A research study led by Hajjar, Arhami, and Vaezi Kakhki investigated the effects of various plant extracts on sleep deprivation-induced anxiety in male mice. The study involved 50 mice divided into five groups, each receiving either orange blossom extract, violet extract, marjoram extract, lorazepam (a benzodiazepine sedative), or water as a control. All groups underwent 24 hours of sleep deprivation, and researchers assessed anxiety levels through three behavioral tests: the elevated plus maze, the light-dark box, and the marble burying test, alongside analyses of plasma cortisol levels.

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Results indicated that both orange blossom and marjoram extracts were more effective than lorazepam in reducing anxiety caused by sleep deprivation, with orange blossom exhibiting the highest efficacy among the tested extracts. The authors noted, "It was found that extracts of orange blossom and marjoram were more effective than the violet extract and lorazepam solution in reducing anxiety caused by sleep deprivation. Among the herbal extracts, the orange blossom extract was the most effective in this regard."

This finding is significant as it compares a plant extract with a standard pharmaceutical sedative, providing a meaningful measure of effectiveness.

The orange blossom, derived from the bitter orange tree (Citrus aurantium), contains various compounds known to affect the nervous system. Notably, linalool, a terpene in its essential oil, is recognized for its sedative and anxiolytic properties. Additionally, flavonoids in the flower help to reduce inflammation and interact with GABA receptors, similar to benzodiazepines. Other constituents include vitamin C and carotene, which are associated with calming effects.

The extraction process yields approximately one liter of essential oil from one ton of flowers, contributing to the high market price of neroli oil in perfumery and aromatherapy.

Human studies are beginning to surface. A randomized controlled trial published in PLOS One in 2024, conducted at Babol University of Medical Sciences in Iran, examined the effects of bitter orange blossom distillate syrup on 60 mothers of infants in neonatal intensive care, known for high stress-related sleep disruption. Although the improvement in anxiety scores did not achieve statistical significance, sleep quality measures showed more consistent positive outcomes.

Another clinical study reported that inhaling a 20% concentration of bitter orange extract decreased anxiety and fatigue in type 2 diabetes patients. Furthermore, postpartum women treated with orange essential oil demonstrated improved sleep quality as measured by the Pittsburgh Sleep Quality Index.

Although the evidence supporting orange blossom as an aid for sleep and anxiety is expanding, it mainly relies on animal studies and small-scale human trials. The findings from the 2019 study provide a pharmacological foundation for the traditional use of orange blossom, targeting mechanisms similar to those affected by pharmaceutical sedatives but without the risk of dependency associated with benzodiazepines. For individuals experiencing mild sleep disruptions linked to anxiety, orange blossom appears to be a low-risk complementary option, but it should not substitute clinical treatment for chronic insomnia or anxiety disorders.