Beyond the Amygdala: Decoding the Four Mechanisms of Functional Scent

There is no sense more peculiar and more fascinating than the sense of smell. We are already deeply familiar with its connection to emotion, yet few of us consider the neural and physiological architectures that create this link and how these very features could be employed in the question of functional and emotion/mood-modulating fragrances.

In this article, I would like to show the complexity and the different ways a scent canAlina Rosu, perfumer and founder, NEUNÉRECourtesy of Alina Rosu influence how we feel and act. I will start by explaining arguably the most popularized mechanism, the emotional loop. But we also need to consider the trigeminal effects, the bioavailability, and finally, the psychological effects of expectation.

The sense of smell is unique among the senses because of the way its signals are transmitted and the neural pathways they follow. Unlike vision or hearing, olfactory information bypasses the thalamus, one of the most important areas in the brain responsible for conscious perception. The thalamus typically decides which information will be processed and which will not²¹. However, in the case of olfaction, sensory input travels almost freely to brain regions involved in memory, emotion and behaviour. We often say that a scent goes directly to the “brain” or to the amygdala, but allow me to trouble you with a bit more detail.

From the moment a molecule binds to an olfactory receptor, it takes only a couple of synapses for the signal to reach the limbic structures. While the amygdala is the most cited destination, it is just one of several regions, and this is a crucial detail, as the signal engages a much broader network.

That said, the direct connection to the amygdala remains critical. This structure acts as a central hub for encoding emotions and emotional responses. This means that odors we have encountered before will always have a valence; they will not be neutral, but instead will be associated with the emotional experience that accompanied the smell⁴. 

Moreover, when we encounter the scent again, there is no decision about whether to trigger the associated emotional response or not, because we do not have a gatekeeper like the thalamus to regulate it. Odor-emotion interaction happens automatically and involuntarily, and this characteristic may be key to modulating emotions and mood.

From the amygdala, the signal is then projected to the hypothalamus¹⁹, and here is where things get physiological. Through its regulation of hormones, the hypothalamus produces chemical changes in the body, and this mechanism is central to how it shapes desire, mood, behavior, motivated action and stress responses¹⁶. 

Olfactory stimulation can modulate hypothalamic activity and, in turn, our internal physiology related to stress²². Certain odors can induce stress⁸while others can reduce it⁶. Several studies have demonstrated physiological changes associated with reduced stress biomarkers, such as decreases in salivary cortisol and chromogranin-A, following exposure to certain odors. For example, the smell of rose oil or the aroma of black tea has been shown to lower stress levels¹⁵.

But this is still not the whole story. Within our nose, we actually rely on two distinct systems for chemical detection. Besides the emotional mechanism of the olfactory system, we also possess a trigeminal system³.

While the olfactory system allows us to “smell” a scent, the trigeminal system allows us to “feel” it. Originally evolved to detect potential threats like smoke or ammonia, the trigeminal system plays a significant role in regulating arousal, alertness and attention. Because it functions as an automatic safety mechanism, it engages the body’s involuntary control center in a way that pure smell does not⁹. Consequently, its stimulation can produce rapid physiological effects like increased heart rate, respiration changes, skin conductance, and very specific P300 brain waves associated with focus and decision making.

While the olfactory system allows us to “smell” a scent, the trigeminal system allows us to “feel” it.oksanatukane at Adobe Stock

Unlike olfactive preferences, trigeminal sensation doesn't require social learning or semantic conditioning to produce basic responses. Because these reactions are innate rather than learned, the research data on the topic is remarkably consistent, making the functional effects of this stimulation far less subjective and more replicable than those of pure smell.

Research has identified specific molecules to stimulate the trigeminal nerve and elicit functional effects. A landmark example is menthol from peppermint oil, found to be stimulatory and able to increase alertness and memory speed¹⁷. Similarly, cinnamaldehyde from cinnamon oil can significantly decrease fatigue while increasing alertness²⁰.

Eucalyptol, found in eucalyptus or rosemary oils, however, presents a more complex physiological profile. While it acts as a mild trigeminal irritant, evidence suggests its primary effects on cognitive performance may come from its direct absorption into the bloodstream¹⁸. 

This brings us to the third mechanism of how fragrances can influence us. While we still perceive their scent, some molecules have the ability to cross from the lungs to the blood, and even the blood-brain barrier, effectively acting as pharmacological agents.

A prime example of a molecule acting as a systemic drug is linalool, present in lavender, coriander seeds and rosewood oils. Once it crosses the blood-brain barrier, it has antidepressant-like, mild sedative and anxiety-reduction effects coming from its interaction with serotonin pathways⁷. The strongest proof that linalool acts as a therapeutic agent in humans comes from studies on Silexan, a standardized lavender oil preparation used as an oral anti-anxiety medication.

Two other notable molecules are the alpha- and beta-pinene. Researchers wanted to scientifically isolate the impact of the scent component from the visual and physical sensations of the forest bathing practice. To do this, subjects were exposed to vaporized hinoki oil, consisting mainly of alpha- and beta-pinenes, in a controlled hotel room environment. The analysis of urinary biomarkers revealed a significant reduction in stress hormones like adrenaline and noradrenaline as well as a simultaneous boost in immunity cells¹³. 

Linalool, found in lavender, has anxiety-reduction and mild sedative effects. New Africa at Adobe StockIn contrast, (R)-limonene delivers a dual effect with a sharp trigeminal activation for immediate alertness¹⁰, followed by a pharmacological activity where it interacts with neurotransmitters to boost dopamine and create a motivating and mood-lifting effect⁵. Given its high abundance and safety profile, (R)-limonene is considered a favorable candidate for development as a nutraceutical to help with anxiety, but also curb the onset of neurodegenerative diseases like epilepsy or multiple sclerosis.

However, the emotional loops and biology are not the only drivers. To fully understand how scent affects us, we must look at a fourth mechanism, the power of cognitive expectancy. It is the way our beliefs about a scent changes how it affects our body. 

A revealing study¹ explored how our beliefs modulate our physical reaction to odors. The researchers used lemon oil, which typically triggers physiological arousal and alertness as mentioned previously, and a strawberry scent, which is considered relaxing. They then told participants that the lemon oil was relaxing, instead of the truth that it is actually stimulating. As an effect, the physiological arousal usually caused by lemon was significantly lower. 

Another study¹⁴ found that when participants were exposed to heat pain while smelling lavender oil, those who were explicitly told that lavender oil relieves pain showed significantly lower pain ratings and stress markers compared to those told it was a neutral odor. Although the chemistry remained constant, the cognitive expectancy significantly boosted the analgesic outcome. This confirms that our brain's expectation has the power to inhibit or amplify the effects of a scent, even if they are based on a biological mechanism.

And perhaps most surprisingly, the trigeminal system can be tricked too. Phenylethyl alcohol (PEA) has minimal action on the trigeminal system and is usually used as a neutral control odorant. However, in one of the studies², researchers administered PEA to subjects and warned them that it would be irritating and would sting. The EEG saw a sharp increase in P300 brain wave activity, indicating a state of high alertness, while subjects reported feeling an actual physical sting. Essentially, the brain “hallucinated” the stimulation to match the expectation. This mechanism is, of course, highly exploited in marketing communication.

Up to this point, we have looked at results obtained in controlled environments and with strict protocols. Moving this into practice is exactly what big companies are currently trying to solve, by launching research programs to generalize these effects, ensuring they hold true outside the lab for people in different cultures and countries. 

Yet, the functional claims require transparency. Just as the skincare market transitioned to a more informed, dermatological approach where consumers look for the active ingredients, fragrance buyers are evolving, too. It is crucial to distinguish between genuine biological impact and the psychological power of suggestion. 

By embracing a more open scientific approach with peer-reviewed publications, we can minimize the exploitation of “label power”, both in research and marketing communication, and better respond to a more demanding and smart consumer.

References

1. Baccarani A., Grondin S., Laflamme V., Brochard R. (2020). Relaxing and stimulating effects of odors on time perception and their modulation by expectancy. Frontiers in Neuroscience.
2. Bulsing P.J., Smeets M.A., Gemeinhardt C., Laverman M., Schuster B., Van den Hout M.A., Hummel T. (2007). Irritancy expectancy alters odor perception. Journal of Neurophysiology.
3. Brand, G. (2006). Olfactory/trigeminal interactions in nasal chemoreception. Neuroscience & Biobehavioral Reviews, 30(7), 908-17.
4. Daniels, J.K., Vermetten, E. (2016). Odor-induced recall of emotional memories in PTSD–Review and new paradigm for research. Experimental Neurology, 284, 168–180.
5. Eddin L.B., Jha N.K., Meeran M.F.N., Kesari K.K., Beiram R., Ojha S. (2021). Neuroprotective potential of limonene and limonene containing natural products. Molecules, 26(15), 4535.
6. Fukada, M., Kano, E., Miyoshi, M., Komaki, R., Watanabe, T. (2012). Effect of "rose essential oil" inhalation on stress-induced skin-barrier disruption in rats and humans. Chemical Senses, 37(4), 347-56.
7. Guzmán-Gutiérrez S.L, Bonilla-Jaime H., Gómez-Cansino R., Reyes-Chilpa R. (2015). Linalool and beta-pinene exert their antidepressant-like activity through the monoaminergic pathway. Life Sciences, 128, 24-9.
8. Hirasawa, Y., Shirasu, M., Okamoto, M., Touhara, K. (2019). Subjective unpleasantness of malodors induces a stress response. Psychoneuroendocrinology, 106, 206-215.
9. Iannilli E., Wiens S., Arshamian A., Seo H.S. (2013). A spatiotemporal comparison between olfactory and trigeminal event-related potentials. Chemical Senses.
10. Kaimoto T., Hatakeyama Y., Takahashi K., Imagawa T., Tominaga M., Ohta T. (2016). Transient receptor potential A1 channel activation by limonene and other monoterpenes. Chemical Senses, 41(8).
11. Kollndorfer K., Kowalczyk K., Frasnelli J., Hoche E., Unger E., Mueller C.A., Krajnik J., Trattnig S., Schöpf V. (2015). Same same but different. Different trigeminal chemoreceptors share the same central pathway. PLoS One, 10(3).
12. Lee, Y., Seo, Y., Lee, Y., & Lee, D. (2023). Dimensional emotions are represented by distinct topographical brain networks. International Journal of Clinical and Health Psychology, 23(4).
13. Li Q., Kobayashi M., Wakayama Y., Inagaki H., Katsumata M., Hirata Y., Hirata K., Shimizu T., Kawada T., Park B.J., Ohira T., Kagawa T., Miyazaki Y. (2009). Effect of phytoncide from trees on human natural killer cell function. International Journal of Immunopathology and Pharmacology.
14. Masaoka Y., Takayama M., Yajima H., Kawase A., Takakura N., Homma I. (2013). Analgesia Is Enhanced by Providing Information regarding Good Outcomes Associated with an Odor. Evidence-Based Complementary and Alternative Medicine.
15. Masuo, Y., Satou, T., Takemoto, H., & Koike, K. (2021). Smell and Stress Response in the Brain: Review of the Connection between Chemistry and Neuropharmacology. Molecules, 26(9).
16. Mei, L., Osakada, T., Lin, D. (2023). Hypothalamic control of innate social behaviors. Science, 382(6669), 399-404.
17. Moss M., Hewitt S., Moss L., Wesnes K. (2008). Modulation of cognitive performance and mood by aromas of peppermint and ylang-ylang. International Journal of Neuroscience, 118(1), 59-77.
18. Moss, M., Oliver, L. (2012). Plasma 1,8-cineole correlates with cognitive performance. Therapeutic Advances in Psychopharmacology, 2(3), 103-13.
19. Price, J.L., Slotnick, B.M., Revial, M.F. (1991). Olfactory projections to the hypothalamus. Journal of Comparative Neurology, 306(3), 447-61.
20. Raudenbush, B., Grayhem, R., Sears, T., Wilson, I. (2009). Effects of peppermint and cinnamon odor administration on simulated driving alertness, mood and workload. North American Journal of Psychology.
21. Shepherd, G.M. (2005). Perception without a thalamus how does olfaction do it? Neuron, 46(2), 166-8.
22. Shin, M.G., Bae, Y., Afzal, R., Kondoh, K., Lee, E.J. (2023). Olfactory modulation of stress-response neural circuits. Experimental & Molecular Medicine, 55(8), 1659-1671.