Essential Oils, 5-HT3 Antagonists, and Mechanisms of Action for Nausea Relief

Article Revised 10/15/2023

As the market for essential oils has grown over the last decade, so has the hype. This is one reason why it’s important to separate scientific fact from marketing fiction (or at least, marketing spin). For every clinical study examining the effects of essential oils or aromatherapy, there are 10 that have little to no basis in science.

Worse, there are a number of companies that market EOs (essential oils) for purposes that aren’t just benignly ineffective, but potentially dangerous to users. While these plant extracts may be natural, they aren’t universally safe, and many certainly aren’t appropriate for ingestion, for undiluted (or even diluted!) use on skin, or on children, pregnant women, or those with certain medical conditions. This is because essential oils are chemical compounds, and like with any chemical, some are quite safe, while others require additional caution when used.

Breaking Down Essential Oils

Because essential oils are chemicals, albeit natural ones, they are comprised of constituents that can be separated into a wide variety of distinct compounds, each of which has the potential to affect living organisms, including humans. This separation is generally accomplished in a lab setting via gas chromatography–mass spectrometry (GC-MS) analysis, where the precise amount of each compound present can be broken down into percentages.

For instance, the chemical composition of Eucalyptus largiflorens can be broken down into main components of 1,8-cineole  (37.5%), p-cymene (17.4%), neo-isoverbenol (9.1%), limonene (6.5%) and spathulenol (6.7%), while those of E. spathulata oil were 1,8-cineole (72.5%),  α-pinene (12.7%) and trans-pinocarveol (3.3%), with the absence of neo-isoverbenol, limonene and spathulenol or at lower amounts (88). GC-MS reveals that monoterpenes, 1,8-cineole and α-pinene, are the main components in most species, while, E. citriodora is rich in citronellal (49.5-87%) and citronellol (8-20%) [1]. Every essential oil can be analyzed in the same detail, and studying the mechanism of action for compound individually is the only way to know with certainty which constituent causes a certain reaction or creates a specific effect.

Essential Oil Compounds as 5-HT3 Antagonists

Based on the discussion above, it should be clear that it’s not the essential oils themselves that cause a certain reaction, but the specific compounds within each oil. As it turns out, there are constituents which have been isolated and tested independently of the whole oil that are now understood to have an antagonistic effect on 5-HT3 receptors (a type of serotonin receptor). What this means is that oils that have greater proportions of these compounds can have effects similar to pharmaceutical antiemetics -- drugs that help control nausea and vomiting, especially that which is caused by postoperative conditions, chemotherapy and early pregnancy.

More than one EO contains compounds that function as 5-HT3 antagonists. One of the most well-studied is beta-Pinene (β-pinene), a monoterpene that can be found in various concentrations across multiple oils, including Lemon (6.6%); Peppermint (.55%); Ginger (.55%), and Fennel (.21%). Other compounds that have been shown to have antiemetic effects include boldine and menthol, as well as gingerol, which can be found in peppermint and ginger oils, respectively [2] [3] [4].

How Do 5-HT3 Antagonists Work?

5-HT3 receptor antagonists work by blocking the binding of the serotonin released by the GI tract due to trauma, such as chemotherapy, to the nerve receptors that transmit impulses to the vomiting center of the brain, located in the medulla oblongata. This greatly reduces the probability of a patient feeling nauseous and therefore vomiting.

While it may seem strange to think that a substance delivered via the olfactory system could affect the GI tract, scientists who have been studying this phenomenon would be much less surprised. This is because the intestines are home to many different receptors -- including those of the olfactory variety. Therefore, when a patient inhales an essential oil with 5-HT3 antagonist properties, it can help prevent nausea and vomiting, even though it isn’t processed through the digestive system.

Essential Oils: A Safe, Effective and Economical Alternative to Pharmaceutical Antiemetics

When we at Aeroscena® developed our Nausea Relief No. 44 formula for the use of patients experiencing postoperative nausea and vomiting (PONV), chemotherapy-induced nausea and vomiting (CINV), and other nausea-related discomforts, we had to go beyond what aromatherapists have historically thought to work for these conditions. Instead, we had to examine the constituents of each oil and compare them with what we know to work based on scientific research.

Personal Aromatherapy Inhalers

Once the most appropriate oils for nausea relief were selected, we looked to science again to inform our decisions regarding what would be the most effective ratio of each oil in our proprietary formula.

We also realize that science is not static or fixed. With Nausea Relief, as well as the rest of our formulas, as new research comes along, we are unafraid to experiment with both the oils used and their relative ratios. This ensures our formulas remain as effective as possible as new information becomes available.

Wearable Aromatherapy Patches

It’s clear that scientific evidence supports the use of aromatherapy as an alternative or adjunct to pharmaceutical antiemetics. When taking into consideration the number of negative side effects that these drugs can have -- headache, loss of energy, diarrhea, constipation and even neurological issues -- it is in most patients’ best interest if the medical professionals caring for them consider clinical aromatherapy as a first-line treatment for the prevention of nausea and vomiting.

Bottled Essential Oil Formulas

----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

[1] Zhang, Jinbiao & An, Min & Wu, Hanwen & Stanton, Rex & Lemerle, Deirdre. (2010). Chemistry and bioactivity of Eucalyptus essential oils. Allelopathy Journal. 25. 313-330.

[2] Heimes, Katharina & Hauk, Florian & J Verspohl, Eugen. (2010). Mode of Action of Peppermint Oil and (-)-Menthol with Respect to 5-HT3 Receptor Subtypes: Binding Studies, Cation Uptake by Receptor Channels and Contraction of Isolated Rat Ileum. Phytotherapy research: PTR. 25. 702-8. 10.1002/ptr.3316.

[3] Neurogastroenterol Motil. 2014 Jun;26(6):810-20. doi: 10.1111/nmo.12334. Epub 2014 Apr 8.
Natural compounds boldine and menthol are antagonists of human 5-HT3 receptors: implications for treating gastrointestinal disorders.
Walstab J1, Wohlfarth C, Hovius R, Schmitteckert S, Röth R, Lasitschka F, Wink M, Bönisch H, Niesler B.

[4] Neurogastroenterol Motil. 2013 May;25(5):439-47, e302. doi: 10.1111/nmo.12107. Epub 2013 Mar 12. Ginger and its pungent constituents non-competitively inhibit activation of human recombinant and native 5-HT3 receptors of enteric neurons.
Walstab J1, Krüger D, Stark T, Hofmann T, Demir IE, Ceyhan GO, Feistel B, Schemann M, Niesler B.