Herbal Medicine: What Psychiatrists Need to Know

Psychiatric Times, Vol 39, Issue 10,

Herbal medicines have been used to treat mental health disorders since ancient times, and continue to be useful today.

SPECIAL REPORT: INTEGRATIVE MEDICINE

Herbal medicines have been used to treat mental health disorders since ancient times. Many of the medications used in contemporary medicine originated from plants—salicylic acid from the willow tree, for example, and morphine from poppies. Numerous botanical treatments are useful in general psychiatry. This article discusses the most beneficial and commonly used herbal medicines to treat mental health concerns (Table 1).

Americans spent $11.3 billion on herbal supplements in 2020, which represented a record increase in spending of 17.3% from 2019 to 2020.1 According to the 2020 COVID-19 consumer survey of the Council for Responsible Nutrition,2 among those who increased supplement intake, nearly a quarter cited mental health–related reasons, including stress and anxiety.3

US consumers are spending the most money on the following herbs with mental health applications: cannabidiol (CBD), ashwagandha (Withania somnifera), turmeric, gingko, St. John’s wort (SJW), valerian, maca, and rhodiola. Several of these herbs also have applications for physical health, such as inflammation, cardiovascular disease, and physical performance.

The research evidence and consumer spending do not align. As psychiatrists, we can help guide our patients in making beneficial choices when they choose to take herbs.

Most of the psychotropic herbal medicines available over the counter are quite safe, with fewer adverse effects than conventional antidepressants or antianxiety agents.4 Yet not all are safe. For example, SJW could cause a switch to mania in bipolar disorder5; also, it should not be taken with certain other drugs due to potential interactions.6 Kava supplements made from the incorrect plant type and incorrectly processed have caused liver toxicity.7 Thus, it is important to know which herbal agents your patient may be taking and whether herbal medications may be interacting with conventional medications.

Herbal medicines are more complex than conventional medications, which may discourage psychiatrists from recommending them. Take heart: Most herbs are quite safe. It may be easiest to select 2 or 3 herbs, to start, and learn about them in depth. Alternately, choose to learn about the herbs your patients are already using and mixing with the conventional medications we may be prescribing.

Herbs’ complexity comes from the fact that they are whole plants rather than a single chemical active ingredient in a medication. A plant’s beneficial effect may be related to complex synergistic and polyvalent interactions among many of its own components or multiple plants. A plant or herbal combination may contain multiple molecules with different physiological effects, or it may modify the absorption or metabolism of other bioactive components, or it may reduce adverse effects. For example, adding black pepper to turmeric may dramatically enhance the absorption of turmeric into the bloodstream.8 Within a single plant, valerian has several different effects including anxiolysis, muscle relaxation, and sleep promotion; notably, valerian involves a number of compounds such as free GABA; benzodiazepine receptor-binding flavonoids; terpenes, which inhibit GABA breakdown and cause smooth muscle relaxation; and lignans, which inhibit serotonin binding.

Herbal medicines may work better because of the complex and synergistic interactions, yet that strength is an obstacle to standardized research, and it may worry clinicians. Comparing the results of studies on different preparations of the same herb produced by different manufacturers may be difficult. The exact chemical composition of an herbal preparation is dependent on many factors, described in Table 2.

Research on herbal medicines is elucidating the mental health effects and underlying mechanisms of action of many individual herbs, a few of which are discussed in this article. Herbal medicines may have antidepressant, anxiolytic, sedative, hypnotic, analgesic, and cognitive-enhancing effects, in addition to “adaptogenic” effects, that increase resilience to stress. Key mechanisms of actions of herbal medicines identified in research can be found in Table 3.

St. John’s Wort (Hypericum perforatum)

The use of SJW dates back to ancient times, and it is among the most researched herbal medicines for mental health. It is a first-line treatment for depression in several European countries.

Evidence: A 2008 Cochrane meta-analysis9 of 29 trials including 5489 adult patients found significant results from 18 studies in favor of SJW versus placebo. SJW appeared equivalent to selective serotonin reuptake inhibitors (SSRIs). A 2016 review10 of 35 studies involving nearly 7000 adult patients found that SJW monotherapy for mild-to-moderate depression was superior to placebo in improving depression symptoms, and it was about equivalent in effect to antidepressants. In research studies, the dose ranged from 300 mg to 1800 mg per day. Most preparations used in research contained standardized 0.3% hypericin and 2% to 5% hyperforin.

Mechanism of Action: SJW’s likely mechanism of action involves nonselective inhibition of serotonin, dopamine, norepinephrine, GABA, and L-glutamate uptake, and decreased degradation of neurochemicals. In addition, SJW modulates cortisol levels.

Adverse Effects: SJW appears to be generally well tolerated, with adverse effects occurring in 0.1% to 5.7% of users (comparable with placebo).11 Most common adverse reactions involve reversible dermatological and gastrointestinal issues. Per the 2016 review of the 35 studies reviewed, 34 included safety data, and overall SWJ did not cause more adverse effects than placebo.

SJW is a potent inducer of CYP 3A4 and P glycoprotein, and it can lower the levels of many commonly used medications including oral contraceptives, methadone, and cyclosporine. It is best to check reference materials for possible SJW-medication interactions or even to avoid use with certain medications. Preparations that are < 4 mg of hyperforin may be safer and less likely to cause drug-herb interactions.

Rare, serious adverse effects include serotonin syndrome (when combined with an SSRI), induction to mania, and psychosis. A 2004 article reported 17 cases in the literature where SJW was associated with likely triggering mania or psychosis.12

Clinical Pearls:

- The main concern about and obstacle to SJW use is concern for drug interactions.

- In clinical practice, you may find better adherence to SJW if you recommend a specific formulation and monitor the use of SJW as you would any other medication. Increase the dose gradually from 300 mg up to a maximum 1800 mg. Monitor for adverse effects, and if there is no benefit by 6 weeks, consider adding other augmenting agents or switching to a different agent.

Turmeric (Curcuma longa)

Turmeric is a common cooking spice and a traditional Ayurvedic and Chinese medicine.

Evidence: A 2020 meta-analysis of 10 studies involving 530 participants found a significant and large effect size of curcumin for depressive symptoms based on 10 studies and on anxiety symptoms based on 5 studies.13 Curcumin was well tolerated. A meta-analysis14 of 6 trials lasting 4 to 8 weeks and involving 377 patients with depression showed turmeric’s significant benefit in reducing depressive symptoms compared with placebo. Three studies also reported significant antianxiety effects. A 6-week randomized controlled trial (RCT) of 108 male adults in China showed benefit for 1000 mg curcumin per day versus placebo as an augmentation to escitalopram.15 In addition, the study documented that curcumin decreased inflammatory cytokines (interleukin-1 beta and tumor necrosis factor alpha) and salivary cortisol, and increased brain-derived neurotrophic factor.

Mechanism of Action: Curcumin, a key component of turmeric, has anti-inflammatory, antioxidant, neuroprotective, and monoamine regulatory effects.

Clinical Pearls:

- Turmeric may be particularly useful for patients with depression and inflammation. When checking blood work, check high-sensitivity C-reactive protein, and if it is higher than 1 mg/L, consider adding turmeric to an antidepressant.

- Recommend formulations that are of high quality and contain black pepper extract to increase absorption.

Saffron (Crocus sativus)

The majority of research on saffron was conducted in Iran, where it has been used as a traditional treatment for mood for centuries. Its constituents safranal and crocin show antidepressant, anxiolytic, and hypnotic effects. Crocin may act through reuptake inhibition of dopamine and norepinephrine, and safranal via serotonin reuptake inhibitors. In addition, saffron has anti-inflammatory effects.

Evidence: A meta-analysis of 5 published high-quality RCTs showed a large effect size in favor of saffron versus placebo for depressive symptoms, and equal effect to antidepressant groups.16 In addition, a 12-week double-blind RCT (n = 60) of 50 mg per day of saffron was positive.17 However, the conducted studies were small and of short duration, and little research has been conducted at Western study sites.

Clinical Pearls:

- Look for a higher dose of saffron when selecting a supplement.

- Consider twice a day dosing.

- Saffron can be used as monotherapy or adjunctive use for mild to moderate depression.

Lavender (Lavandula angustifolia)

Lavender has been used in aromatherapy for anxiety.

Evidence: A 2021 meta-analysis of 17 articles showed significant benefit of lavender for decreasing depression symptoms.18 Nearly three-fourths of the studies in this meta-analysis were conducted in Iran, most studies involved aromatherapy, and 5 studies involved ingesting lavender. One study evaluated the effects of lavender essential oil (Silexan) on patients with mixed anxiety and depressive disorder, a condition with subsyndromal symptoms of anxiety and depression.19 In this study, 318 patients received 80 mg Silexan or placebo for 70 days. Silexan was beneficial for decreasing depression scores and improving quality of life. The main adverse effect was eructation.

Clinical Pearls:

- Select supplements with 80 mg to 160 mg of lavender essential oil per day in the form of soft gels.

- Weak evidence for monotherapy, more appropriate for adjunctive use in major depressive disorder and generalized anxiety disorder.

Cannabis (Cannabis sativa)

Another interesting herb is the cannabis plant (Cannabis sativa), which contains delta-9-tetrahydrocannabinol (THC) and CBD. Currently, despite the very high spending on these by consumers, very little research is available to guide use. A review article published in Lancet Psychiatry in 2019 of 83 studies, including 40 RCTs and 3067 participants, concluded that there is a lack of evidence that cannabinoids improve symptoms of depression, anxiety, attention-deficit/hyperactivity disorder, tics, posttraumatic stress disorder (PTSD), or psychosis.20 The single positive finding was that there was very-low-quality evidence that THC with or without CBD may help with anxiety for those who also have other medical conditions. A 2021 review noted that with only 8 very small studies at the time, there was insufficient evidence for clinicians recommending CBD or THC to manage mood disorders, anxiety, or PTSD.21 Clinically, many psychiatrists recommend CBD for anxiety and warn about the dangers of chronic THC use—yet, at this time, we do not have much research evidence to guide us.

In my clinical practice, I find that some patients find CBD without THC or with a minimal amount of THC (20:1 ratio of CBD to THC) useful for anxiety, sleep, and inflammation without significant adverse effects. The dose range of CBD is large, from approximately 5 mg to 45 mg for effect. Many patients prefer CBD in capsules for consistency of dose.

Clinical Pearls:

- Soft gel formulations of CBD at 15mg are good place to start and recommend to patients to start with one soft gel, if not effect take another one 30 min later, and another one 30 min later to determine the effective dose.

- Avoid confusion with hemp seed oil, which does not contain CBD.

- Select high quality brands or obtain through dispensaries.

Other promising herbs for the treatment of mental health disorders include ashwagandha with moderate evidence and galphimia with modest evidence for anxiety disorders. Gingko has week support for adjunctive treatment of negative symptoms in schizophrenia.22

Concluding Thoughts

Herbal medicine is an important addition to our conventional medication toolbox. Herbs are generally well tolerated and affordable. For patients interested in using herbs, we have sufficient evidence to recommend several agents discussed in this article. It is important to ask patients what herbs and supplements they take and to assess for potential drug-herb interactions and adverse effects.

Dr Lewis is a psychiatrist and psychotherapist at Mind Body Seven Psychiatry, and a clinical assistant professor at New York University.

References

1. Smith T, Majid F, Eckl V, Reynolds CM. Herbal supplement sales in US increase by record-breaking 17.3% in 2020. HerbalEGram. 2021;131:52-65.

2. Smith T. CRN consumer surveys find changes in supplement use in 2020. American Botanical Council/Herbal Medicine Institute. December 2020. Accessed August 31, 2022. https://www.herbalgram.org/resources/herbalegram/volumes/volume-17/number-12-december-2020/crn-supplement-survey/crn-supplement-survey/

3. CRN’s COVID-19 survey on dietary supplements: consumer insights on usage and attitudes about dietary supplements in light of the coronavirus pandemic. Council for Responsible Nutrition. Accessed August 31, 2022. https://www.crnusa.org/COVID19survey

4. 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):841-860.

5. Fahmi M, Huang C, Schweitzer I. A case of mania induced by hypericum. World J Biol Psychiatry. 2002;3(1):58-59.

6. Madabushi R, Frank B, Drewelow B, et al. Hyperforin in St. John’s wort drug interactions. Eur J Clin Pharmacol. 2006;62(3):225-233.

7. Teschke R. Kava hepatotoxicity—a clinical review. Ann Hepatol. 2010;9(3):251-265.

8. Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J. 2013;15(1):195-218.

9. Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database Syst Rev. 2008;2008(4):CD000448.

10. Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John’s wort for major depressive disorder. Syst Rev. 2016;5(1):148.

11. Knüppel L, Linde K. Adverse effects of St. John’s Wort. J Clin Psychiatry. 2004;65(11):1470-1479.

12. Stevinson C, Ernst E. Can St. John’s wort trigger psychoses? Int J Clin Pharmacol Ther. 2004;42(9):473-480.

13. Fusar-Poli L, Vozza L, Gabbiadini A, et al. Curcumin for depression: a meta-analysis. Crit Rev Food Sci Nutr. 2020;60(15):2643-2653.

14. Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical use of curcumin in depression: a meta-analysis. J Am Med Dir Assoc. 2017;18(6):503-508.

15. Yu J-J, Pei L-B, Zhang Y, et al. Chronic supplementation of curcumin enhances the efficacy of antidepressants in major depressive disorder: a randomized, double-blind, placebo-controlled pilot study. J Clin Psychopharmacol. 2015;35(4):406-410.

16. Hausenblas HA, Saha D, Dubyak PJ, Anton SD. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med. 2013;11(6):377-383.

17. Mazidi M, Shemshian M, Mousavi SH, et al. A double-blind, randomized and placebo-controlled trial of saffron (Crocus sativus L.) in the treatment of anxiety and depression. J Complement Integr Med. 2016;13(2):195-199.

18. Firoozeei TS, Feizi A, Rezaeizadeh H, et al. The antidepressant effects of lavender (Lavandula angustifolia Mill.): a systematic review and meta-analysis of randomized controlled clinical trials. Complement Ther Med. 2021;59:102679.

19. Kasper S, Volz H-P, Dienel A, Schläfke S. Efficacy of Silexan in mixed anxiety-depression—a randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2016;26(2):331-340.

20. Black N, Stockings E, Campbell G, et al. Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis. Lancet Psychiatry. 2019;6(12):995-1010.

21. Stanciu CN, Brunette MF, Teja N, Budney AJ. Evidence for use of cannabinoids in mood disorders, anxiety disorders, and PTSD: a systematic review. Psychiatr Serv. 2021;72(4):429-436.

22. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. World J Biol Psychiatry. 2022;1-32.