If you’re reading this, you most likely use essential oils. You know your antimicrobial, anxiolytic and anti-inflammatory oils, and probably diffuse your comfort oils to bright up the mood. You might also have some overview of the chemistry of essential oils and how to use them safely.
But have you ever wondered how essential oils work? How they can affect both the body and the mind, and are there different mechanisms at work? Is it important to understand how they work in the first place?
That depends, of course, on how you’re involved in aromatherapy. Understanding the principles of how essential oils work can undoubtedly give you a more in-depth perspective on the ways you can use them. On another note, it enables you to safely bypass nonsensical ideas, such as the functional group approach which only imbues aromatherapy with unnecessary confusion.
Throughout the major part of its history, aromatherapy has been based on the traditional use of aromatic plants. In the second half of the 19th century, empirical research on essential oils took place. Biological properties and chemistry of essential oils began to be studied more systematically. In the 1890s, pinene, limonene and terpinolene were among the first chemically characterised terpenes (Kubeczka 2016).
By the time René-Maurice Gattefossé entered the scene, major constituents were known – Gattefossé mentions over 40 in his book Aromatherapy (1937/1993) – along with their structure, or at least molecular formula. Knowledge of the biological properties of essential oils in that time was a mix of herbal medicine, individual case reports and early experiments.
In subsequent decades, more sophisticated experimental methods were developed: various in vitro assays and animal models for testing biological effects in vivo. However, despite the accumulating knowledge what essential oils do, nothing was known about how they work.
It was not until the late 1980s when pharmacodynamic research on the constituents of essential oils started to emerge, focussing on molecular mechanisms. Of those early studies, some of the more salient were elucidation of the mechanism for the spasmolytic activity of menthol and peppermint oil (Hawthorn et al 1988) and the finding of a connection between linalool and glutamatergic system (Elisabetsky et al 1995), which explains an integral part of how lavender or other linalool-rich oils exert their generally calming effect.
Indeed, it took roughly a century from the early days of elucidating the molecular structure of the first constituents to the beginnings of unravelling the mysteries of their biological activity.
Currently, in times when the discovery of new synthetic drugs has been declining, we’re witnessing an explosion of natural products research, of which plant volatiles and essential oils play a significant role.
So, how do essential oils work? It has become widely accepted that they can act via pharmacological and psychological mechanisms. These are the two fundamental mechanisms, as they are mediated respectively by the body and the mind. We’ll look separately into each, although in practice they often overlap and interact (which is a good thing!), and it may be difficult to distinguish between them. Note that this is not a “this oil does this and that oil does that” type of article but more like a bird’s eye overview.
Effects of essential oils on the body are usually termed pharmacological because they are subject to pharmacokinetic parameters of absorption, distribution, metabolism and elimination. Pharmacokinetic parameters determine bioavailability and affect the toxicity of constituents.
Bioavailability is the crucial pharmacological parameter, and it must be sufficient to produce observable pharmacological effects. If you take a few whiffs of essential oil from the bottle, the concentration of bioactive constituents in your blood will be too low to reach pharmacologically relevant levels. However, the issue of bioavailability is complex, and it will be addressed in another post. Here, we’re only concerned with the general principles.
If there’s one thing you should know to understand the difference between pharmacological and psychological mechanism, it’s substance specificity. Pharmacological effects are substance-specific, which means that a given constituent will cause similar effects (yet not necessarily to the same degree) across the different subjects, by acting on the same molecular targets in a dose-dependent manner.
After entering the body via inhalation, topical application or internally, the constituents can bind to various proteins, such as ion channels, receptors, enzymes, carrier proteins, and proteins involved in signalling pathways. Due to their lipophilic nature, most can readily dissolve in cell membranes, where they can disrupt communication of the cell with its surrounding. Many antimicrobial constituents work by disrupting the cell membranes of microbial pathogens. The same thing happens in the cell membranes of our tissues, which is why potent antimicrobial oils are also potential irritants.
Essential oil constituents typically exert their pharmacological effects by inhibiting the function of the proteins they bind to, and therefore inhibit or slow down associated biological processes. That is how lavender can induce calming and sedative effects in the brain, or how anti-inflammatory and spasmolytic effects are mediated.
Approximate size comparison between (A) cyclic monoterpene, (B) mid-sized protein and (C) phospholipid bilayer of a cell membrane. It seems quite hard to imagine how a tiny molecule 500th or 1000th the mass of a protein can modify its functional properties, right?
In some cases, the constituents activate specific receptors and consequently enable or speed up associated processes. That is how many anxiolytics work, or why peppermint oil feels cold, or how we’re able to sense the smell of essential oils.
So far that might not sound very fascinating. But that’s how all pharmacologically active substances work, regardless of whether they’re of natural or synthetic origin. They either activate some process in the body or deactivate it. They don’t remove the cause for the condition but help the body to better cope with an out-of-balance situation, and – ideally – heal on its own.
There’s no magic panacea like the ancient Mithridatium that could protect us from every disease. I know no-one wants to hear this, but the paradox of life is that organisms inevitably sentence themselves to death by the very source they’re crucially dependent on: oxygen. All higher life forms need oxygen to be able to maintain their highly efficient metabolism. But that same efficient metabolism produces free radicals from the oxygen, which slowly, but inevitably cause our cells and bodies to ‘rust’ over the years. This is the fundamental cause for ageing, and there’s no way around it – despite the ingenious biochemical mechanisms that have evolved to slow it down, and all the antioxidants and healthy lifestyles.
Unfortunately, no medicine can provide some utterly new functionality to the body that previously wasn’t there; what they can do is help re-establish the balance to physiological processes that for whatever reason went out of ‘focus’.
ESSENTIAL OILS AND THE IMMUNE SYSTEM
Take the immune system. A healthy immune system is precisely tuned to distinguish between pathogenic substances and the body’s healthy tissue. When this balance is lost, an overactive immune system starts invading its own body, which can result in chronic inflammation and autoimmune diseases. When the immune system is weak on the other hand, we succumb to microbial infections.
Immunostimulation works on the immune system and antimicrobial activity directly inhibits the growth of microorganisms, hence these are two different biological activities.
These are the two sides of the same coin, as common molecular mechanisms are involved. Anti-inflammatory substances suppress the immune system and damage repair system, and immunostimulants act pro-inflammatory, they stimulate inflammation.
The immune system is undoubtedly susceptible to poor diet, for example to deficiencies of protein, zinc or vitamin D, and can be improved accordingly. But evidence that small organic compounds of plant origin can specifically fortify a normally functioning immune system is weak (Gertsch et al. 2011, Anastasiou and Buchbauer 2017).
The claims that essential oils can ‘boost’ the immune system thus seem to be premature, as they are clearly taken out of the in vitro context. With sufficient concentrations of bioactive constituents – commonly exceeding in vivo bioavailability or tolerability by a factor of 1000 – it’s not difficult to show an immunostimulatory response of cultured immune cells or even changes in their gene expression. However, as immune processes are complex and mediated by interactions between different tissues and cell types, they can only be unambiguously studied in vivo (Gertsch et al. 2011).
MIXTURE MAKES THE DRUG: SYNERGY AND NETWORK PHARMACOLOGY
Nonetheless, there are more exciting things about essential oils. As small and highly diffusive molecules, terpenes and other essential oil constituents seem to be almost designed, and likely have evolved, to reach maximum diversity and number of potential targets. That’s beneficial for the multi-purpose defence and communication systems of plants.
Instead of a small number of highly potent products, plant evolution seems to have favoured diversity (Firn and Jones 2003), which is particularly evident in the case of aromatic plants and plant volatiles. Not only can a single constituent bind to a variety of proteins, but mixtures of constituents can affect multiple networks of molecular processes, if sufficiently bioavailable.
Biological processes can be thought of as interrelated networks. Affecting multiple nodes at the same time can have a more robust effect on the system as a whole.
Thinking in terms of network and systems pharmacology opens up a vast space for the potential synergistic effects. By targeting networks instead of single molecules, synergistic interactions can affect pharmacokinetics (increasing bioavailability), or increase the robustness of pharmacological effects. By utilising mixtures of constituents, a similar effect can be achieved with pharmacologically less potent substances, reducing potential side effects encountered with conventional medicines that are based on highly potent monosubstances (Gertsch 2011).
Network effects and synergistic interactions can theoretically occur in a variety of possible ways. However, they should be applied in a therapeutic context very carefully, as more parameters come into play that need to be taken into account. We are only beginning to probe this immensely complex space. But as Jürg Gertsch (2011) remarks, to achieve such level of depth in pharmacognosy, the molecular mechanisms need to be understood first. And I may add, we seem to be well under way.
To be clear, biological activities thus far discussed are not specific to essential oils. Flavonoids, for example, also show great structural diversity and a range of biological actions such as anti-inflammatory, antimicrobial, antioxidant, anxiolytic, neuroprotective etc., and can act on multiple targets as well. Is there anything special about essential oils, after all?
Well, yes. The small size of essential oil constituents enables them to diffuse into the air, and we can smell them. By definition, we cannot smell any plant products other than the volatiles.
Our ability to consciously or subconsciously perceive odours opens up entirely new territory for understanding how essential oils work. In contrast to pharmacological mechanisms, psychological effects are not substance specific: they don’t depend on the plasma concentration of the constituents, their binding affinity to target proteins, and other pharmacological parameters. They depend on the context of odour presentation: our memories and the current state of mind. Thus, when it comes to smell, it becomes more difficult to establish general relations in a sense “X oil has Y effect”, as psychological effects are very subjective.
HOW DOES THE PSYCHOLOGICAL MECHANISM WORK?
Psychological effects emerge from the cognitive processes initiated in the olfactory system and mediated through neuronal excitability – the ability of neurons to generate and conduct electrical signals.
Once an odorant binds to olfactory receptors, the chemical signal is transduced into a neural signal in the form of action potentials, tiny electrical currents that propagate along neurons. These are further encoded into large-scale synchronous patterns of neuronal oscillations that are communicated across the different parts of the brain and integrated into a holistic interpretation of the odorant. It’s at this stage that we consciously experience odours and assign meaning to them. The conscious experience initiated by odorants feeds back on the neurophysiological processes to modulate our mood, cognition, physiological arousal and behaviour.
Olfaction is pretty unique compared to other sensory modalities. One distinct neurological feature of olfaction is a rather direct connection of the olfactory tract with brain structures specifically involved in emotion, memory and associative learning. Such a targeted connection could help explain some peculiar properties of olfaction, such as its strong association with memories and emotions. On the other hand, some other neurological features make smell perception strongly susceptible to modulation with higher cognitive processes, such as beliefs and expectations.
Perhaps contrary to popular belief, limbic system does not seem to play the key role for the psychological effects of smells in humans. In fact, there is no universal agreement as to which structures of the brain belong to the limbic system, and whether it comprises an integrative functional unit. Although limbic structures (most notably, amygdala and hippocampus) play an important role in the early stages of olfactory processing, recent research suggests that piriform and orbitofrontal cortex are major associative structures for the conscious experience of smells, their emotional and behavioural relevance, and integration with other sensory modalities (Seubert et al. 2017).
In an influential article, Joseph Stephan Jellinek (1997) described three different psychological mechanisms how smell perception could affect mood, cognition, physiology and behaviour, which remain widely referenced in the research:
1. Via the hedonic valence of smell perception. Odour valence – its pleasantness or unpleasantness – is the most salient perceptual property of smell. Odours with distinct hedonic value, either positive or negative, can have an immediate effect on our mood and physiological arousal, as well as can indirectly influence our behaviour. For example, pleasant smells can help reduce emotional tension (or simply cheer you up), amplify social interaction and increase work efficiency, and unpleasant smells can lower tolerance for frustration (Baron 1990, 1997, Baron and Bronfen 1994, Knasko 1992, Rotton 1983, Weber and Heuberger 2008).
However, a variety of factors affect the value of perceived odour: familiarity with an odour, differences in culture, genetics and individual experience, metabolic and emotional status, and beliefs about the odour.
2. By invoking context-dependent memories through associative learning and recall (in Jellinek’s terminology this is known as the semantic mechanism; however, this term may cause confusion with other effects). Here, odours serve as contextual cues for the retrieval of associations and memories of events that were associated with them in the past, and they can affect our mood and behaviour consciously as well as at the subconscious level.
Odour-evoked memories were shown to be more emotional and evocative than memories evoked by other sensory cues, and this is especially the case in autobiographical memories (a.k.a. the Proust effect). Therapeutically, odour-evoked memories can be exploited for enhancing the mood and feelings of love and support (such as in comfort smelling), to tame cravings, and for enhancing nostalgia and associated feelings of social connectedness, optimism and self-esteem (Herz 2016).
3. Through expectancy of suggested effects (the placebo mechanism in Jellinek’s terminology). Here, effects are caused or modified according to prior beliefs and expectation regarding the odour. If you believe or are led to believe you’re smelling a ripe banana, you’ll evaluate the smell of the same odorant (isoamyl acetate in this case) as significantly more pleasant than when you think it’s a paint thinner (Djordjevic et al. 2008).
Something similar happens when you believe an oil you’re smelling will enhance your cognitive performance (Moss et al. 2006) or is harmful to your health (Dalton 1999). Your cognitive performance can actually increase, and you can viscerally start feeling bad, but this happens because you tricked your own mind into believing what you were told. Placebo effect (and related concepts of autosuggestion and emotional self-regulation) is a very powerful mechanism that should not be underestimated (Beauregard 2007), and it can be your friend or enemy.
How can we make sense of the different mechanisms discussed? Clearly, the mode of action will depend on the mode of application, but we can expect at least some interaction between different mechanisms – and here’s where it gets interesting.
For example, psychotherapeutic effects of essential oils can be mediated by both pharmacological and psychological mechanism. Linalool can work on the central nervous system through the pharmacological mechanism – by acting on specific ion channels and receptors – but it can also act through pleasantness, associations and expectations associated with its smell perception.
In a therapeutic context, smelling lavender can induce a calming effect through the expectancy of the calming effect itself, if such an experience has been previously associated with the smell of lavender. The calming effect can then be further consolidated by the inhibitory polypharmacological action of linalool on glutamate receptors and voltage-gated sodium channels, if sufficiently bioavailable. However, if you find the smell of lavender repulsive, or it reminds you of some bad experience in your life, it may rather act oppositely and make you frustrated.
In many cases, the mechanism behind an observed effect is not clear and further research is needed. But it’s the interactions between different modes of action that add a little bit of art to the science behind how essential oils work, making aromatherapy such a fascinating, yet often misunderstood discipline. We’ll go deeper into this subject in the next post!
I would like to thank Matej Plankar PhD for help. This article is dedicated to Mimi. May she rest in peace.
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Photos: Pixabay; featured photo by Michael W. Davidson, Florida State University via Flickr.