Anti-anxiety and anti-stress phytomedicines

Researchers are probing mechanisms of action and documenting therapeutic applications of herbal formulas, for example Japanese Kampo, Indian Ayurveda, traditional Chinese medicine, traditional Tibetan (Sowa-Rigpa), Iranian (tebbe sonnati-e irāni) and African medicine (yorùbá or egbo'gi), Aboriginal medicine, medicines of native tribes of the Americas and European herbal medicines.

The most powerful, well-studied anti-stress herbs are the adaptogens and their extracts, which have been shown to increase the ability of organisms to tolerate, survive and perform under a wide range of stressors, including physical, psychological, chemical, toxic, infectious, carcinogenic, hypoxic and thermal stresses, radiation and exhaustion: Rhodiola rosea, Panax ginseng, Schisandra chinensis, Siberian ginseng (Eleutherococcus senticosus) and ashwagandha (Withania somnifera). Other herbs with some adaptogenic properties include: maca (Lepidium meyenii), saffron (Crocus sativus) and maral root (Rhaponticum carthamoides). Genomic studies reveal up- and downregulation of hundreds of genes by adaptogenic herbs such as R. rosea, with changes in activation patterns when herbs are combined, as in formulas containing R. rosea, E. senticosus, and S. chinensis (Brown Reference Brown, Gerbarg and Muskin2009a; Gerbarg Reference Gerbarg, Muskin and Brown2017).

Reviews of randomised controlled trials (RCTs) found significant benefits with: rhodiola or arctic root (Rhodiola rosea, 8 RCTs, stress, anxiety, depression, fatigue, energy, cognitive function), ginkgo (Ginkgo biloba, 9 RCTs, energy, cognitive function), brahmi (Bacopa monnieri, 6 RCTs, cognitive function), saffron (Crocus sativa, 12 RCTs, anxiety and depression), kava (Piper methysticum, 5 RCTs, short-term use for anxiety, has misuse potential), ashwagandha (Withania somniferum, moderate benefits for stress), kanna (Sceletium tortuosum, connectivity study showed reduced amygdala–hypothalamus coupling), sage (Salvia officianalis, mild effects for insomnia), lemon balm (Melissa officinalis, mild effects for anxiety and insomnia), passionflower (Passiflora incarnata, 6 RCTs, mild acute effects for anxiety), chamomile (Matricaria recutita, mild effects on insomnia), lavender (Lavendula angustifolia, weak effects for anxiety and insomnia), valerian (Valeriana officinalis, mild effects on anxiety, insomnia) (Brown Reference Brown, Gerbarg and Muskin2009a; Gerbarg Reference Gerbarg, Muskin and Brown2017; Yeung Reference Yeung, Hernandez and Mao2018; Mendelson Reference Mendelson2020).

Although the reviews of clinical trials of phytomedicinals noted above included only RCTs, there is heterogeneity in the quality of the trials and limitations related to the number of participants, masking and researcher alliance. The cited reviews address these issues in more detail.

A common misconception among reviewers of herbal studies is that in vitro effects on cytochrome P450 isozymes translate into increased risks for herb–drug interactions in humans (in vivo). This is often not the case because digestion and metabolism convert herbal constituents into secondary metabolites, which may be completely benign or have opposite effects to those of whole extracts in vitro (Gerbarg Reference Gerbarg, Muskin and Brown2017).

The quality and potency of herbal extracts is critical for efficacy. Resources for assessing supplement quality are listed in Box 1.

Mind–body methods, attentional focus, interoception and awareness for stress reduction

Clinical studies with modern research methodologies are revealing the underlying mechanisms by which mind–body techniques can improve psychophysiological states in stress-related mental and physical disorders. Convergent evidence indicates rapid relief of anxiety and stress using voluntarily regulated breathing techniques (e.g. coherent breathing and pranayama), enhanced by movement (e.g. qigong and tai chi), postures (e.g. yoga asanas), attentional focus, interoceptive awareness (the perception of sensations arising from inside the body), visualisation and meditation. Knowledge gained from biological markers of stress (e.g. cortisol, oxidative stress), brain imaging, electroencephalography, neurotransmitter levels, neurohormone tests and psychological measures is being used to improve the efficacy of mind–body programmes (Brown Reference Brown and Gerbarg2009b; Gerbarg Reference Gerbarg, Muskin and Brown2017, Reference Gerbarg, Mason, Mason and Birch2018). Key mechanisms of action supported by human studies indicate: reduction of overactivity of the sympathetic nervous system and activation of the vagal parasympathetic system and gamma-aminobutyric acid (GABA) transmission, increased heart rate variability and brainwave entrainment. These mechanisms are associated with and can improve attention, cognitive function, long-term potentiation, emotion regulation, compassion and neuroplasticity, as well as inflammation, anxiety, depression, pain and insomnia (Gerbarg Reference Gerbarg, Muskin and Brown2017, Reference Gerbarg, Mason, Mason and Birch2018; Porges Reference Porges, Carter, Gerbarg, Muskin and Brown2017).

Other modalities

Robust data support the use of acupuncture for pain management. A meta-analysis concluded that acupuncture is effective for chronic musculoskeletal pain, headache and osteoarthritic pain (Vickers Reference Vickers, Verstosick and Lewith2018). The beneficial effects of acupuncture persisted over time and could not be attributed to a placebo effect. Reviews find evidence that acupuncture is moderately beneficial for anxiety and mood disorders (Bazzan Reference Bazzan, Zabrecky and Monti2014).

Although the evidence base is not as robust, other modalities supported by clinical trials showing stress reduction include music, active drumming, singing, visualisation, imagery, aromatherapy and being in nature (ecotherapy). Most of our 300 000 years of hominid evolution occurred in small, tightly knit groups living in natural settings. It has been argued that the dissonance caused by living in urban environments contributes to stress states. Studies of shinrin-yoku (forest bathing) found indicators of reduced stress levels, including salivary cortisol, heart rate variability-related sympathetic and parasympathetic nervous system activity, blood pressure and pulse rate (Hanson Reference Hanson, Jones and Tocchini2017).

Lifestyle and nutrition

Unhealthy lifestyles and eating habits contribute to stress-related disorders. Conversely, stress and depression can exacerbate poor eating and sedentary behaviour. Diets high in sugar, saturated fats, red meats and processed foods, especially in children, have been associated with poorer mental health. In contrast, studies of the Mediterranean diet, which encourages more fresh fruits, vegetables, nuts and whole grains, show beneficial effects on depression and stress biomarkers. However, large-scale studies are still needed to assess the potential effects of specific diets on the severity of stress-related illnesses.

Mechanisms proposed to explain how diet can affect anxiety and mood include: deficiencies of vitamins and nutrients that are essential to sustain brain functions; blood sugar fluctuations; and effects on the microbiome (gut bacteria) that influence absorption of nutrients as well as inflammation (which is associated with depression) (Sarris Reference Sarris, Logan and Akbaraly2015).

Substantial evidence indicates that supplemental nutrients, used alone or in combination, could support biochemical pathways involved in antioxidant and anti-inflammatory defence, mitochondrial support, neurotransmission, stress response and mood disorders. Well-studied nutrients include: S-adenosyl methionine (SAMe), N-acetyl cysteine (NAC), acetyl-L-carnitine (ALCAR), zinc, B vitamins, folic acid, vitamin D and omega-3 fatty acids (Bottiglieri Reference Bottiglieri, Gerbarg, Brown, Gerbarg, Muskin and Brown2017; Massoumi Reference Massoumi, Gerbarg, Muskin and Roberts2019).

Summary

Interest in non-Western approaches to stress reduction is rapidly growing, driven by the urgent need for safe, lower-cost, effective care for people burdened by the everyday pressures of modern life as well as for the millions affected by disasters, wars and displacement. Quality research and field trials are needed to understand, improve and integrate ancient healing techniques into the modern practice of medicine.