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Editor’s Note: This review covers numerous human clinical trials and basic science research to begin the process of exploring an interesting treatment modality, essential oils, for an all-too-common condition, depression. As Ms. Benedicto points out, there are some important clinical pearls in this area, even as we in the scientific and clinical community await more scientific rigor in the form of P values, confidence intervals, and large sample sizes. I look at this review for a glimpse into the potential therapeutic efficacy of essential oils, realizing that pilot studies, uncontrolled clinical trials, and case series need to be corroborated with more methodologically sound work. Hopefully, such future research can clarify dosing and treatment protocols that may be lacking in this preliminary review.
SYNOPSIS: The antidepressant effects of essential oils are promising, but more studies in humans beyond preliminary stages are needed.
SOURCE: de Sousa DP, Silva RHN, Silva EFD, Gavioli EC. Essential oils and their constituents: An alternative source for novel antidepressants. Molecules 2017; 22:e1290. doi: 10.3390/molecules22081290.
According to the World Health Organization, depression carries the heaviest burden of disability among mental disorders. Globally, the average prevalence for major depression is 4.7% or one out of 20 people.1 The prevalence is 5.9% in women and 3.8% in men. Depression causes symptoms that affect people of all ages, compromising quality of life and all areas from work to social relationships. The search for effective alternatives to traditional pharmaceuticals is imperative. de Sousa et al studied essential oils, their constituents, mechanism of action, and therapeutic potential for depressive disorders.
Aromatic, medicinal plants have been used for centuries. Essential oils are rich in bioactive compounds. Studies have shown that they enter the blood stream either by inhalation or ingestion to cause psychological effects that complement pharmacological interventions. Examples of studies that have been conducted are in the realm of sleep quality,2,3 anxiety,4,5 nicotine craving,6 and post-traumatic stress disorder.7 This study was conducted to review essential oils and their constituents for the treatment of depression, since there is evidence that isolated compounds of these essential oils have antidepressant actions.
The authors performed a search of English-language PubMed articles from 1995 to December 2015 about plants and essential oils that have antidepressant activity. Plants were identified by chemical name and the name of their bioactive compounds. The reason for selecting certain plant species was to evaluate the antidepressant activity and to identify the mechanism of action of oils or particular components of the oils.
Lavender. The most frequently studied essential oil for mood is lavender, as it has widely recognized anxiolytic effects.5 Using lavender oil capsules from Lavandula angustifolia (Lamiaceae) flowers, Bezerra et al conducted a pilot study as an adjuvant therapy for major depression in eight patients with symptoms of anxiety, insomnia, and psychomotor agitation for three weeks. All three symptoms improved in the participants of this case series.8
Diego et al examined the moods of otherwise healthy adult men after acute inhalation of lavender oil. EEG activity, alertness, and mood were assessed and found to increase/improve in the 40 male participants. The researchers found that subjects also performed math calculations more accurately and faster.9
In another pilot study, Conrad et al administered lavender and rose in an essential oil blend (L. angustifolia and rose) either topically or through inhalation to 28 postpartum women diagnosed with mild-to-moderate depression or anxiety in 15-minute sessions, twice a week for four consecutive weeks. The essential oils significantly relieved both depression and anxiety symptoms with no side effects.10
Clary sage (Salvia sclarea L.). In a pilot study of 22 menopausal women, Lee et al found that 5-HT serum levels increased from pre- to post-inhalation. Plasma cortisol levels also decreased significantly.11
Orange (Citrus sinensis). One controlled, randomized clinical pilot trial with men under conventional antidepressant treatment compared men who were treated with orange oil inhalation to those who had no essential oil inhalation. Overall mood improved significantly in the orange oil treatment group. The researchers also found that subjects in the treatment group had normalized neuroendocrine hormone levels and immune function, and that these benefits were better than what is seen with antidepressants.12
Wild ginger (Asarum heterotropoides) contains methyl eugenol as the main compound. Researchers suspect methyl eugenol is the main mediator of the antidepressant effects based on prior studies on rats with essential oils containing this compound. Immunohistochemistry found the mechanism of action to be increasing corticotrophin-releasing factor and tyrosine hydroxylase-positive cells and a decrease in the 5-HT-positive cells. This led researchers to believe the increased CRF and reduced monoamines to be the reason for antidepressant-like effects of wild ginger oil.
Lemon (Citrus limon) reduced immobility time in the forced swimming test (FST) in rats and mice and reduced locomotion and exploration, indicating a sedative effect in acute inhalation.13 Reduced immobility times is a similar effect that occurs to conventional antidepressant drugs.13,14 Studies indicate that the mediation by 5-HT and dopamine neurotransmission produces lemon’s antidepressant-like effects. The main monoterpenes involved in C. limon essential oil were limonene, geranyl acetate, and trans-limonene oxide.
Suriname cherry (Eugenia uniflora) was found to contain sesquiterpenes that induced antidepressant-like effects. One of the sesquiterpenes, beta-caryophyllene, acts as a CB2 receptor agonist, which is expressed in the brain and involved in modulation of anxiety and depressive states.15,16
Two groups from China have studied the use of Korean perilla (Perilla frutescens) for its antidepressant-like effects. Using the chronic unpredictable mild stress (CUMS) model of depression for animals, the researchers showed reversal in behavioral, neurochemical, and immunological changes caused by stress with P. frutescens L. Britton.17,18 Researchers also found reduced sucrose-preference in stressed mice, often related to anhedonia. More evidence is geared toward identifying release of pro-inflammatory cytokines in major depression. Administration of frutescens chronically and dose-dependently decreased the serum levels in CUMS mice. This essential oil also contains limonene and beta-caryophyllene, both studied for their antidepressant-like effects.
Clary sage (S. sclarea L.) causes antidepressant-like effects through mediation of the activation of dopamine and 5-HT neurotransmission with linalool and geraniol as the principal constituents involved.
Acute administration of clove (Syzygium aromaticum) showed reduced immobility time in mice in FST and tail suspension test (TST), reversed sucrose preference, and reduced eating in an unfamiliar environment. Chronic administration restored brain-derived neurotrophic factor (BDNF) in CUMS rats.19 Major compounds included eugenol, beta-caryophyllene, and eugenyl acetate, which have been shown to have antidepressant-like actions.20,21,22
In acute administration of the essential oil from red cedar (Toona ciliata var. yunnanensis), there was an increase in hippocampal 5-HT, noradrenaline, dopamine, and BDNF. Additional studies are needed to isolate the effects of oil compounds found in red cedar.
Indian valerian (Valeriana wallichii) oil also decreased immobility time of mice in the FST. There is also evidence that the nitric oxide signaling pathway is involved and causes an acute antidepressant-like effect. Additional studies are needed to identify the effects of isolated compounds of Indian valerian for depression.
Eugenol and linalool are the most studied compounds from essential oils such as the ones discussed above. The most common antidepressant-like actions from these constituents are shown in FST and TST. Eugenol targets the monoamine oxidase (MAO) enzyme, by inhibiting MAOA activity and chronic administration increases BDNF, which is also a MAO shared by antidepressants.22 Acute administration of linalool, from lavender and clary sage essential oils, shows activation of monoamine 5-HT1A and alpha2-receptors. Relevant to psychological pathology, past research has found an association between pro-inflammatory cytokines and depressive symptoms.
This article presents a breadth of information regarding the research behind essential oils, specific chemical constituents, and their antidepressant actions. Although this literature review showed promising potential for the use of essential oils for depression, more studies are needed.
Risks involved with certain essential oils that were not mentioned in the review include skin irritation, phototoxicity, interactions with drugs, and toxicity, if ingested. Most of the research presented here was conducted on animals, so more human research is necessary to confirm clinical efficacy of the antidepressant properties described. BDNF and monoamine concentrations are the most noted mechanisms of action mentioned in this review relevant to the antidepressant efficacy of essential oils. More specifically, essential oils that contain the compounds eugenol and linalool, which increase BDNF and extracellular monoamine concentrations, appear to be the most encouraging. Plants that contain these oils are listed in Table 1.
The authors made the intuitive leap that since isolated constituents show a benefit, the diversity of the chemically active parts working together may have a more positive, even synergistic, effect on depression. This review mentioned a possible anti-inflammatory effect of some of the isolated compounds as mediators to the antidepressant actions. There is a growing body of research linking high concentrations of pro-inflammatory cytokines and depression symptoms.24
Since both human and animal studies have shown the positive psychological effects of essential oils, there is a possibility that they may be useful as compliment to pharmaceuticals. Neuroplasticity, which is proven to improve depressive symptoms, is induced by BDNF. BDNF increases with the plant compounds mentioned above and may be beneficial as a complement to pharmacotherapy. Although the data are accumulating about the various mechanisms by which the isolated compounds may have physiological effects and some promising preliminary clinical benefits, the overall clinical application requires more research.
The popularity of aromatherapy has grown as more consumers move away from synthetic compounds and into more natural solutions. For the most part, essential oils may offer a possible alternative or complement to pharmaceuticals in the overall clinical picture of depression. This is particularly important to consider if patients request a more holistic approach. High-quality oils require a large amount of plant material, making the price of some oils expensive, which could be a limiting factor in a clinical setting. As with any dietary supplements, it is important to choose reputable products and companies to avoid concerns about adulteration, contamination, and misrepresentation of label claims, although there is no reason to think that this is a specific problem to essential oils.
The statistics surrounding depression are troubling and continue to rise in all demographics.23 Since depression is one of the most prevalent mental disorders, the search is on for effective integrative health therapeutics; essential oils might have a role in this regard. Prior to knowing the true safety and benefit profile of essential oils for depression, clinical research needs to expand and provide methodologically sound clarifications to the interesting initial benefits as seen in the human research and basic science reviewed here.
Financial Disclosure: Integrative Medicine Alert’s executive editor David Kiefer, MD; peer reviewer Suhani Bora, MD; AHC Media executive editor Leslie Coplin; editor Jonathan Springston; and editorial group manager Terrey L. Hatcher report no financial relationships relevant to this field of study.