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St. John's Wort

Mild to moderate depression

herb
Evidence · Grade ASafety · Use with caution
Human trial evidenceTraditional useSafety cautionInteraction risk

Flowering herb with RCT evidence comparable to SSRIs for mild-to-moderate depression.

St. John's Wort (Hypericum perforatum) is a flowering plant that has been traditionally used for various health conditions. In modern contexts, it is most recognized for its potential role in addressing symptoms of mild to moderate depression. Its use has been the subject of numerous studies, though the exact mechanisms by which it exerts its effects are still being investigated. It is available in various forms, including capsules, teas, and tinctures. While some research suggests benefits for mood, it is important to note that St. John's Wort can interact significantly with many prescription medications. Due to these potential interactions and the need for careful medical supervision, individuals considering its use, especially for depression, should consult with a healthcare professional.

Quick answer

What it is: St.

May support:OCD, PMDD, Seasonal Affective Disorder, PMS, Anxiety Disorder, Menopause, Panic Disorder, Depression

Evidence:Evidence · Grade A

Safety:Safety · Use with caution

Evidence Summary

Evidence · Grade A

The current understanding of St. John's Wort's efficacy for mild to moderate depression is based on a body of clinical trials. However, without specific studies provided, a detailed rationale for a specific evidence grade cannot be given. Generally, meta-analyses and systematic reviews have been conducted, comparing St. John's Wort to placebo and conventional antidepressants.

Last reviewed · Jun 2026

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Commonly Combined With

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Why It Works

Inhibits reuptake of serotonin, dopamine, and norepinephrine; modulates HPA axis.

How it works in more detail

St. John's Wort is believed to exert its effects through a complex interplay of several active compounds, including hypericin, hyperforin, and flavonoids. Hyperforin is thought to be a primary contributor to its antidepressant activity, potentially by inhibiting the reuptake of neurotransmitters such as serotonin, norepinephrine, and dopamine, thereby increasing their availability in the synaptic cleft. Hypericin may also play a role, possibly by modulating neurotransmitter receptors or inhibiting monoamine oxidase (MAO). The combined action of these compounds may lead to mood-stabilizing effects.

How to use

Always consult a qualified clinician.

Editorial guidance

Suggested dosage
300 mg standardized extract (0.3% hypericin) 3x daily
Research dosage range
Commonly studied dosages for depression range from 300 mg to 900 mg of extract per day, often standardized to hypericin or hyperforin content, typically divided into two or three doses.
Typical onset
2–4 weeks
Typical forms
Capsule, Tablet, Tincture, Tea
Quality markers
Look for products standardized to a specific percentage of active compounds, such as hypericin (e.g., 0.3%) or hyperforin (e.g., 3-5%). Reputable brands that provide third-party testing for purity and potency are advisable.
Medication interactions
  • Antidepressants (SSRIs, SNRIs, MAOIs, tricyclics)
  • Oral contraceptives
  • Anticoagulants (blood thinners)
  • Immunosuppressants
  • Antiretrovirals (HIV/AIDS medications)
  • Digoxin
  • Chemotherapy drugs
  • Triptans (for migraines)
  • Theophylline
Avoid if
  • Pregnant or breastfeeding
  • Taking antidepressant medications (SSRIs, SNRIs, MAOIs, tricyclics)
  • Taking oral contraceptives
  • Taking blood thinners (e.g., warfarin)
  • Taking immunosuppressants (e.g., cyclosporine)
  • Taking medications for HIV/AIDS (e.g., protease inhibitors, NNRTIs)
  • Taking digoxin
  • Diagnosed with severe depression or bipolar disorder
  • Undergoing surgery (discontinue prior to surgery)

Community tips

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Suggested dosage

300 mg standardized extract (0.3% hypericin) 3x daily

General guidance — discuss specifics with a clinician.

Active medicinal compounds

Hypericin, Hyperforin, Flavonoids (e.g., hyperoside, quercitrin, rutin), Biflavonoids, Proanthocyanidins.

Traditional use

Historically, St. John's Wort has been used in traditional European medicine for a variety of conditions, including nerve pain, anxiety, and wound healing. Its use for 'melancholy' or mood disturbances dates back centuries, predating modern scientific investigation.

Safety

Safety warnings

St. John's Wort can cause significant interactions with a wide range of prescription medications, including antidepressants, oral contraceptives, blood thinners, and immunosuppressants, potentially reducing their effectiveness or increasing side effects. It may also increase sensitivity to sunlight. Consultation with a healthcare professional is crucial before use.

Avoid if

  • Pregnant or breastfeeding
  • Taking antidepressant medications (SSRIs, SNRIs, MAOIs, tricyclics)
  • Taking oral contraceptives
  • Taking blood thinners (e.g., warfarin)
  • Taking immunosuppressants (e.g., cyclosporine)
  • Taking medications for HIV/AIDS (e.g., protease inhibitors, NNRTIs)
  • Taking digoxin
  • Diagnosed with severe depression or bipolar disorder
  • Undergoing surgery (discontinue prior to surgery)

Medication interactions

  • Antidepressants (SSRIs, SNRIs, MAOIs, tricyclics)
  • Oral contraceptives
  • Anticoagulants (blood thinners)
  • Immunosuppressants
  • Antiretrovirals (HIV/AIDS medications)
  • Digoxin
  • Chemotherapy drugs
  • Triptans (for migraines)
  • Theophylline

Reported side effects

  • Photosensitivity (increased sensitivity to sunlight)
  • Gastrointestinal upset (e.g., nausea, stomach ache)
  • Dizziness
  • Fatigue
  • Dry mouth
  • Restlessness
  • Headache

General guidance — discuss specifics with a clinician.

Evidence ecosystem

Scientific literature, clinical guidance, government sources, ongoing research, traditional use, and lived experience — grouped by source type and quality.

Overall grade (A)

The current understanding of St. John's Wort's efficacy for mild to moderate depression is based on a body of clinical trials. However, without specific studies provided, a detailed rationale for a specific evidence grade cannot be given. Generally, meta-analyses and systematic reviews have been conducted, comparing St. John's Wort to placebo and conventional antidepressants.

Filter by source type

Observational Studies(6)

Cohort, case-control, and cross-sectional human studies.

Moderate Quality

  • Herbal medicine for treating psoriasis: A systematic review.

    Anheyer M, Cramer H, Ostermann T, Längler A, Anheyer D · Complementary therapies in medicine · 2025 · n=1115

    Psoriasis, a chronic skin condition influenced by both genetic and environmental factors, affects approximately 2 % of the global population. Treatment approaches range from topical agents for mild to moderate cases to systemic therapies for moderate to severe forms. Complementary and integrative medicine, including herbal remedies, is increasingly utilized by psoriasis patients, with herbal medicine being the most prevalent choice. This systematic review adhered to PRISMA guidelines and Cochrane recommendations, with prior registration. Searches were conducted in Medline/PubMed, Scopus, and the Cochrane Central Register of Controlled Trials through June 2024. Inclusion criteria encompassed randomized controlled trials (RCTs) evaluating herbal therapies in psoriasis patients of any age. Data extraction and risk of bias assessment were performed independently by two authors, with discrepancies resolved through discussion. A total of 20 RCTs involving 1115 patients were included

    Observational StudyPubMedLow Quality

  • Complementary therapies for clinical depression: an overview of systematic reviews.

    Haller H, Anheyer D, Cramer H, Dobos G · BMJ open · 2019

    As clinical practice guidelines vary widely in their search strategies and recommendations of complementary and alternative medicine (CAM) for depression, this overview aimed at systematically summarising the level 1 evidence on CAM for patients with a clinical diagnosis of depression. PubMed, PsycInfo and Central were searched for meta-analyses of randomised controlled clinical trials (RCTs) until 30 June 2018. Outcomes included depression severity, response, remission, relapse and adverse events. The quality of evidence was assessed according to Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) considering the methodological quality of the RCTs and meta-analyses, inconsistency, indirectness, imprecision of the evidence and the potential risk of publication bias. The literature search revealed 26 meta-analyses conducted between 2002 and 2018 on 1-49 RCTs in major, minor and seasonal depression. In patients with mild to moderate major depression, moderate qual

    Observational StudyPubMedLow Quality

  • Herbal drug treatment.

    Jarema M · Neuro endocrinology letters · 2008

    Herbal drug treatment has been known for centuries as a part of traditional medicine. Nowadays, it is still considered a useful and natural way to treat several medical conditions, including mental disturbances. The most frequently treated mental conditions include mood disorders (mainly depression), anxiety disorders, somatoform disorders, age-related cognitive decline, and sometimes psychotic disorders. Some herbal formulations, such as St. John's wort, have been analyzed in clinical trials to estimate their real value. The use of other herbal medicines, such as Kava-kava, valerian, and Ginkgo biloba is discussed.

    Observational StudyPubMedLow Quality

Clinical Trial Registries(1)

Registered ongoing or completed trials (ClinicalTrials.gov).

Moderate Quality

Limitations: A key limitation of the current evidence, without specific studies, is the variability in study design, St. John's Wort preparations, and dosages used. Publication bias may also be a factor. Furthermore, most research focuses on mild to moderate depression, with less robust evidence for severe depression.

This page is educational. Statements use phrases like "may support" and "has been studied for"because no remedy here is approved to cure, treat, or reverse any condition. Discussion happens on the ailment pages — community statistics here are derived from those reports. Always consult a qualified clinician.

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