Anxiety disorders are some of the most common mood conditions presenting in Australian patients.[1] They can take many forms ranging from specific phobias to generalised anxiety disorder, can affect people at all stages of life, and can often co-occur alongside other mood disorders such as post-traumatic stress disorder and depression.

What are the features of anxiety?

Although anxiety may be classified in several different ways according to the presentation, the underlying neurobiology shares some common features. The following all play a role in the development of anxiety disorders[2]:

• The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis
• Alterations in the levels of various neurotransmitters
• Disruptions in the signalling of the endocannabinoid system

The HPA axis is the primary regulator of our stress response system. In times of danger, it activates our ‘flight, fright or fight’ responses to help protect us from external threats. At other times, the function of the HPA axis is down-regulated, allowing us to return to a state of ‘resting and digesting’ where our body is relaxed and can focus on functions such as digestion, cellular repair and reproduction. For those with anxiety, the HPA axis becomes inappropriately activated in response to everyday activities, leading to the symptoms commonly seen in these disorders including a racing mind, hyperventilation, elevated heart rate and sweating.[3]

Emerging evidence suggests that the endocannabinoid system (ECS) is intimately involved in the regulation of mood and stress, and that perturbations in this system may exacerbate anxiety disorders. The ECS is a widely distributed system comprised of various endocannabinoids, receptors and enzymes. While its function is still being fully elucidated, the ECS plays a key role in maintaining homeostasis in the central nervous, metabolic and immune systems.[4] Lower levels of endocannabinoids have been observed in those with depression and anxiety, while animal studies have demonstrated that the anxiolytic effect of several therapeutic substances is mediated through their action on the ECS.[5]

How herbs can help address anxiety and depression

Given the complexity of neurochemistry, the HPA axis and ECS, it can be confusing to know how to address them in relation to those presenting with anxiety and/or depression. Thankfully, we are now learning that many of the herbs traditionally used for these conditions help to modulate targets across all these systems. These new understandings provide insight into the mechanisms that make these herbs so clinically effective.

Lavender

Lavender has been shown in numerous clinical trials to be an effective treatment for anxiety and depression. Lavender inhibits the enzyme fatty acid amide hydrolase (FAAH), which breaks down endogenous cannabinoids.[6] The inhibition of this enzyme helps to raise endocannabinoid levels and has been shown to be a useful target for anti-anxiety therapeutics.[7] Lavender oil also contains a substance called beta-caryophyllene, which binds to and activates the CB2 receptor. Outside of the ECS, lavender modulates the HPA axis, having a demonstrated normalising effect on various markers of HPA axis dysfunction, including plasma cortisol levels, salivary immunoglobulin A (IgA) and heart rate variability.[8] Additionally, lavender can increase the levels of neurotransmitters including serotonin and norepinephrine, which can help in providing additional support when the patient is presenting with both anxiety and depression.[9]

Lemon balm

Lemon balm, another time-honoured herbal anxiolytic, additionally helps to modulate the activity of the HPA axis by reducing neuronal excitability.[10] Both animal and human studies have demonstrated lemon balm’s ability to improve markers of chronic stress (including plasma cortisol) and attenuate the physical symptoms associated with anxiety such as rapid heartbeat and excessive sweating.[11]

L-theanine derived from green tea

L-theanine derived from green tea has also been shown to be an effective intervention for anxiety, exerting a similar modulating effect on the HPA axis, while promoting alpha brainwave activity and acting on the gamma-aminobutyric acid (GABA) receptor directly, to provide rapid relief for anxiety symptoms.[12] Systematic reviews have confirmed that the effects of l-theanine are comparable to the benzodiazepine alprazolam in both efficacy and time to effect, while causing fewer adverse effects.[13]

Using a combination of evidence-based herbal therapeutics in conditions such as anxiety and depression allows us to focus on multiple therapeutic targets simultaneously. Employing this approach may confer several advantages over traditional pharmacotherapy, including the modulation and restoration of homeostatic mechanisms achieved through the pleiotropic effects of medicinal herbs, a reduction in unpleasant side effects and consequently enhanced treatment compliance. Additionally, many herbs can be used alongside conventional treatments, for enhanced outcomes.[14]

As our understanding of neurobiology and network pharmacology develops, the mechanisms by which herbal medicines work to support a healthy mood and stress response are coming to light. Accumulating evidence demonstrating the efficacy of these compounds in the form of clinical trials and meta-analyses provides additional confidence in our traditional methods and opens new horizons for effective, integrative mental health care.

For further technical data, visit Metagenics Institute

References

[1] Australian Insititute of Health and Wellness (AIHW). Mental health [Internet]. AIHW; 2020 [updated 2020 Jul 23, cited 2021 Dec 7]. Available from https://www. aihw.gov.au/reports/australias-health/mental-health

[2] Yin AQ, Wang F, Zhang X. Integrating endocannabinoid signalling in the regulation of anxiety and depression. Acta Pharmacol Sin. 2019 Mar;40(3):336-41. doi: 10.1038/s41401-018-0051-5

[3] Gold PW. The organization of the stress system and its dysregulation in depressive illness. Mol Psychiatry. 2015 Feb;20(1):32-47. doi: 10.1038/mp.2014.163

[4] Yin AQ, Wang F, Zhang X. Integrating endocannabinoid signalling in the regulation of anxiety and depression. Acta Pharmacol Sin. 2019 Mar;40(3):336-41. doi: 10.1038/s41401-018-0051

[5] Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signalling and function in the central nervous system. Int J Mol Sci. 2018 Mar 13;19(3):833. doi: 10.3390/ijms19030833

[6] Sanna MD, Les F, Lopez V, Galeotti N. Lavender (Lavandula angustifolia) essential oil alleviates neuropathic pain in mice with spared nerve injury. Front Pharmacol. 2019 May 9;10:472. doi: 10.3389/fphar.2019.00472

[7] Schmidt ME, Liebowitz MR, Stein MB, Grunfeld J, Van Hove I, Simmons WK, et al. The effects of inhibition of fatty acid amide hydrolase (FAAH) by JNJ-42165279 in social anxiety disorder: A double-blind, randomized, placebo-controlled proof-of-concept study. Neuropsychopharmacology. 2021 Apr;46(5):1004-10. doi: 10.1038/s41386-020-00888-1

[8] Woelk H, Schlafke S. A multi-centre, double-blind, randomised study of the lavender oil preparation Silexan in comparison to lorazepam for generalised anxiety disorder. Phytomed. 2010;17:94-9. doi:10.1016/j.phymed.2009.10.006

[9] Yap WS, Dolzhenko AV, Jalal Z, Hadi MA, Khan TM. Efficacy and safety of lavender essential oil (silexan) capsules among patients suffering from anxiety disorders: a network meta-analysis. Sci Rep. 2019 Dec 2;9(1):18042. doi: 10.1038/s41598-019-54529-9

[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 Jul-Aug;66(4):607-13. doi: 10.1097/01.psy.0000132877.72833.71

[11] Alijaniha F, Naseri M, Afsharypuor S, Fallahi F, Noorbala A, Mosaddegh M, et al. Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. J Ethnopharmacol. 2015 Apr 22;164:378-84. doi: 10.1016/j.jep.2015.02.007

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

[13] Williams JL, Everett JM, D'Cunha NM, Sergi D, Georgousopoulou EN, Keegan RJ, 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 Mar;75(1):12-23. doi: 10.1007/s11130-019-00771-5

[14] Garakani A, Murrough JW, Freire RC, Thom RP, Larkin K, Buono FD, et al. Pharmacotherapy of anxiety disorders: current and emerging treatment options. Front Psychiatry. 2020 Dec 23;11:595584. doi: 10.3389/fpsyt.2020.595584