DEPRESSION AND ANXIETY
Aromatherapy
Aromatherapy is becoming an accepted therapy used for the treatment of side effects of conventional chemotherapy. Clary sage Salvia sclarea L. essential oil has therapeutic action for anxiety and depression in cancer patients. Aromatherapy affects metabolites in the body through the theory of olfaction and the link to the limbic system. There are no findings of the essential oils in the human urine after inhalation. The primary chemotypes for therapeutic action in clary sage essential oil (EO) are linalool and linalyl acetate. Clary sage EO affects the neurotransmitters; glutamate, aspartate, and phenylalanine. These neurotransmitters are associated with anxiety disorders. Clary sage EO has a therapeutic effect on depression by reducing cortisol and increasing 5-hydroxytryptamine (5-HT). The molecular properties of clary sage EO vary significantly based on the location of growth and genetic factors. The plant's production of the chemotype linalool is highest in clary sage EO grown at a high altitude in cold arid climates. The purpose of the paper is to assess the effects of clary sage S. sclarea L. essential oil on depression and anxiety in cancer patients.
A survey that measured people affected with cancer over a 5-year period in 2008 determined that 28.8 million people have cancer (Bray, F., Ren, J., Masuyer E., & Ferlay, J., 2013). It is now reported that one in three people will be diagnosed with cancer. Anxiety and depression are debilitating psychological aspects of people with cancer. The depth of the anxiety and depression of a cancer patient is misunderstood and often mistreated.
Exploratory research, conducted by Dauchy, Dolbeault, & Reich (2013), on depression in cancer patients, found that depression is often underdiagnosed and inadequately treated. The researchers found that the side effects of the cancer treatment and the depressive symptoms are often intertwined. They found that depression has a major impact on the quality of life, communication with family and caregivers, periods of hospitalization, and reduced expectation of survival. Twenty research studies found no significant proof of the effectiveness of antidepressants on cancer patients. Doctors must consider the side effects of the combination of antidepressants and cancer treatment when prescribing antidepressants to cancer patients.
Research on the constituent monoterpenoid for the treatment of depression and anxiety has been shown to have therapeutic actions. The monoterpenoid, linalool, is the chemotype responsible for the therapeutic action. Clary sage EO has 10.4-23% of linalool. Lavender Lavandula angustifolia EO is another EO that is effective for the treatment of anxiety and depression with 25-40% linalool. Clary sage EO is also high in the ester, linalyl acetate, 45.3-61.8%. Esters have shown therapeutic actions as a sedative. EOs have different strengths of chemotypes based on the location of origin. The variance in chemotype strengths creates a challenge for researchers to generalize the studies, as well as for consumers to know what the therapeutic value is of the EO they are using.
A quasi-experimental, pretest-posttest designed research by McPherson & McGraw (2013) focused on analyzing complementary alternative medicine (CAM) to treat generalized anxiety disorder (GAD). The study created a pilot program that incorporated multiple CAM therapies focused on changing self-behaviors to alleviate GAD. The researchers used the Depression Anxiety Stress Scale -21 (DASS-21) and the GAD-7 scale for measuring pre-& post-treatment. The study analyzed 37 female volunteers seeking treatment at a military treatment facility. Sixty-eight percent completed the program. There were significant reductions in anxiety based on the GAD-7. Reductions were also found in the DASS-21, individually and overall. This study suggests that patients seeking therapy will learn and develop self-care behavior for the treatment of GAD.
Aromatherapy is found to alleviate symptoms caused by conventional cancer medicines. In the UK, aromatherapy has become the top complementary therapy to support cancer patients' side effects. In the US, clinical aromatherapy programs are in several large hospitals. Sclareol, a constituent found in clary sage EO, has a similar structure to estrogen. There is only a trace amount found in clary sage EO, but patients with estrogen-dependent cancers should not use clary sage EO (Buckle, 2015).
Boehm, Bussing, & Ostermann (2012) completed a descriptive systematic review of 18 clinical trials and several preclinical trials on the benefits of aromatherapy for cancer patients and found that there were no long-term effects of aromatherapy massage on cancer patients. The review did find improvements in anxiety and depression that lasted up to 8 weeks after treatment. The researchers concluded the theory of the nature of olfaction and the link to the limbic system as the cause of the therapeutic action. The patient’s expectation and perception had a direct effect on the outcome of the treatment.
Leo, Cho, and Kang (2014) focused on the effect of aromatherapy with clary sage EO on the neurotransmitter level change in blood plasma. The participants, 22 menopausal women in their 50’s, were categorized into two groups, normal and depression tendency, based on the Korean version of Beck Depression Inventory -I (KDBI-I), KBDI -II, and the Korean version of the Self-Rating Depression Scale. The principal chemotypes in the clary sage EO used were linalyl acetate at 63.99% and linalool at 20.99%. The participants smelled a gauze dabbed with clary sage EO two times over a 3 hour period for 5 minutes. Thirty minutes after each time the participant smelled clary sage EO, the participants had blood drawn. Neurotransmitters measured in the blood samples via ADVIA Centaur Chemist Analyzer found the depressive group had a reduction of 31% in the KBDI-II and a reduction of 36% in the Self-Rating Depression Scale Inventory. The normal group had a reduction of 16% and 8.3% respectively. This study showed that clary sage EO has an anti-depressant effect, by reducing cortisol and increasing 5-HT. It is difficult to generalize the study due to the small sample size.
Seol et al. (2010) focused on identifying the regulatory mechanisms of four EOs that have antidepressant effects in rats. The EOs used in the study were chamomile Anthemis nabiltis EO, clary sage S. sclarea L. EO, rosemary Rosemarinus officinalis EO, and lavender L. angustifolia EO. The researchers analyzed the immobility time in a forced swim test (FST) of rats injected with agonist and antagonist drugs before treatment with EOs. The researchers determined the effects of the EO in the rat after injection or inhalation, by analyzing immobility time using the FST. The enzyme-linked immunosorbent assay (ELISA) was used to assess the serum levels of corticosterone in the rats. After inhalation of clary sage EO, the rats showed the least immobility time. The reduction in immobility time is a verification that clary sage EO has antidepressant therapeutic action. The study also concluded that the antidepressant therapeutic action of clary sage EO was through the DAnergic pathway. Their finding suggests that clary sage EO could be developed as an anti-depressant.
Aprotosoaie, Hancianu, Costache, & Miron, (2014) reviewed the molecular activity of linalool and listed clary sage EO as a racemate with 10-21% linalool. The most important therapeutic actions of linalool are central nervous system depressant effects, analgesic, and anti-inflammatory.
Baber et al. (2015) completed a systematic review on information regarding therapeutic, medical, psychological, olfactory, massage aromatherapy, among other things. The researchers found many published reports citing EO's usefulness in cancer and labor pain. Clary sage EO was found to contain linalool, linalyl acetate, among other chemotypes. Recent studies of clary sage EO indicate its effectiveness in controlling cortisol levels in women.
Yani et al. (2012) conducted a clinical trial on rats to evaluate the alteration of metabolites in rats with induced anxiety and the effect of aromas treatment. Brain tissue and urinary metabonomic analysis using gas chromatography time-of-flight mass spectrometry were used to measure the change. The researchers looked at neurotransmitters among other things in the brain. The anxiolytic effect was also evaluated comparing rats exposed to EO to rats not exposed. The EOs used were lavender L. augustifolia EO, clary sage S. sclarea L. EO, sandalwood Santalum album EO, and orange Citrus sinensis EO. Researchers used the elevated plus-maze, an animal model of anxiety, to analyze the effects of the EO on 40 Wistar rats. The researchers detected 50 differentially expressed metabolites in the brain tissue, believed to be induced by the aromas. The neurotransmitters glutamate, aspartate, and phenylalanine associated with anxiety disorders increased after EO inhalation. GABA, a chemical messenger in the brain which binds to neurons, reduced the activity of the neurons. Researchers believe GABA controls fear and anxiety when neurons are overexcited. Previous research shows that inhalation of linalool increased the effect of the action of GABA. According to the article, this was the first study that proved that the metabonomics approach could capture metabolic changes and pinpoint the pathways in anxiety-related behavior.
Zhang, Wu, Chen, Yao, Liu, Pan et al. (2013) conducted a clinical study in which they measured metabolic changes in participants after ten days of aroma inhalation. The participants were 39 female volunteers with mild anxiety. The participants completed a double-blind Symptom Check List-90 (SCL90) test. This test included nine subscales, including depression and anxiety, among other disorders. The EOs used were lavender L. augustifolia EO and clary sage S. sclarea L. EO from China, sandalwood S. album EO from India, and orange C. sinensis EO from the US. The prominent chemotypes found in these EOs were linalool along with 32 other chemicals. The inhalation process was induced by closing all windows and doors and infusing the room for 45 minutes for ten consecutive days. Urine metabolite profiling was performed utilizing the Waters ACQUITY UPLC system. The researchers found twenty-nine differentially expressed metabolites in the urine after inhalation, no EOs were detected. The anxiety, phobic anxiety, obsessive-compulsive, and depression were significantly different after EO exposure. The difference indicated that EO’s relax anxious mood and have some effect on mood adjustment. Some individuals were not affected, which indicated that individual experience of odor might affect response. The conclusion was that there were metabolic changes in the urine from the daily infusion.
Kaur et al. (2015) conducted a research study to analyze the different molecular properties of clary sage EO grown in different places from seed to harvest. They found the highest production of linalool in a cold arid climate. The researchers selected three different climate zones in the Western Himalayas for the study; subtropical, temperate, and cold arid. The cold arid region produced the highest percentage of linalool, 46.56%. The temperate region produced 41.83% linalool, and the subtropical region produced 30.5% linalool. The main chemotypes found in the full flowering stage are linalyl acetate, linalool, and germacrene D.
Hatipoglu et al. (2016) identified 108 volatile organic compounds (VOC) in 45 Anatolian Salvia species. The researchers used the Thermal Desorption -GC-MS technique to assess the VOCs. They identified ten classes of compounds based on their chemical structure. The main constituent found in the salvia species is a monoterpene. The researchers found that the yield of VOC and the percentage of each component were highly variable. The EO composition was found to be influenced by genetic and environmental factors. The main EO components found in Clary sage EO were germacrene D, B-caryophyllene, linalool, spathulenol, a-copaene, and sclareoloxide.
The purpose of this literature review is to analyze the research on clary sage reported on anxiety and depression for cancer patients. There were seven articles found supporting clary sage or the chemotype linalool with effective therapeutic actions on anxiety and depression. Most of these studies found were small and consisted of volunteers, which makes it difficult to generalize. Some articles only specified the chemotype linalool, not the specific EO in the study. Lavender L. augustifolia EO may be more effective as an antidepressant with 25-38% linalool. Most research found on clary sage S. sclarea L. EO supported the therapeutic effect on dysmenorrhea, menstrual cramps. Clary sage S. sclarea L. EO is an effective essential oil for treating anxiety and depression in cancer patients
Cancer affects over 28.8 million people throughout the world. Anxiety and depression are significant problems in people with cancer. It can affect their overall wellbeing, as well as their communication with caregivers, the length of hospitalization, pain tolerance, and length of survival. Clinical depression, partially caused by a biochemical imbalance of neuroendocrine, include 5-HT, thyroid-stimulating hormone (TSH), and corticosterone. People with depression show decreased plasma 5-HT metabolism. The decrease in 5-HT can affect mood (Lee, Cho, & Kang, 2014). Clary sage EO has been shown to reduce cortisol and increase 5 -HT. Clary sage EO increases the neurotransmitter; glutamate, aspartate, and phenylalanine, associated with anxiety disorders. The linalool in clary sage S. sclarea L. EO may affect GABA, which controls fear and anxiety when neurons become overexcited.
Aromatherapy has become more popular as a CAM treatment of side effects caused by conventional cancer medication. It is the top complementary therapy to support cancer patients in the UK. In the UK 40.6% of the cancer population were found to use aromatherapy (Boehm, Bussing, & Ostermqnn, 2012). The monoterpenoid, linalool, has been shown to have a therapeutic effect on depression. Linalool has strong therapeutic actions for central nervous system depressant effects, analgesic, and anti-inflammatory. The ester, linalyl acetate, has been shown to have a sedative effect. Clary sage S. sclarea L. EO has 10-21% linalool and 64% of linalyl acetate (Aprotosoaie, Hancianu, Cotache, & Miron, 2014). Clary sage S. sclarea L. EO has a trace amount of the chemotype sclareol. This chemotype has a similar structure to estrogen. Cancer patients with estrogen-dependent cancer should not use clary sage (Buckle, 2015).
Clary sage S. sclarea L. EO has a therapeutic action for anxiety and depression in cancer patients by reducing cortisol and increasing 5 -HT. Massage therapy using clary sage S. sclarea L. EO has been shown to improve anxiety and depression in cancer patients for up to eight weeks after treatment. The nature of the olfaction system and the link to the limbic system are the primary cause of this therapeutic action. Studies of inhalation of clary sage S. sclarea L. EO did not report any findings of EO’s in the urine. The person’s expectation and perception also play an important role in the therapeutic action of clary sage S. sclarea L. EO.
There was very little research found on clary sage S. sclarea L. EO in vivo on human participants in respect to therapeutic actions for depression and anxiety. The studies found on human participants were on females and with less than 50 participants. All participants were volunteers or seeking treatment, therefore the results were possibly manifested by the expectation of the participant. The other in vivo studies were conducted on rats. The chemotypes found in clary sage S. sclarea L. EO have been found to have therapeutic actions for depression and anxiety, further research needs to be conducted on humans.
There is evidence that clary sage S. sclarea L. EO has therapeutic action for anxiety and depression. Further research needs to be conducted on larger groups of male and female participants who are not seeking treatment. Further research needs to be conducted on the method of therapeutic action. In human studies, it appears that the therapeutic effect is secondary via the olfaction and the limbic system. In the rat studies, there was evidence of the EOs in the urine and in the brain tissue
Linalool and linalyl acetate is the chemotypes responsible for the therapeutic action. The percentage of these chemotypes is highly variable in clary sage S. sclarea L. EO. The genetic factors, climate, altitude, and harvest time determine the variability in molecular properties of the EOs found in clary sage S. sclarea L. EO. Further research identifying the molecular properties and the identification label on the EOs purchased by the consumer would enable consumers to select the appropriate EO for therapeutic action.
References:
Aprotosoaie, A. C., Hancianu, M., Costache, I., & Miron, A. (2014). Linalool: a review on a
key odorant molecule with valuable biological properties. Flavour Fragrance Journal. 29,
193-219.
Babar, A., Naser, A. A., Shams, S., Ahamad, A., Khan, S. A., Anwar, F. (2015). Essential oils
used in aromatherapy: A systemic review. Asian Pacific Journal of Tropical Biomedicine.
5(8): 601-611. Retrieved from: http:/dx.doi.org/10.1016/j.apjtb.2015.05.007
Boehm, K., Bussing, A., & Ostermann, T. (2012). Aromatherapy as an adjuvant treatment in
cancer care – A descriptive systematic review. African Networks on Ethnomedicines,
0 (4): 503-518. Retrieved from: http:/dx.doi.org/10.4314/ajtcam.v9i4.7
Bray, F., Ren, J., Masuyer E., & Ferlay, J. (2013). Global estimates of cancer prevalence in 27
sites in the adult population in 2008. International Journal of Cancer. 132 (5): 1133-45.
Buckle, J. (2015). Clinical aromatherapy essential oils in healthcare. 15-31, 306-318. St Louis,
MO: Elsevier Inc.
Dauchy, S., Dolbeault, S. & Reich, M. (2013). Depression in cancer patients. The European
CanCer Organisation. http://dx.doi.org/10.1016/j.ejcsup.2013.07.006
Hatipoglu, S. D., Zorlu, N., Dirmenci, T., Goren, A. C., Ozturk, T., & Topcu, G. (2016).
Determination of volatile organic compounds in forty five salvia species by Thermal
Desorption-GC-MS technique. Academy of Chemistry of Globe Publications. Retrieved
from: www.acgpubs.org/RNP
Kaur, T., Bhat, H., Bhat, R., Kumar, A., Bindu, K., Koul, S., & Vyas, D. (2015). Physio-Chemical
and antioxidant profiling of Salvia sclarea L. at different climates in the north-western
Himalayas. Polish Academy of Sciences, (37): 132.
Lee, K., Cho, E., & Kang, Y. (2014). Changes in 5-hydroxytryptamine and cortisol plasma
levels in menopausal women after inhalation of clary sage oil. Phytotherapy Research. 28,
1599-1605.
McPherson, F., McGraw, L. (2013). Treating generalized anxiety disorder using
complementary and alternative medicine. Alternative Therapies Sep/Oct 2013 Vol 19
No 5.
Seol, G. H., Shim, H. S., Kim, P., Moon, H. K., Lee, K.H., Shim, I., Suh, S. H., Min, S. S.,
(2010). Antidepressant-like effect of Salvia sclarea is explained by modulation of
dopamine activities in rats. Journal of Ethnopharmacology. 130, 187-190.
Yani, W., Zhange, Y., Guoxiang, X., Zhao, A., Xiaolan, P., Chen, T., Hu, Y., Liu, Y., Cheng, Y.,
Chi, Y., Yao, L. & Jia, W. (2012). The metabolic responses to aerial diffusion of essential
oils. PLOS One Volume 7 Issue 9 Retrieved from: www.plosone.org.
Zhang, Y., Wu, Y, Chen, T., Yao, L., Liu, J., Pan, X., Hu, Y., Zhae, A., Xie, G., & Wei, J. (2013).
Assessing the metabolic effects of aromatherapy in human volunteers. Evidence-Based
Complementary and Alternative Medicine. Volume 2013, Article ID 3586381, 9 pages
http://dx.doi.org/10.1155/2013/356381
KMiller 7/2017