The relaxation effect of EOs is due to their effect on neuroreceptors and electroencephalographic rhythms – a study finds

Significance 

Essential oils (EOs) are concentrated hydrophobic liquids containing volatile aroma compounds which are extracted from herbs, flowers, and other plant parts. Essential oils and the constituents in them exhibit different pharmacological activities, such as antinociceptive, anxiolytic-like, and anticonvulsant effects. They are widely applied as a complementary therapy for people with anxiety, depression, insomnia, convulsion, pain, and cognitive deficit symptoms through inhalation, and aromatherapy. Not only that, but some studies also suggest that they may help alter the course of neurodegenerative disorders like Alzheimer’s. Researchers think these effects are possible due to their impact on neurotransmitters and resulting changes in brain wave activity. Despite the popularity of EOs as a safe way to manage certain health conditions, unlike pharmacological drugs, little is known about their mechanism of action,.

A lot is known about how neurotransmitters work, their role in the movement, cognition, pain, reward, and addiction. In addition, it is known that dysregulation of neurotransmitters may particularly lead to different psychiatric conditions. Since neurobiologists gained a lot of knowledge on the role of neurotransmitters in different psychiatric disorders, they have developed drugs to modulate their brain levels. There are many drugs that can help in psychiatric conditions and different brain disorders. Their mechanism of action is via modulating the binding of neurotransmitters to various receptors. Similarly, from early studies, researchers know how modulating the impact of multiple neurotransmitters may change brain waves, as visible on electroencephalography (EEG). It means that EEG changes may also suggest what neurotransmitter pathways are modulated by any substance.

In this study, Australian researchers: PhD candidate Minoli Aponso, Milton Hearn, Antonio Patti and led by Professor Louise Bennett from the School of Chemistry at Monash University studied the relative neurotransmitter receptor binding efficacy of a large number of EOs and reference compounds. They calculated the neurotransmitter-receptors binding affinity of 9 EOs and 7 different neurotransmitters using molecular docking experiments. Additionally, they studied the changes in the EEG caused by EO by referring to studies done earlier. Among the neurotransmitters, they studied excitatory noradrenaline, glutamate, serotonin, and acetylcholine, and inhibitory glycine, GABA, and dopamine. Reference compounds were melatonin, venlafaxine, piracetam, propofol, and other well-known compounds. Among the EOs they studied were alpha-pinene, linalool, rosemary, Mentha arvensis, cannabis, lavender.

The authors had several interesting findings. For example, computer models showed that neurotransmitters had a high affinity for their native receptors, but they also had a weak affinity for other receptors. On the contrary, reference compounds had a strong binding affinity to specific neurotransmitter receptors. In comparison to reference compounds and neurotransmitters, EOs showed weak and partial agonist interaction that mimicked the pattern of the native ligands to the inhibitory glycine-a-GLRA3 and dopamine-D2 receptors. This pattern of interaction was weaker but relatively closer to piracetam and propofol, showing that their interaction was in the subtherapeutic range.

Furthermore, when the research team compared the effects of different EOs (the same set that were analysed by molecular docking) on EEG responses with reference compounds, they found EOs mainly affected the dynamic range of EEG-alpha, with some effect on theta and beta brain rhythms. In contrast, reference compounds had a more significant influence on EEG-delta and suppressed alpha and theta brain waves. This ability of EOs to influence alpha rhythms appears to indicate their ability to regulate cholinergic and monoaminergic pathways. Additionally, researchers also showed that EOs could cause a rapid onset effect on brain waves, potentially reflecting modulation of the levels of neurotransmitters themselves. Therefore, their action may regulate brain waves by this pathway rather than their direct impact on neurotransmitter receptors.

To conclude, the new study by Professor Louise Bennett and her research team is among the first to ever evaluate the mechanism of action of a commonly used EOs. This may help improve EO-based treatment approaches for various brain disorders, especially for managing mood disorders. Moreover, better understanding of the mechanism of action of EOs will help in designing better pharmacophores during new drug development to control a variety of brain disorders including pain and anxiety.

In a statement to Medicine Innovates Professor Bennett said: “There is enormous potential for elevating Essential oils into proven therapeutics. We need to take advantage of their ease of bioavailability to the brain and dose control, simply by controlling the period of inhalation. However, we also need to understand the mechanisms of their biological effects, so efficacy can be optimized.”

About the author

Dr Minoli Aponso, completed undergraduate studies in Food Science & Technology at University of Sri Jayewardenepura, Sri Lanka (2016), and recently her PhD at Monash University (2022), on the topic of ‘Understanding physicochemical properties of Essential oils relevant to intake by inhalation for optimizing neuropsychological efficacy’. As phytochemicals in food play a major role in human health, Essential oils too hold an amazing potential ability to treat brain disorders under proper administration. Having a passion to help people to live healthy lives, Dr Aponso seeks to discover and understand the chemistry behind inhaled Essential oils to optimize how they can be effective for psychological and cognitive therapies. Dr Aponso has expertise across the disciplines of food chemistry, phytochemistry, biochemistry and analytical chemistry and is comfortable working across these disciplines with aspiration to support the translation of research innovation.

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About the author

Emeritus Professor Milton Hearn AM, FTSE, FAICD, FRACI CChem, FRSV, FIUPAC, FIChemE(A), FRSC, is an internationally recognised chemist, well known for his pioneering studies in chemistry, biotechnological sciences and engineering, and their practical translation to industrial applications, resulting in several major developments in therapeutic drug design, manufacture, and analysis. Professor Hearn completed his PhD (1970) and DSc (1983) at The University of Adelaide. He has received numerous prestigious national and international awards, including the RACI Leighton Medal, the ACS Chromatography Award and the ACS Alan Michaels Award. During his career, his creative scientific work has resulted in >690 original peer-reviewed publications and multiple patents and invention disclosures. Professor Hearn was appointed Professor of Chemistry at Monash University in 2002 (previously Professor of Biochemistry in 1986) and from 2003, Director, Monash Centre for Green Chemistry. This international centre of multidisciplinary research excellence focuses green and sustainable chemistry concepts and methods with novel technologies adopted by the chemical, pharmaceutical, biotechnology and life science industries.

About the author

Professor Tony Patti is based at the Monash University School of Chemistry. Professor Patti completed his PhD at the University of Melbourne (1979). After a short period in industry (Glaxo), he moved to academia. His research expertise is in organic chemistry in relation to valorisation of organic materials from food and agricultural discards (waste), soil chemistry and green chemistry. He is currently the course Director for the Master of Green and Sustainable Technologies, a postgraduate program focusing on green chemistry. He is also Director of the ARC – Industrial Transformation Training Centre – Green Chemistry in Manufacturing. Tony has co-authored >140 publications and industry reports and has contributed to 3 patents as a co-inventor.

About the author

Professor Louise Bennett completed undergraduate and post-graduate studies (University of Melbourne, 1985) before PhD (Monash University, 1997) and post-doctoral studies (Peter Macallum Cancer Institute, 1997). After 20 years at CSIRO in Agriculture and Food business units, Louise was appointed Professor of Food Chemistry at Monash University in 2017. Louise is a trans-disciplinary scientist working across food science and clinical research and its translation into knowledge and useful products that advance the supply of food, and its efficacy for human and animal health. At Monash University, Louise is the course Director of the Master of Food Science and Agribusiness, and Co-director of Monash Food Innovation. Louise has authored >80 publications and is a co-inventor of 1 patent.

Reference

Aponso, M., Hearn, M. T. W., Patti, A. F., & Bennett, L. E. (2022). Relaxation Effects of Essential Oils Are Explained by Their Interactions with Human Brain Neurotransmitter Receptors and Electroencephalography Rhythms. ACS Chemical Neuroscience, 13(1), 166–176. https://doi.org/10.1021/acschemneuro.1c00731

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