Smell and Mood (inc. Depression)

Smell has a major impact on our psychology and physiology. First, smell is the backdrop to our every waking moment and, uniquely among the senses, it functions during sleep. Smells stimulate memory, alert us to our surroundings, inform us about health and disease, help us to unconsciously select a suitable partner, are an important part of sex, change our mood, warn us of danger, stimulate appetite when we are hungry and suppress it when we are full and, as recent research has found, can be used therapeutically and clinically. Smell affects mood and can be used to change it.

Smell & anxiety | Smell & depression | The brain & depression | Remedies for depression | Smell & sleep | Smell & memory

Smell and anxiety

Anxiety is your body's natural response to stress. It's a feeling of fear or apprehension about what's to come. Some smells can help reduce anxiety. Vanilla has pleasant associations and is increasingly added to food flavourings and perfumes. Vanilla activates the left-frontal regions of the brain and since positive emotion is associated with the left-frontal brain activation, this finding indicates the positive nature of the odour of vanilla. From measurements of physiological parameters and hedonic ratings (pleasantness/unpleasantness) Robin et al (1999) concluded that the vanillin (the active ingredient of vanilla) effects indicated an induced state of happiness. Vanillin has been used to counter anxiety in a clinical setting - Redd et al. (1994) used heliotropin, a vanilla-like fragrance 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 may have some interesting effects on nociceptive (pain) pathways in the peripheral nervous system and the brain through its action on vanilloid receptors (TRPV1). Other agonists (activators) of TRPV1 receptor include capsaicin (the hot ingredient of chilli peppers), cannabinoids and heat above 43oC. Another vanilloid receptor agonist is component of frankincense - incensole acetate. This binds to TRPV3 receptors and reduces anxiety in mice (of which more below, see Remedies for Depression - ancient and modern).

Lavender and lemon balm. Several recent studies of the effect of essential oils, in particular lavender and lemon balm, have avoided the placebo effect by examining the effects on demented patients (reviewed by Burns et al., 2002). 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 (Buchbauer et al., 1993), in humans it had sedative effects (Buchbauer et al., 1991), reduced anxiety in hospital patients (Dunn et al., 1995), led to feelings of greater relaxation and promoted drowsiness (Diego et al., 1998) - 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 (Sugawara et al., 1998) and to decrease systolic blood pressure and skin temperature (Heuberger et al, 2004). 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.

Smell and depression

Depression (major depressive disorder) is a common and serious medical illness that negatively affects how you feel, the way you think and how you act. Fortunately, it is also treatable. Depression causes feelings of sadness and/or a loss of interest in activities once enjoyed (Google). Certain odours can act as antidepressants. Work on animals showed that citrus fragrance could restore stress-induced immunosuppression  and lemon odour was found to be antidepressant in rats. Citrus fragrance was given to depressive human subjects and the results indicated that the doses of antidepressants necessary for the treatment of depression could be markedly reduced. The treatment with citrus fragrance normalised neuroendocrine hormone levels and immune function and was rather more effective than antidepressants (see Therapeutic use of Smell for references for all this). In humans the inhalation of food and fruit odours sniffed from bottles or surreptitiously pumped into patients’ rooms was associated with a reduction in self-reported depressive mood.

Anosmia and depression. Anosmia can lead to depression. Kohli et al (2016) found patients with olfactory dysfunction, have symptoms of depression that worsen with severity of smell loss.

The brain and depression
Brodmann areas of the human brain

Scans have shown that BA25, located deep in the front portion of the brain, tends to be hyperactive in depressed people (Mayberg et al., 2005). Activity in this area becomes more normal as the symptoms of depression are relieved, either by medication or therapy. Deep brain stimulation (DBS) of BA25 with implanted electrodes has had some success (60%) in fully treatment-resistant depressed patients. In rats DBS of the nearest equivalent to BA25 in humans caused a large increase in serotonin in the hippocampus. A recent study found that Transcranial Magnetic Stimulation has been found to be effective treating depression when targeted specifically to Brodmann area 46 (on the cortex surface), an area with intrinsic functional connectivity (negative correlation) with area 25 [Fox et al, 2012]. In December 2015 the National Institute for Health and Care Excellence (NICE) approved rTMS (Repetitive Transcranial Magnetic Stimulation) as an effective and safe method of treating depression for patients in the UK.

Smell and depression treatment

Implanting electrodes into the brain and injecting electric currents is not without its problems and induces nausea and vomiting in some patients (and remember 40% didn't respond at all). Maybe there is a less invasive and drastic way of achieving something of the same effect. Sensory information is integrated in the orbitofrontal cortex of the brain, including Brodmann area (BA) 11 (Kringelbach, 2005). This area neighbours the subgenual anterior cingulate cortex (BA 25 - see picture of brain above), the area implicated in major depressive disorder (MDD), and is functionally connected to it. The hypothesis proposed here (mine!) is that activation of neighbouring BA11 by multiple sensory stimuli might achieve similar consequences to deep brain stimulation by engaging BA25 normalising its activity. This might impact upon MDD and related depressive disorders. The effect of the stimulation would be maintained by presentation of a fluctuating cycle. We have developed a device to do this and have tested it successfully on normal subjects (it works - see my page on Therapeutic use of smell). Now we need to test it on depressed patients.

Remedies for depression - ancient and modern

Incense  In Ayurvedic medicine, sandalwood is an important remedy for somatic and mental disorders. Santalol, a major component of sandalwood oil, has been reported to have central nervous system depressant effects such as sedation. The burning if incense has been an important part of religious and spiritual ceremonies for millennia. An ingredient of frankincense, “incensole”, has been shown to activate TRPV3 receptors, responsible for the perception of warmth in the skin (Moussaieff et al., 2008) and these receptors are also found in the brain. Cannabinoids (endogenous) are another class of compound that act at this receptor. Furthermore, incensole has been shown to have anxiolytic and anti-depressive-like behavioral effects in mice.
When the UK brought in the new law banning "legal highs" there was a suggestion that incense burning could be banned in churches because of the psychotropic effect of the compounds it contained (e.g. santalol, incensole).
You might ask, if this incensole has such beneficial effects, why is more fuss not made about it? Well, my guess is that, after a flurry of papers in 2007, 2008, there is an effort to commercialise a synthetic analogue of incensole - this is just a guess, but it could potentially be a new anxiolytic and anti-depressant, and, make some money for someone. Watch this space!

A recent perfume – Smiley – has been marketed as the world’s first antidepressant perfume. It contains phenylethylamine and theobromine. Phenylethylamine is a natural alkaloid and a psychoactive drug with stimulant effects. It is sold as a dietary supplement for purported mood and weight loss-related therapeutic effects. It achieved notoriety following a mention in the book “The Chemistry of Love” that chocolate was “loaded with PEA”. This got picked up by the media and the wire services and became the “chocolate theory of love”. There is little or no basis to this since when ingested phenylethylamine gets rapidly metabolised by monoamine oxidase. However, less is known about its fate upon sniffing and entry into the brain via the nasal route. Theobromine is an alkaloid from the cacao plant. It is a methylxanthine and has many similar effects to another common methylxanthine, caffeine. In modern medicine theobromine is a vasodilator, a diuretic and a heart stimulant.

Nitric oxide (NO) is a new potential treatment for depression - it regulates the activity of many major neurotransmitters involved in the pathophysiology of depression. NB nitric oxide is laughing gas - hahahaha. You can buy it in capsules and after many pop festivals they have to clear up the small capsules  -
Hippy Crack it's called!

Seasonal affective disorder (SAD)

The depression accompanying SAD has been found to be correlated with decreased smell function. Patients had a reduced ability to identify odours when presented to the right nostril (right side of brain) (Postolache et al., 1999). Depression, schizophrenia and seasonal affective disorder are all known to suppress the sense of smell. A study (Kruger et al., 2010) looked at the olfactory thresholds for normal versus depressed people. Non-depressed volunteers were able to detect the smell at a much lower level than the depressed volunteers. The depressed volunteers, with higher thresholds, had much smaller olfactory bulbs than their non-depressed counterparts; and, the more depressed the person was, the smaller their olfactory bulb was. Depression is known to inhibit neurogenesis, and it may prevent the olfactory bulb from growing as large as it should be. This raises an important question as to whether olfactory therapy could reverse the inhibition of neurogenesis thereby leading to an increased olfactory bulb volume. This is something for the future.
Bright light therapy has been used successfully for many years as a treatment for SAD and, more recently, has been found to be effective in treating Major Depressive Disorder (MDD). Certain smells can change mood and have anti-depressant effects. Have a look at my page the Therapeutic use of smell for more detail and for information on the enhanced benefit of simultaneous light and smell therapy on depression.

Light and smell fluctuating stimulation for depression

A device has been developed  - the KODOBIO - to deliver fluctuating smell and light stimulation and it has been shown to affect psychological state (reduced anxiety, depression, tension) and change physiological state (reduced blood pressure, heart rate and skin resistance). Goto Therapeutic use of smell.

Therapeutic use of smell memory. Smells can be conditioned to a particular psychophysiological state either by accident of by deliberate pairing. By accident you may be exposed to a particular smell when experiencing a very exciting happy event for example and this smell will evoke the memories of the event and the emotions surrounding it. But, more than this, the psychophysiological state experienced at the time can be re-induced (e.g. increased pulse, blood pressure etc). Several labs have, over the years, tried to take advantage of this phenomenon for medical treatment for example in the treatment of diabetes and epilepsy. My lab is trying to use it to treat depression (see Therapeutic use of smell).

Work by Walter Freeman (Freeman, 1991) has shown that smell memory is context dependent and can be modified in the light of new experience, implying that our olfactory sense is continuously dynamic, updating as we live and experience new things. More on this subject in Theories of Olfaction.


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