NeuroCalm Soothe® Technical Data

Nutrients/Herbs That May Assist

Lavender oil
Lemon balm
Melissa officinalis, leaf extract
L-theanine
Camellia sinensis (green tea), leaf extract

Actions

  • Modulate neural communication and support neuronal resilience
  • Promote hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) homeostasis
  • Enhance alpha brain wave activity

Clinical Applications

  • Mixed anxiety and depression
  • Anxiety and panic

Lavender Oil and Theanine for Anxiety, Panic and Low Mood

Background Technical Information

Anxiety and depression are highly prevalent in today’s society.[1-5] In fact, in 2017 3.2 million Australians were reported having an anxiety-like condition, with one in ten experiencing feelings of depression.[6] For more than 2,500 years physicians have used botanical medicines in the treatment of anxiety, panic attacks and depression.[7,8] The herb lemon balm, traditionally used for nervous disorders[9,10] was shown to improve resilience to stress whilst lowering anxiety, depression and sleep disturbances in human and animal clinical trials.[11,12] Likewise, L-theanine, an amino acid found in the leaves of the plant Camilla sinensis (green tea), provided anti-stress, anxiolytic and anti-depressant-like effects in both animal and human studies.[13-15] Equally, lavender oil is recognised for promoting mental wellbeing and reduced feelings of short and long term distress.[16-19] In animal and human studies lavender oil provided anxiolytic effects in the aftermath of stressful situations, markedly lowered anxiety-related restlessness and agitation, and exerted antidepressant effects.[20-23]

Actions

Modulate neural communication and support neuronal resilience

The anxiolytic effects of lavender oil result from an increase in extracellular serotonin and modulation of serotonin neurotransmission, particularly at the 5-HT1A receptor level.[5, 19, 23] The mood enhancing effects of lemon balm may be from the inhibition of monoamine oxidase, thereby supporting the serotonergic system, and inhibiting GABA transaminase, an enzyme involved in gamma aminobutyric acid (GABA) degradation.[9, 11, 12, 24]

L-theanine also has an affinity for glutamatergic receptors, being a modulator of both excitatory glutamate and inhibitory glycine, promoting a relaxed disposition.[13, 14, 25, 26] L-theanine’s regulatory effects on glutamate further influence GABA, where ingestion of L-theanine over two weeks lowered levels of glutamate and increased GABA in animals.[27] Interestingly, L-theanine increased levels of 5-HT and GABA in the central nervous system (CNS) within 20 to 30 minutes post ingestion.[28]

In addition, alterations in neurogenesis and neuroplasticity have been strongly implicated in the pathogenesis of mood disorders.[23, 26] Lavender oil enhanced neurogenesis and synaptogenesis as it heightened neurite outgrowth and increased the number of synapses in mature primary hippocampal neurons in vitro.[23] Lemon balm also promoted neurogenesis in a dose-dependent manner by increasing neuroblast proliferation and differentiation within the hippocampal dentate gyrus in animals.[9, 29] L-theanine supplementation in humans lead to a rise in serum brain derived neurotropic factor (BDNF) which was associated with improvements in dysphoric mood and anxiety scores, and an increase in hippocampal BDNF associated with antidepressant effects.[14, 15, 26, 30]

Promote hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) homeostasis

Well-established markers linked to a dysfunctional HPA axis and imbalanced ANS from the impact of stress on an individual include heart rate (HR), blood pressure, salivary secretory IgA (ssIgA), salivary alpha-amylase (sAA), cortisol measurements and heart rate variability.[25, 26, 31-33] The anxiolytic effects of lavender oil come from its regulation of the HPA axis thereby influencing plasma stress hormone levels, and modulating parasympathetic nervous system activity to balance the ANS.[33] Additionally, lemon balm improved mood and the stress response as it dose-dependently reduced serum corticosterone levels in animals,[9, 11] whilst decreasing HR and heart palpitation frequency in animals and humans.[34] Lastly, L-theanine significantly lowered stress hormones and modulated HPA axis activity in stress-inducing models, whilst providing anti-stress effects both acutely and long term at a dose of 200 mg daily.[14, 25, 26] At a dose of 200 mg twice daily, L-theanine lowered subjective stress and reduced sAA levels in students.[26]

Enhance alpha brain wave activity

Alpha brain waves are associated with elevated visual performance, improved accuracy and reaction whilst promoting a relaxed state.[13,14, 28, 35]Evidence suggests diminished alpha brain wave activity is associated with anxiety, and increasing alpha wave magnitude resulted in a calming effect in highly anxious individuals.[36] L-theanine elevated oscillatory brain activity in the alpha band in humans 30 minutes after ingestion, which accompanied an increase in neurotransmitters levels.[25] Further, L-theanine acted as a relaxing agent without causing drowsiness, slowed reflexes or impaired concentration.[13, 14, 28, 35]

Clinical Applications

Mixed anxiety and depression

Some individuals experiencing anxiety and depression do not meet the full diagnostic criteria for these conditions, and thus fall into the diagnosis of a mixed anxiety and depressive disorder (MADD).[4] Fortunately, lavender oil, lemon balm and L-theanine has been shown in several clinical trials (Table 1) to remarkably improve symptoms of MADD.

Table 1: Lavender oil, lemon balm and L-theanine in treatment of MADD

Condition

Study details

Outcome

Mixed anxiety and depression

Randomised double-blind placebo-controlled clinical trial(n=315); Lavender oil 80 mg/d or placebo for 10 weeks

Compared with placebo group, the lavender oil group experienced a statistically significant improvement in HAMA and MADRS total scores (p=0.008, p<0.001) from week 4 until week 10 (Figure 2).[4]

Chronic stable angina

Randomised double-blind placebo-controlled clinical trial (n=73) M. officinalis leaf extract 3,000 mg/d or placebo for 8 weeks

Group receiving lemon balm experienced remarkable reductions in anxiety, depression, stress (p<0.001) and sleep disturbances (p<0.05) compared with placebo group.[11]

Mild to moderate depression

Randomised double-blind clinical trial (n=45) M. officinalis leaf extract 2,000 mg/d or L. angustifolia 2,000 mg/d or fluoxetine 20 mg/d for 8 weeks

There were no marked differences in improvements between treatment groups with all three groups improving depressive symptoms and having similar decreases in HAMD scores, − 7.80, − 9.80, and − 8.46, L. angustifolia, fluoxetine and M. officinalis respectively.[24]

Stress-related anxiety and depression

Randomised double-blind placebo-controlled crossover trial (n=30);L-theanine 200 mg/d for 10 weeks

L-theanine group experienced significant improvements in depression, anxiety and sleep (p=0.019, 0.006 and 0.013) from baseline to post trial (Figure 3).[14]

Anxiety and panic

Common symptoms associated with anxiety include hypervigilance, poor concentration, fatigue, and sleep disturbances.[27, 37] For many, anxiety will be accompanied by panic attacks, defined as unexpected abrupt surges of intense fear or discomfort.[1, 38] Symptoms experienced during a panic attack include sweating, heart palpitations and accelerated HR.[39]

Clinical trials (Table 2) demonstrate lavender oil, lemon balm and L-theanine provide both anxiolytic and anti-stress effects, attenuating feelings of anxiety and panic.

Table 2: Lavender oil, lemon balm and L-theanine in treatment of anxiety and anxiety-associated symptoms.

Condition

Treatment & dose

Outcome

Anxiety disorders

Systematic review and meta-analysis (n=1149);Lavender oil 80 mg/d -160 mg/d or placebo for 6 - 10 weeks

Lavender oil dosed at 160 mg/d was superior in lowering HAMA score compared with 80 mg/d lavender oil dose, placebo, lorazepam (0.5 mg/d) and paroxetine (20 mg/d). Both doses of lavender oil significantly reduced HAMA score compared with placebo (p<0.001).[22]

Generalised anxiety disorder

Randomised double-blind double-placebo multicentre trial (n=536) Lavender oil 80-160 mg/d or placebo or paroxetine 20 mg/d for 10 weeks

Both doses of lavender oil were impressively superior to placebo in reducing HAMA scores (p<0.01, p<0.02), and had higher numbers of responders when weighed up against paroxetine and placebo (Figure 4). Lavender oil at 160 mg/d had greater numbers in remission compared with the other three interventions.[2]

Generalised anxiety disorder

Randomised double-blind multicentre trial (n=77) Lavender oil 80 mg/d or placebo or lorazepam 0.5 mg/d for 6 weeks

Lavender oil treatment was as effective as lorazepam in lowering HAMA scores in participants over the 6-week period. Decrease in total HAMA score was 54.8% and 53.6% in lavender oil and lorazepam respectfully.[40]

Subsyndromal[§§]

anxiety disorder

Randomised double-blind placebo-controlled multi-centre trial (n=216) Lavender oil 80 mg/d or placebo for 10 weeks

The group receiving the lavender oil experienced a clinically meaningful and statistically significant (p<0.001) decrease in HAMA scores over a period of 10 weeks (HAMA score decrease 16 versus 9.5, lavender oil versus placebo respectively).[2]

Subthreshold anxiety disorder

Randomised placebo-controlled trial (n=170); Lavender oil 80 mg/d or placebo for 10 weeks

A reduction in total HAMA score was 46.3% and 36.2% in lavender oil and placebo groups respectively. Decrease of at least 50% in HAMA score post trial was seen in 48.8% and 33.3% of lavender oil group and placebo group respectively, with remission achieved in 31.4% and 22.6% of lavender oil and placebo respectively.[41]

Anxiety

Review;M. officinalis leaf extract varied doses

Human trials showed lemon balm improved stress-induced negative mood, elevated feelings of calmness and decreased anxiety-associated symptoms and manifestations.[12]

Anxiety, negative mood and stress

Two double-blind placebo-controlled crossover trials (n=25, n=21); M. officinalis leaf extract 300 mg or 600 mg in a drink and yoghurt or placebo; 4 non-consecutive days.

Both lemon balm treatments were associated with improvements in mood. There was a significant reduction in state anxiety both 1 hour and 3 hours post consumption of the beverage containing the 300 mg dose (p<0.05). This dose was also associated with better working memory.[42]

Heart palpitations

M. officinalis

leaf extract

500 mg twice daily or

placebo for 2 weeks

The group receiving lemon balm experienced a 36.8% decrease from baseline to end of trial in the frequency of heart palpitations. Lemon balm provided a meaningful decrease in frequency of heart palpitations and the number of participants experiencing anxiety compared with the placebo group (p<0.0001, p=0.004).[39]

Stress-induced negative change in mood

Preliminary double-blind placebo-controlled balanced-crossover study (n=18) M. officinalis leaf extract 300 mg or 600 mg or placebo; for 3 non-consecutive days

When weighed up against the placebo, the 600 mg dose of lemon balm significantly increased self-ratings of calmness post stress-inducing tests (p=0.02) (Figure 5).[10]

Acute stress

Double-blind clinical trial (n=12) L-theanine 200 mg single dose

L-theanine lowered HR, sIgA and subjective perception of stress in comparison with placebo after acute stress test.[25]

Anxiety

Double-blind randomised placebo-controlled repeated measurement design protocol (n=18); L-theanine 200 mg or placebo single dose

L-theanine at 200 mg dose notably raised alpha band activity (p=0.0548) and markedly decreased HR (p=0.0016) for participants in the high anxiety propensity group.[28]

Anxiety and stress

Systematic review (n=250); L-theanine 200 mg/d – 400 mg/d or placebo or alprazolam 1 mg/d; Single dose – 8 weeks

Compared with placebo, L-theanine outstandingly lowered blood pressure (p=0.008, p=0.006), lowered HR, salivary sIgA, anxious mood, tension and subjective and self-rated stress response. L-theanine lowered subjective anxiety compared with placebo and alprazolam.[32]

Anxiety and stress

Cross-over randomised placebo-controlled trial (n=16) L-theanine 200 mg/d or placebo or caffeine 100 mg/d; 3 days

L-theanine reduced blood pressure induced by psychological stress in highly responsive individuals contrasted with the placebo. L-theanine lowered stress-induced tension and anxiety improving participants mood.[31]

Safety Information

Disclaimer: In the interest of supporting Healthcare Practitioners, all safety information provided at the time of publishing is in accordance with Natural Medicine Database (NATMED PRO), renowned for its professional monographs which include a thorough assessment of safety, warnings, and adverse effects.

For further information on specific interactions with medications, please contact Clinical Support on 1800 777 648, or via email, anz_clinicalsupport@metagenics.com

Pregnancy and Lactation

  • Insufficient reliable information available; avoid using.[43]

Contraindications

  • Contraindicated with Ephedrine, Nadolol (Corgard) and Atorvastatin (Lipitor); avoid this combination.[43]

References

[1] Andrews G, Bell C, Boyce P, et al. Royal Australian and New Zealand college of psychiatrists clinical practice guidelines for the treatment of panic disorder, social anxiety disorder and generalised anxiety disorder. Australian & New Zealand Journal of Psychiatry. 2018;52(12):1109-72. doi:10.1177/0004867418799453

[2] Kasper S, Gastpar M, Müller WE, et al. Silexan, an orally administered lavandula oil preparation, is effective in the treatment of 'subsyndromal' anxiety disorder: a randomized, double-blind, placebo controlled trial. Int Clin Psychopharmacol. 2010;25(5):277-87. doi:10.1097/YIC.0b013e32833b3242

[3] Garakani A, Murrough JW, Freire RC, et al. Pharmacotherapy of anxiety disorders: current and emerging treatment options. Front Psychiatry. 2020;11:595584. doi:10.3389/fpsyt.2020.595584

[4] Kasper S, Volz HP, Dienel A, et al. Efficacy of silexan in mixed anxiety-depression- a randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2016;26(2):331-340. doi:10.1016/j.euroneuro.2015.12.002

[5] Rahmati B, Kiasalari Z, Roghani M, et al. Antidepressant and anxiolytic activity of Lavandula officinalis aerial parts hydroalcoholic extract in scopolamine-treated rats. Pharm Biol. 2017;55(1):958-965. doi:10.1080/13880209.2017.1285320

[6] Mental health [Internet]. ABS. 2018 Dec 12th [Cited 2021 October 20th]. Available at: https://www.abs.gov.au/statistics/health/mental-health/mental-health/latest-release

[7] Sarris J, Panossian A, Schweitzer I, et al. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol. 2011;21(12):841-60. doi:10.1016/j.euroneuro.2011.04.002

[8] Glas G. A conceptual history of anxiety and depression. Medical Psychiatry. 2003;18;21:1-48.

[9] Yoo DY, Choi JH, Kim W, et al. Effects of Melissa officinalis L. (lemon balm) extract on neurogenesis associated with serum corticosterone and GABA in the mouse dentate gyrus. Neurochem Res. 2011;36(2):250-7. doi:10.1007/s11064-010-0312-2

[10] Kennedy DO, Little W, Scholey AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med. 2004;66(4):607-13. doi:10.1097/01.psy.0000132877.72833.71

[11] Haybar H, Javid AZ, Haghighizadeh MH, et al. The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina. Clin Nutr ESPEN. 2018;26:47-52. doi:10.1016/j.clnesp.2018.04.015

[12] Shakeri A, Sahebkar A, Javadi B. Melissa officinalis L. - A review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. 2016;188:204-28. doi:10.1016/j.jep.2016.05.010

[13] Dietz C, Dekker M. Effect of green tea phytochemicals on mood and cognition. Curr Pharm Des. 2017;23(19):2876-2905. doi:10.2174/1381612823666170105151800

[14] Hidese S, Ogawa S, Ota M, et al. Effects of L-theanine administration on stress-related symptoms and cognitive functions in healthy adults: a randomized controlled trial. Nutrients. 2019;11(10):2362. doi: 10.3390/nu11102362

[15] Miodownik C, Maayan R, Ratner Y, et al. Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients. Clin Neuropharmacol. 2011;34(4):155-60. doi:10.1097/WNF.0b013e318220d8c6

[16] Schuwald AM, Nöldner M, Wilmes T, et al. Lavender oil-potent anxiolytic properties via modulating voltage dependent calcium channels. PLoS One. 2013;8(4):e59998. doi:10.1371/journal.pone.0059998

[17] Rahmati B, Kiasalari Z, Roghani M, et al. Antidepressant and anxiolytic activity of Lavandula officinalis aerial parts hydroalcoholic extract in scopolamine-treated rats. Pharm Biol. 2017;55(1):958-965. doi:10.1080/13880209.2017.1285320

[18] Sayed AM, Morsy S, Tawfik GM, et al. The best route of administration of lavender for anxiety: a systematic review and network meta-analysis. Gen Hosp Psychiatry. 2020;64:33-40. doi:10.1016/j.genhosppsych.2020.02.001

[19] Baldinger P, Höflich AS, Mitterhauser M, et al. Effects of Silexan on the serotonin-1A receptor and microstructure of the human brain: a randomized, placebo-controlled, double-blind, cross-over study with molecular and structural neuroimaging. Int J Neuropsychopharmacol. 2014;18(4):pyu063. doi:10.1093/ijnp/pyu063

[20] Schuwald AM, Nöldner M, Wilmes T, et al. Lavender oil-potent anxiolytic properties via modulating voltage dependent calcium channels. PLoS One. 2013;8(4):e59998. doi:10.1371/journal.pone.0059998

[21] Rahmati B, Kiasalari Z, Roghani M, et al. Antidepressant and anxiolytic activity of Lavandula officinalis aerial parts hydroalcoholic extract in scopolamine-treated rats. Pharm Biol. 2017;55(1):958-965. doi:10.1080/13880209.2017.1285320

[22] Yap WS, Dolzhenko AV, Jalal Z, et al. Efficacy and safety of lavender essential oil (Silexan) capsules among patients suffering from anxiety disorders: a network meta-analysis. Sci Rep. 2019;9(1):18042. doi:10.1038/s41598-019-54529-9

[23] Müller WE, Sillani G, Schuwald A, et al. Pharmacological basis of the anxiolytic and antidepressant properties of Silexan®, an essential oil from the flowers of lavender. Neurochem Int. 2021;143:104899. doi:10.1016/j.neuint.2020.104899

[24] Araj-Khodaei M, Noorbala AA, Yarani R, et al. A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with fluoxetine for the treatment of depression. BMC Complement Med Ther. 2020;20(1):207. doi:10.1186/s12906-020-03003-5

[25] Kimura K, Ozeki M, Juneja LR, et al. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2007;74(1):39-45. doi:10.1016/j.biopsycho.2006.06.006

[26] Rothenberg DO, Zhang L. Mechanisms underlying the anti-depressive effects of regular tea consumption. Nutrients. 2019;11(6):1361. doi:10.3390/nu11061361

[27] Chesnut M, Harati S, Paredes P, et al. Stress markers for mental states and biotypes of depression and anxiety: a scoping review and preliminary illustrative analysis. Chronic Stress (Thousand Oaks). 2021;5:24705470211000338. doi:10.1177/24705470211000338

[28] Higashiyama A, Htay HH, Ozeki M, et al. Effects of l-theanine on attention and reaction time response. Journal of Functional Foods. 2011;3(3):171-8. doi:10.1016/j.jff.2011.03.009

[29] Naseri M, Arabi Mianroodi R, Pakzad Z, et al. The effect of Melissa officinalis L. extract on learning and memory: Involvement of hippocampal expression of nitric oxide synthase and brain-derived neurotrophic factor in diabetic rats. J Ethnopharmacol. 2021;276:114210. doi:10.1016/j.jep.2021.114210

[30] Yoneda Y, Kawada K, Kuramoto N. Selective upregulation by theanine of Slc38a1 expression in neural stem cell for brain wellness. Molecules. 2020;25(2):347. doi:10.3390/molecules25020347

[31] Yoto A, Motoki M, Murao S, et al. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012;31(1):28. doi: 10.1186/1880-6805-31-28

[32] Williams JL, Everett JM, D'Cunha NM, et al. The effects of green tea amino acid L-theanine consumption on the ability to manage stress and anxiety levels: a systematic review. Plant Foods Hum Nutr. 2020;75(1):12-23. doi:10.1007/s11130-019-00771-5

[33] Bradley BF, Brown SL, Chu S, et al. Effects of orally administered lavender essential oil on responses to anxiety-provoking film clips. Hum Psychopharmacol. 2009;24(4):319-30. doi:10.1002/hup.1016. PMID: 19382124

[34] Draginic N, Jakovljevic V, Andjic M, et al. Melissa officinalis L. as a nutritional strategy for cardioprotection. Front Physiol. 2021;12:661778. doi:10.3389/fphys.2021.661778

[35] Saeed M, Naveed M, Arif M, et al. Green tea (Camellia sinensis) and l-theanine: medicinal values and beneficial applications in humans-a comprehensive review. Biomed Pharmacother. 2017;95:1260-1275. doi:10.1016/j.biopha.2017.09.024

[36] Hou Y, Zhang S, Li N, et al. Neurofeedback training improves anxiety trait and depressive symptom in GAD. Brain Behav. 2021;11(3):e02024. doi:10.1002/brb3.2024

[37] Gautam S, Jain A, Gautam M, et al. Clinical practice guidelines for the management of generalised anxiety disorder (GAD) and panic disorder (PD). Indian J Psychiatry. 2017;59(Suppl 1):S67-S73. doi:10.4103/0019-5545.196975

[38] Cackovic C, Nazir S, Marwaha R. Panic Disorder. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430973/

[39] Alijaniha F, Naseri M, Afsharypuor S, et al. Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. J Ethnopharmacol. 2015;164:378-84. doi:10.1016/j.jep.2015.02.007

[40] Woelk H, Schläfke S. A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder. Phytomedicine. 2010;17(2):94-9. doi:10.1016/j.phymed.2009.10.006

[41] Kasper S, Anghelescu I, Dienel A. Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep--A randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2015;25(11):1960-7. doi:10.1016/j.euroneuro.2015.07.024

[42] Scholey A, Gibbs A, Neale C, et al. Anti-stress effects of lemon balm-containing foods. Nutrients. 2014;6(11):4805-21. doi:10.3390/nu6114805

[43] Natural Medicines Database. AusDi; 2024. Accessed September 20, 2024. https://ausdi.hcn.com.au/

Back to Technical Data

Related Posts

Live webinars, on-demand courses, and thought-leader panels—all at your fingertips.

View All Articles
MetaRelax Daily Product Detailer

MetaRelax Daily Product Detailer

MetaRelax Daily Technical Data

MetaRelax Daily Technical Data

MetaRelax Daily Product Detailer

MetaRelax Daily Product Detailer

UltraFlora Triple Action Biotic Detailer

UltraFlora Triple Action Biotic Detailer