Herbal remedies are more popular than ever, but how effective are they when it comes to supporting mental health?
Welcome to Weekly Education Talks with Rivia Mind, where our expert providers break down the latest treatments, research, and questions in the world of mental health care. In this three-part series, we’re taking a closer look at how herbal supplements are being used — and studied — to support three common mental health concerns: depression, anxiety, and insomnia.
Around 38% of adults and 12% of children in the U.S. report using herbal remedies1, adding up to more than $34 billion in out-of-pocket spending each year. Clearly, interest in natural approaches to mental health is high, but does that interest align with evidence?
In this first installment, we’ll discuss depression — a condition that affects hundreds of millions globally2 and often leads people to explore complementary or alternative options. Countless herbal supplements are marketed for mood support, but their effectiveness, safety, and role in treatment remain open questions.
We’ll explore:
- What the research says about commonly used herbs for depression
- How these supplements may work in the brain and body
- What dosages are typically studied
- What side effects or risks to watch for, including interactions with medications
Whether you’re curious about alternative treatments or supporting someone exploring their options, this overview offers a clear, evidence-informed look at the potential and limitations of herbal remedies for depression.
St. John’s Wort for Depression: Does It Work and Is It Safe?
St. John’s wort is one of the most researched and widely used options when it comes to herbal treatments for depression, particularly mild disorders. This flowering plant has been used for centuries in traditional medicine and remains a focus of scientific study today.
There are more than 40 clinical trials evaluating St. John’s wort for depression. Among the most comprehensive is a Cochrane Review analyzing 29 trials and data from over 5,400 participants. The findings showed that St. John’s wort was:
- More effective than placebo
- Comparable to standard antidepressants and SSRIs for mild depression
- Better tolerated, with fewer and milder side effects
However, for people with moderate to severe depression, traditional antidepressants (like SSRIs) were more effective. In these cases, St. John’s wort may not provide adequate support.
How It Works
St. John’s wort contains more than 150 active compounds, some of which may influence brain chemistry. It appears to:
- Affect the HPA (hypothalamic-pituitary-adrenal) axis, helping regulate stress hormones like cortisol
- Influence serotonin receptors
- Inhibit the reuptake of neurotransmitters, possibly improving mood3
Safety Considerations
- Birth control pills
- Certain immunosuppressants (e.g., cyclosporine)
- Heart medications (e.g., digoxin)
- Pain medications (e.g., oxycodone)
- HIV medications (e.g., indinavir)
- Chemotherapy drugs (e.g., irinotecan)
- Blood thinners (e.g., warfarin)
Typical Dosage
300–1,800 mg daily, divided into three doses. At least 900 mg per day is usually needed for a therapeutic effect.
Common Side Effects
- Dry mouth
- Dizziness
- Constipation
Less Common Side Effects
- Increased sensitivity to sunlight (phototoxicity)
- Risk of mood cycling into mania, especially in people with bipolar disorder
The Bottom Line
St. John’s wort has strong evidence supporting its use for mild depression, with effectiveness similar to some antidepressants and generally fewer side effects. However, it’s not appropriate for moderate to severe depression, and it carries significant drug interaction risks.
If you’re considering it, always consult a healthcare provider first, especially if you’re taking other medications.
S-Adenosyl Methionine (SAMe) for Depression: A Promising Supplement Backed by Science
SAMe (short for S-Adenosyl Methionine) is a naturally occurring compound found in the body. It plays a critical role in folate and B12 metabolism, and helps regulate several key neurotransmitters, including serotonin, dopamine, and acetylcholine — chemicals that are deeply connected to mood, energy, and emotional balance.
SAMe has emerged as one of the more well-researched options for depression. It’s available in several forms, including oral tablets, intramuscular (IM) injections, and intravenous (IV) administration.
More than 50 clinical trials have explored SAMe’s potential for treating depressive disorders. These include 19 randomized controlled trials and 21 studies comparing it to antidepressants, mainly a class of medications known as tricyclic antidepressants (TCAs).
While the majority of studies show promising results, one larger trial comparing SAMe with an SSRI (Lexapro) found no significant differences between the supplement, the medication, or placebo. Even so, this remains an outlier in an otherwise encouraging body of research.
In a major meta-analysis, SAMe was shown to be more effective than placebo. Participants saw a 5–6 point decrease on the Hamilton Depression Rating Scale (HAM-D), a tool clinicians use to measure the severity of depression. For context:
- Scores of 8–16 indicate mild depression
- 17–23 suggests moderate depression
- 24 or above typically reflects severe depression
SAMe has also been studied as an augmentation strategy — meaning it’s added to an existing antidepressant regimen when symptoms haven’t improved. One study followed 73 patients with treatment-resistant depression who were randomized to receive SAMe (800 mg twice daily) or placebo. Those taking SAMe reported significantly more improvement than the control group, offering hope for patients who haven’t responded to other interventions.
For some, SAMe may begin working more quickly than traditional antidepressants, with symptom relief reported within two weeks. There’s also potential benefit for individuals with MTHFR deficiency, a genetic condition that impacts folate processing. Because SAMe bypasses certain steps in folate metabolism, it may offer a more direct path to therapeutic benefit for these individuals.
Safety Considerations
According to the Mayo Clinic, SAMe may interact with several medications and supplements, especially those that influence serotonin levels. These combinations can increase the risk of serotonin syndrome, a potentially serious condition caused by too much serotonin in the body.5
Medications and substances to be cautious with include:
- Antidepressants, particularly SSRIs, SNRIs, and MAOIs. Taking SAMe alongside these drugs can raise serotonin to dangerous levels and should be avoided unless under medical supervision.
- Antipsychotic medications, which may also contribute to excess serotonin when combined with SAMe.
- Stimulants, including amphetamines, can increase the risk of serotonin overload when taken with SAMe.
- Dextromethorphan, a common ingredient in over-the-counter cough medicine, can heighten serotonin levels when combined with SAMe.
- Levodopa (Inbrija), a medication used in Parkinson’s disease treatment, may become less effective when taken with SAMe.
- Opioid medications such as tramadol (Ultram, ConZip) and meperidine (Demerol) may also raise the risk of serotonin syndrome when used with SAMe.
- St. John’s wort, another supplement that affects serotonin, can compound the effects of SAMe and increase the potential for adverse reactions.
Possible Side Effects
SAMe is well tolerated by most people, and when side effects do occur, they tend to be mild. However, like any supplement that impacts brain chemistry, it’s not without risks, especially in certain populations.
Common side effects may include:
- Digestive upset, such as nausea, diarrhea, or constipation
- Mild insomnia or difficulty falling asleep
- Dizziness
- Irritability or restlessness
- Anxiety or jitteriness
- Increased sweating
Special Precautions
Bipolar disorder: SAMe may trigger or worsen manic symptoms in people with bipolar disorder. If you have a history of mania or hypomania, do not take SAMe without consulting your provider.
Weakened immune system: Individuals with compromised immunity should speak with a healthcare provider before starting SAMe. There’s some evidence suggesting it may promote the growth of Pneumocystis, a microorganism that can cause serious infections in immunocompromised individuals.
The Bottom Line
SAMe is a well-studied supplement that plays a meaningful role in supporting neurotransmitter activity. It shows strong potential for treating mild to moderate depression, has performed better than placebo in clinical trials, and may be useful alongside conventional antidepressants when symptoms persist. People with folate processing challenges, such as MTHFR deficiency, may also benefit.
Ginkgo Biloba and Depression: A Niche but Noteworthy Role
While ginkgo biloba is more commonly associated with cognitive health and memory, emerging research suggests it may have a supportive role in managing certain symptoms related to depression, particularly one of the more frustrating side effects of antidepressant treatment: sexual dysfunction.
Ginkgo biloba is derived from the leaves of the ginkgo tree, one of the oldest living tree species on Earth. Its therapeutic potential comes from a variety of active compounds that influence blood flow and neurotransmitter function.
One open-label study looked at 63 patients who were experiencing sexual side effects from antidepressants. Participants took ginkgo biloba at doses ranging from 60 to 180 mg twice daily. The results were encouraging:
- 91% of women and 76% of men reported improvements across all phases of the sexual response cycle.
Researchers believe ginkgo’s effects may come from several mechanisms, including enhanced blood circulation, modulation of prostaglandins (which influence inflammation and vascular tone), and interactions with serotonin and norepinephrine pathways — systems that are often impacted by both depression and its treatment.
Typical Dosage
120–240 mg per day, taken in divided doses two to three times daily.
Potential Side Effects
- Mild gastrointestinal discomfort
- Headache
- Irritability
- Dizziness
- Increased bleeding risk, particularly for individuals with bleeding disorders or those taking anticoagulants
The Bottom Line:
Ginkgo biloba isn’t considered a primary treatment for depression, but it may offer meaningful support in reducing antidepressant-induced sexual dysfunction, a side effect that can impact adherence to treatment and overall quality of life. As with any supplement, it’s important to consult with a healthcare provider before adding ginkgo to your regimen, especially if you’re taking blood thinners or have a bleeding disorder.
What the Future Holds for Herbal Remedies in Depression Care
Certain herbal supplements show real promise in the treatment of mild to moderate depression, especially for those seeking alternatives to conventional medication or looking to enhance an existing treatment plan. While many studies are encouraging, it’s important to remember that these remedies aren’t without risks, especially when it comes to drug interactions and inconsistent product quality.
Most research has focused on short-term use, mild symptoms, or supplementing standard care. For people with more severe or treatment-resistant depression, evidence continues to support conventional therapies as the first line of treatment.
Still, the growing interest in natural approaches is worth noting — and studying. With more high-quality research and better regulation, herbal remedies may someday hold a more clearly defined role in clinical practice.
Until then, the safest and most effective approach is one grounded in collaboration with your provider, who can help you weigh the risks and benefits based on your unique needs.
This article is Part 1 of our series on herbal support for mental health. Next, we’ll explore the evidence around supplements used for anxiety — another area where curiosity is high and research is evolving.
Searching for depression support? Reach out today to learn more about how we can help.
Sources:
- National Health Interview Survey
- World Health Organization. Depressive disorder (depression). Published 2023. Accessed 2025.
- Nutt DJ. Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry. 2008;69 Suppl E1:4-7. PMID: 18494537.
- National Center for Complementary and Integrative Health. St. John’s Wort and Depression: In Depth. Updated 2017. Accessed 2025.
- Mayo Clinic. SamE. Published 2023. Accessed 2025.
References:
Castelein, D. Steel, A., Bowman, D., Lauche, R., & Wardle, J. (2019). A naturalistic study of herbal medicine for self-reported depression and/or anxiety a protocol. Integrative medicine research, 8(2). 123-128. https://doi.org/10.1016/j.imr.2019.04.007
Liu, L., Liu, C. Wang, Y. Wang, P., Li, Y.., & Li, B. (2015). Herbal Medicine for Anxiety, Depression and Insomnia. Current neuropharmacology, 13(4), 481-493. https://doi.org/10.2174/1570159×1304150831122734
Liu, Y. R., Jiang, Y. L.. Huang, R. Q.. Yang, J. Y., Xiao, B. K., & Dong, J. X. (2014). Hypericum perforatum L. preparations for menopause: a meta-analysis of efficacy and safety. Climacteric: the journal of the International Menopause Society, 17(4), 325-335. https://doi.org/10.3109/13697137.2013.861814
Mischoulon D. (2018). Popular Herbal and Natural Remedies Used in Psychiatry. Focus (American Psychiatric Publishing), 16(1), 2-11. https://doi.org/10.1176/appi.focus.20170041
