inhalation caused by linalool caused anxiolytic effects, but because the contribution of the olfactory system was not directly investigated, the nature of how linalool can cause the effects is not revealed."
The researchers are now reporting on studies that involve conducting classical tests for anxiety on male mice immediately after the animals have been exposed to linalool vapor. Results from the light / dark chest test and the elevated plus-maze test suggested that linalool exposure to vapor caused dose-related anxiolytic effects that were in some cases similar to those caused by diazepam treatment. However, in contrast to benzodiazepam or linalool injections, linalool odor exposure did not cause motor impairment and the test results suggested that the effects of linalool odor were anxiolytic rather than sedative.
It is significant that linalool vapor only has an effect in mice with a sense of smell. Exposure to linalool vapor had anxiolytic effects in anosmic mice. These animals had been pre-treated with a compound that destroyed their olfactory receptors. Similarly, animals pretreated with a compound flumazenil, which blocks the benzodiazepine site on GABAARs also did not respond to the linalool vapor ", indicating that GABAergic transmission via benzodiazepine-responsive GABAARs was essential for anxiolytic effects, "the authors state." In combination, these results suggest that Linalool does not work directly on GABAA receptors such as benzodiazepines do – but need to activate them via olfactory neurons in the nose to produce the relaxing effects, "notes Dr. Kashiwadani.
Interestingly, previous studies have shown that other odors, including (+) – limonene – found in the peel of citrus fruits – also have anxiolytic effects when inhaled. However, in the case of (+) – limonene, pretreatment with flumazenil does not block its relaxing effects. "Along with our results, it is possible that there are at least two parallel anxiolytic pathways involving benzodiazepine-responsive GABAARs dependent and independent systems evoked by olfactory input. "
Prior research had found that administration of linalool systemically by intraperitoneal injection also induced anxiolytic effects, leading to the assumption that inhaled linalool works via glutamatergic neurotransmission after it reaches the bloodstream through airway absorption. Dr. However, Kashiwadani suggests: "Our study opens the possibility that relaxation in mice fed or injected with linalool may in fact be due to the smell of the substance emitted in their exhaled breath."
"These results provide information on the possible central neuronal mechanisms underlying the olfactory-induced anxiolytic effects and the basis for investigating the clinical application of linalool odor in anxiety treatments," the authors write. "Linalool odor-induced anxiolytic effects may apply to pre-operative patients because pretreatment with anxiolytics may alleviate pre-operative stress and thus contribute to smoothering patients under general anesthesia.For patients who may have problems with the oral or suppository administration of anxiolytics, such as infants, can also be used as a convenient and promising alternative using linalool odor to reduce anxiety. "