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There is a mechanism of action for aromatherapy, and a protein receptor is key

Do I “believe” in aromatherapy? Yes and no. Essential oils contain a mix of chemicals, and it makes sense that some of the chemicals will have an effect on the body. If I can have an allergic reaction to a lavender essential oil (yes, that’s unlucky), why not expect other, maybe even beneficial, effects? But I have a problem: the language used in aromatherapy, full of wishful and magical thinking, puts me off. This doesn’t exclude the possibility that some essential oils are good for you; I was waiting to see some mechanism of action uncovered by scientific research.

One of my favorite things is the smell of orange blossoms, and that’s essential oils at play. Here is some news about some essential oils, including my beloved “agua de azahar” (orange blosson water). The mechanisms of action of some chemicals present in essential oils are being elucidated. Here is an example: limonene is a chemical that smells beautiful, and it also binds to an interesting receptor, the A2A receptor, so it has to affect the body somehow. The question is, how significant is this effect?

Limonene is a major (up to 90%) aromatic compound in the essential oils extracted from citrus rind. Other orange terpenes include pinenes, myrcene, and sabinene. The application of limonene, especially in aromatherapy, has expanded. Does it work? And if yes, how?

Figure: R-limonene, a terpene present in orange essential oil


What’s adenosine? You probably know it from its presence in nucleic acids, but it has other roles. Adenosine is a nucleoside that modulates a number of physiological processes, including oxygen balance in tissues, immune response, and signaling in the nervous system. Four mammalian subtypes of adenosine receptors (ARs) have been identified, and their genes cloned, these AR subtypes are distributed in a tissue-specific manner. For example, A2A receptors are highly expressed in the brain, immune cells, heart, lung, and blood vessels. ARs differentially modulate the intracellular levels of adenosine-cyclic monophosphate (cAMP), in the case of A2A, receptor activation elevates cAMP levels.

Limonene selectively binds to the adenosine A2A receptor, which may induce sedative effects. Limonene increased cytosolic cAMP concentration and induced activation of protein kinase A and phosphorylation of cAMP-response element-binding protein; it also increases cytosolic calcium concentration.

What can you expect from limonene now that we know that it binds to the A2A receptor?

The A2A receptor

The A2A receptor, a protein, can suppress immune cells, protecting tissue from inflammation. The A2A receptor transmembrane protein binds to the signal, in this case, limonene (many chemicals can bind to this receptor), on the outside of the cell and exerts its action inside the cell. Tle ultimate result will be the activation of several target genes. 

The A2A receptor is expressed in the brain, where it has important roles in regulating glutamate and dopamine release. This makes it a potential therapeutic target for the treatment of conditions such as insomnia, pain, depression, and Parkinson’s disease. “Therapeutic target” implies the need for research in pursuit of effective remedies, which is not what quack websites want. So be aware of the dangers of fast remedies, uncluding aromatherapy.

Skin Actives products that rely on receptors

We use neroli (orange flower) water in our anti-age ant-aging hydramist, and limonene is likely to enhance the effect of strontium.

Our products containing epidermal growth factor and keratinocyte growth factor rely on the specific receptors traversing the cell membranes of cells in the skin and scalp.


Park HM, Lee JH, Yaoyao J, Jun HJ, Lee SJ. Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2A) receptors. Biochem Biophys Res Commun. 2011 Jan 7;404(1):345-8. doi: 10.1016/j.bbrc.2010.11.121. Epub 2010 Dec 4. PMID: 21134357.

Sangita Kumari, Sachin Pundhir, Piyush Priya, Ganga Jeena, Ankita Punetha, Konika Chawla, Zohra Firdos Jafaree, Subhasish Mondal, Gitanjali Yadav, EssOilDB: a database of essential oils reflecting terpene composition and variability in the plant kingdom, Database, Volume 2014, 2014, bau120,

Lakhan SE, Sheafer H, Tepper D. The Effectiveness of Aromatherapy in Reducing Pain: A Systematic Review and Meta-Analysis. Pain Res Treat. 2016;2016:8158693. doi: 10.1155/2016/8158693. Epub 2016 Dec 14. PMID: 28070420; PMCID: PMC5192342.


DISCLAIMER: These claims have not been evaluated by the FDA and are not intended to diagnose, cure, treat or prevent any disease.



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