Therapeutic use of smell

How different smells are being used for therapeutic purposes:


Many essential oils contain compounds which have active effects on the human nervous system and research is being carried out to determine what these are and exactly how they work. Essential oils are complex mixtures and this makes them more difficult to study but nevertheless in some cases the effects of the complete oil as well as the main component(s) have been studied.  Here are a few examples for which there is hard scientific evidence.

 Lemon essential oil as antidepressant
Studies on animals and humans have demonstrated the antidepressant properties of lemon essential oil.
How does lemon smell stimulus work?
Lemon essential oils are complex mixtures of chemical compounds like limonene, g-terpinene, citral, linalool and b-caryophyllene among others, which can be represented by three main classes: terpenes, oxygenates and sesquiterpenes. The most significant flavor compound is citral, while linalool possesses highly distinctive organoleptic characteristics. In addition, limonene, myrcene, octanal, and g-terpene among others contribute with high aroma flavor of lemon oil. Lemon essential oil normalises the immune system and neuroendocrine hormone levels. Changes in dopamine and serotonin neuron activity and norepinephrine levels are observed (Gamarra et al, 2006).



A lot of research has been done to study the effects and mechanisms of action of lemon oil:
1. Following treatment with lemon essential oil  Cherng-Wei and colleagues found significant differences in the concentrations of norepinephrine, dopamine, and serotonin in the prefrontal cortex, striatum, and hippocampus, which might, at least in part, account for the antidepressant effect of lemon essential oil.

2. Shibata's lab in Kurume University School of Medicine, Fukuoka, Japan demonstrated that citrus fragrance could restore stress-induced immunosuppression in mice (Shibata et al, 1990 1991).
3. Lemon odour, as well as its main component citral, were found to be antidepressant in rats. The effect was investigated with the forced swimming test, a standard, widely-used means for screening antidepressant effects pre-clinically (Komori et al, 1995).
4. The treatment with citrus fragrance normalised neuroendocrine hormone levels and immune function and was rather more effective than antidepressants (Komori et al, 1995).
5. Lemon balm (main constituent citronellal) exhibited modulation of mood and cognitive performance (Kennedy et al, 2003).
6. Lemon oil possesses anxiolytic, antidepressant-like effects via the suppression of dopamine activity related to enhanced serotonergic neurons (Komiya et al, 2006).


7. In normal human subjects lemon odour reliably enhanced positive mood (Kiecolt-Glaser et al, 2008).
8. Negative emotions became less intense during exposure to citrus odour (de Wijk and Zijlstra, 2012).
9. Subjective responses influence the effects of citrus odours and suggest the involvement of both pharmacological and psychological mechanisms in the response and while there may be benefits from citrus odours, any claims have to be balanced by the fact that any effects do not universally translate into physiological changes (Nagai et al, 2000).

Further reading
10. de Almeida AAC, Costa JP, de Carvalho RBF, de Sousa DP, de Freitas RM. Evaluation of acute toxicity of a natural compound (+)-limonene epoxide and its anxiolytic-like action. Brain Research. 2012;1448:56–62.
11. Shen J, Niijima A, Tanida M, Horii Y, Maeda K, Nagai K. Olfactory stimulation with scent of grapefruit oil affects autonomic nerves, lipolysis and appetite in rats. Neuroscience Letters. 2005;380(3):289–294.
12. Kang P, Suh SH, Min SS, Seol GH. The essential oil of Citrus bergamia Risso induces vasorelaxation of the mouse aorta by activating K + channels and inhibiting Ca 2+ influx. Journal of Pharmacy and Pharmacology. 2013;65(5):745–749.
13. Costa CARA, Cury TC, Cassettari BO, Takahira RK, Flório JC, Costa M. Citrus aurantium L. essential oil exhibits anxiolytic-like activity mediated by 5-HT1A-receptors and reduces cholesterol after repeated oral treatment. BMC Complementary and Alternative Medicine. 2013;13, article 42
14. Seo Yeon Choi, Purum Kang, Hui Su Lee, and Geun Hee Seol. Effects of Inhalation of Essential Oil of Citrus aurantium L. var. amara 1 on Menopausal Symptoms, Stress, and Estrogen in Postmenopausal Women: A Randomized Controlled Trial. Evid Based Complement Alternat Med. 2014; 2014: 796518. doi: 10.1155/2014/796518.
  • 1The most important compounds from the neroli oil from Citrus aurantium L., var. amara, are linalool (34.4%), linalyl acetate (11.3%) and limonene (10.9%). 

Vanilla

 Vanilla has positive associations, usually with childhood treats, and is known for its calming effect (see SIRC report).  The main component of vanilla is vanillin 
Vanillin activates the left-frontal regions of the brain more than control conditions or an unpleasant odour (2). The experience of positive emotion is associated with the left-frontal brain activation (1), this finding therefore indicates the positive nature of the odour of vanilla. Vanilla has pleasant associations and is increasingly added to food flavourings and perfumes. Vanilla odour has been shown to have taste-enhancing effects when paired with aspartame (an artificial sweetener) (5). Robin et al. (4) measured autonomic parameters (heart rate, skin temperature, resistance and potential and respiratory rate) and correlated these with hedonic ratings for a number of odours. They concluded that vanillin affected the autonomic parameters in a way that indicated an induced state of happiness. To counter anxiety in a clinical setting Redd et al. (3) used heliotropin, a vanilla-like fragrance that had been rated previously as relaxing and pleasant in pilot tests. They gave 30sec bursts to patients undergoing magnetic resonance imaging. This is a claustrophobic and stressful procedure, requiring patients to remain still for 1hr. The heliotropin reduced anxiety by 63% in patients who liked the smell.
Vanillin binds to vanilloid receptors in the central nervous system (in particular TRPV1 and TRPV3 receptors).
  1. Davidson, R.J. (1995) Cerebral asymmetry, emotion and affective style. In Davidson, R.J.  and Hugdahl, K. (Eds.), Brain Asymmetry. MIT Press, Cambridge, USA, pp. 361-387
  2. Kline JP, Blackhart GC, Woodward KM, Williams SR and Schwartz GER (2000) Anterior electroencephalographic asymmetry changes in elderly women in response to a pleasant and an unpleasant odour. Biol Psychol 542, 241-250.
  3. Redd WH, Manne SL, Peters B, Jacobsen PB, Schmidt H (1994) Fragrance administration to reduce anxiety during MR imaging. J Magn Reson Imaging 4, 623-626.
  4. Robin, O., Alaoui-Ismaili, O., Dittmar, A. and Vernet-Maury, E. (1999) Basic emotions evoked by eugenol odor differ according to the dental experience. A neurovegetative analysis. Chemical Senses 24, 327-335.
  5. Sakai, N., Kobayakawa, T., Gotow, N., Saito, S. and Imada, S. (2001) Enhancement of sweetness ratings of aspartame by a vanilla odor presented either by orthonasal or retronasal routes. Perceptual and Motor Skills 92(3), 1002-1008.

Rosemary
Rosemary has been widely recognised as a stimulant but the evidence for this is rather thin on the ground. The major ingredients of rosemary are borneol, verbenone and cineole (although there are many other ingredients and often the minority compounds contribute more to the odour, e.g. pinene, limonene, eucalyptol, terpinene). Rosemary has been reported to increase systolic blood pressure immediately after inhalation due to stimulating sympathetic nerve activity (4,3) as well as increasing breathing rate. Subjects reported feeling more alert, attentive and vigorous and cheerful. Smelling rosemary (and lavender) decreased cortisol levels (stress hormone) in saliva (1). Some interesting differences in the left hemisphere activation in newborns of depressed mothers have been shown in response to rosemary (and lavender). Activation of the left hemisphere indicates a response to a positive stimulus (2).
  1. Atsumi, T. and Tonosaki, K. (2007) Smelling lavender and rosemary increases free radical scavenging activity and decreases cortisol level in saliva. Psychiatry Research 150, 89-96.
  2. Fernandez, M., Hernandez-Reif, M., Field, T., Diogo, M., Sanders, C. and Roca, A. (2004) EEG during lavender and rosemary exposure in infants of depressed and non-depressed mothers. Infant Behavior & Development 27, 91-100.
  3. Hongratanaworakit, T. (2009) Simultaneous aromatherapy massage with rosemary oil on humans. Scientia Pharmaceutica 77, 375-387.
  4. Saeki, Y. and Shiohara, M. (2001) Physiological effects of inhaling fragrances. International Journal of Aromatherapy 11, 118-125.

 Peppermint
Peppermint oil has a high menthol content. The oil also contains menthone and carboxyl esters, particularly menthyl acetate. Peppermint has been shown to be a stimulating odour, to increase alertness, (Klemm et al, 1992; Stampi et al, 1996; Torii et al, 1988), improve performance in a mental task (Barker et al., 2003), a visual task (Warm et al., 1991) and to improve sports performance as demonstrated in many studies in Raudenbush's laboratory. As well as improving sports performance peppermint augments cognitive performance and administrative tasks (Moss et al, 2008; Barker et al, 2003) with suggestions that both cardiovascular and central nervous system mechanisms are involved (Umezu, Sakata and Ito, 2001; Meamarbashi and Rajabi 2013). Peppermint odour, when administered as a single stimulus, has been reported to have a variety of effects, from a decrease in the magnitude of beta waves, a decrease in the finger-tip skin temperature following a mental task, implying a decrease in arousal response (Satoh and Sugawara, 2003), to the opposite - an increase in exercise performance, blood pressure and respiratory rate in the young male students (Meamarbashi and Rajabi, 2013).
In spite of all this evidence the only benefit of peppermint oil reported by the National Center for Complementary and Integrative Health of the NIH in the US, updated in 2016, is for irritable bowel syndrome. I'm not sure what this says.  You may think that menthol helps when you have restricted airflow (e.g. during a cold) but this is an illusion! In a study by Beardsmore and colleagues in 2008, there was no effect of menthol on any of the spirometric measurements but there was a significant increase in the perception of nasal patency. Menthol activates cold receptors (TRPM8) and gives the impression of increased airflow.
  • Barker, S., Grayhem., P., Koon, J., Perkins, J., Whalen, A. and Raudenbush, B. (2003) Improved performance on clerical tasks associated with administration of peppermint odor. Perceptual & Motor Skills 97, 1007-1010.
  • Carskadon, M.A. and Herz, R.S. (2004) Minimal olfactory perception during sleep: why odor alarms will not work for humans. Sleep 27, 402-405.
  • Goel, N. and Lao, R.P. (2006) Sleep changes vary by odor perception in young adults. Biological Psychology 71, 341-349.
  • Klemm, W.R., Lutes, S.D., Hendrix, D.V. and Warrenberg, S. (1992) Topographical EEG maps of human responses to odor. Chemical Senses 17, 347-361.
  • Raudenbush, B., Corley, N. and Eppich, W. (2001) Enhancing athletic performance through the administration of peppermint odor. Journal of Sport and Exercise Psychology 23, 156-160.
  • Raudenbush, B., Koon, J., Meyer, B., Corley, N., and Flower, N. (2003) Effects of odorant administration on pain and psychophysiological measures in humans. North American Journal of Psychology 6, 361-370.
  • Raudenbush, B., Meyer, B., and Eppich, W. (2002) The effects of odors on objective and subjective measures of athletic performance. International Sport Journal 6, 14-27.
  • Stampi, C., Aguirre, A., Macchi, M. and Moore-Ede, M. (1996) Peppermint aroma as a countermeasure to sleepiness during driving simulation. Sleep Research 25, 112.
  • Torii, S., Fukuda, H., Kanemoto, H., Miyanchi, R., Hamauzu, Y. and Kawasaki, M. (1988) Contingent negative variation and the psychological effects of odour. In: Van Toller, S., Dodd, G.H. (eds.), Perfumery: The Psychology and Biology of Fragrance. Chapman Hall, New York, pp. 107-120.
  • Warm, J.S., Dember, W.N., Parasuraman, R. (1991) Effects of olfactory stimulation on performance and stress in a visual sustained task. Journal of the Society of Cosmetic Chemists 42, 199-210.


Lavender
Several recent studies of the effect of essential oils, in particular lavender and lemon balm, have avoiding the placebo effect by examining the effects on demented patients (3). The observed effects were improvement in agitation and a more controlled motor behaviour. Lavender has been shown in many studies to have relaxing and sedative properties. In animal studies it has been shown to reduce motility (2), in humans it had sedative effects (1), reduced anxiety in hospital patients (5), led to feelings of greater relaxation and promoted drowsiness (4) - although this latter study reported very confused findings regarding brain wave changes in response to lavender. Linalool, the main active ingredient of lavender has been shown to have sedative effects on humans (7) and to decrease systolic blood pressure and skin temperature (6). Linalool has in fact been extensively studied and its pharmacological effects are now quite well understood. Foremost among them is its anti-nociceptive (pain killing) effect the molecular mechanisms for which have now been elucidated and relate to its ability to block voltage-gated sodium channels in nerve.
  1. Buchbauer, G., Jirovetz, L., Jager, W., (1991)Aromatherapy: evidence for sedative effects of the essential oil of lavender after inhalation. Z Naturforsch 46, 1067-1072. 
  2. Buchbauer, G., Jirovetz, L., Jager, W., Plank, C. and Dietrich, H. (1993) Fragrance compounds and essential oils with sedative effects upon inhalation. Journal of Pharmaceutical Sciences 82, 660-664.
  3. Burns, A., Byrne, J., Ballard, C., Holmes, C. (2002) Sensory stimulation in  dementia. British Medial Journal 325, 1312-1313.
  4. Diego MA, Jones NA, Field T, Hernandez-Reif M, Schanberg S, Kuhn C, McAdam V, Galamaga R, Galamaga M. (1998) Aromatherapy positively affects mood, EEG patterns of alertness and math computations. Int J Neurosci. 96, 217-224.
  5. Dunn C, Sleep J and Collett D (1995) Sensing an improvement: an experimental study to ev4aluate the use of aromatherapy, massage, and periods of rest in an intensive care unit. J Adv Nursing 21, 34-40.
  6. Heuberger, E., Redhammer, S., and Buchbauer, G. (2004) Transdermal absorption of (-)-linalool induces autonomic deactivation but has no impact on ratings of well-being in humans. Neuropsychophamacology 29, 1925-1932.
  7. Sugawara, Y., Hara, C., Tamura, K., Fujii, T., Nakamura, K-I., Masujima, T. and Aoki, T. (1998) Sedative effect on humans of inhalation of essential oil of linalool: sensory evaluation and physiological measurements using optically active linalools. Analytica Chimica Acta, 365, 293-299.

Smell and light to treat depression and anxiety
For many years light and smell have been shown to have a positive impact on mood. Bright Light Therapy (BLT) is an established treatment for seasonal affective disorder (SAD) and mood disorders , having been successfully used for over 20 years. It has also been shown to be effective in other kinds of non-seasonal depression and, in Major Depressive Disorder (MDD) a randomised, placebo controlled trial demonstrated that BLT was comparable to antidepressant medication in effectiveness. Smell has been shown to have effects on mood, stress, anxiety and depression. My lab has demonstrated that a combination of fluctuating light and smell stimuli has a synergistic and positive effect on mood and physiological state (Dong & Jacob, 2016) as well as brainwave markers for depression and anxiety (Warden-Smith et al, 2017).

The Kodobio, a therapeutic device
 for the delivery of light+smell treatment
The Kodobio in use


It has been estimated that Common Mental Disorders affect 1 in 6 British adults every week with over half of these having a mixed anxiety and depressive disorder. In the USA, in any given one-year period, 13 million to 14 million people (which equates to approximately 6.6% if the US population) experience depression; globally, more than 350 million people of all ages suffer from the illness (WHO, 2012) and the annual incidence in UK is 36 per 1000 (NICE, 2004).


Electroconvulsive Therapy (ECT) is thought by some to be one of the fastest ways to relieve the symptoms of depression and the use of ECT is on the rise in the UK (Guardian, Monday 17 April 2017). It is generally given when other treatments, e.g. drug therapy, have failed. Neither ECT nor drug therapy are cures for depression and both can have significant adverse side-effects. In view of this it is important that new ways are developed to combat this growing problem.  In my lab we have developed a device to try to treat depression/anxiety - the Kodobio - "kodo-" is the appreciation of incense in Japanese. It uses fluctuating light and smell stimuli and has been shown to have beneficial properties for both physiological and psychological markers. For further information have a look at the Kodobio website or follow these links to publications documenting the effects of light & smell therapy; Dong & Jacob, 2016   Warden-Smith et al, 2017.


Light and smell stimulation - the basis of Kodobio Sensory Therapy
How does the light and smell stimulus work? It works by altering the pattern of brainwave activity. EEG alphawave power in the brain has been used as an index of brain activity. The brain in its resting state tends to produce alphawaves. Many studies have demonstrated that an increase in alphawave activity in the left frontal hemisphere is associated with an appetitive response, approach behaviour and positive experience. Low left frontal alphawave activity is associated with negative mood, depression and anhedonia. In normal subjects, the balance between right and left frontal alphawave activity (left-right) is positive. In depression the frontal alphawave asymmetry (FAA) becomes reversed - negative - and a reduction in left hemisphere activity is associated with anxiety and depression. FAA has been used as an objective measure of depression and anxiety; depressed and anxious individuals tend to exhibit greater relative right anterior EEG or negative asymmetry, FAA can predict future development of anxiety and depression, and this asymmetry has been shown to be a moderately stable individual difference in adults, irrespective of sex and history of depression.
Alphawaves recorded in our lab

Frontal alphawave asymmetry (FAA) can be measured in the brain in real time using EEG electrodes with software that, by Laplace transform, calculates and subtracts the power in the alpha frequency band (8-12Hz) for left and right hemispheres. This can be displayed in real time (see green line in figure above) or converted into a signal that relays the information about the sign and magnitude of the FAA. This is therefore a biofeedback signal for "mood state". The idea is to feedback this signal during the light and smell stimulus programme so the person knows when the stimulus is successful.
Kodobio goggles

Above is a prototype - the  Kodobio - which we have used in experimental testing. We have found benefits including; reduced blood pressure, heart rate, lower tension/anxiety/depression markers and the results are published in, (1) Physiology & Behavior and (2) Open Life Sciences.  

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