St. John's Wort

botanical
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St. John's Wort (Hypericum perforatum) is a flowering plant with a long history of use in traditional medicine. Its primary active compounds, hypericin and hyperforin, are thought to contribute to its potential role in addressing mood imbalances, specifically mild to moderate depressive symptoms. It is also considered for related anxiety or sleep concerns. The mechanism involves modulating neurotransmitter levels in the brain. It is suggested to inhibit the reuptake of several neurotransmitters, including serotonin, dopamine, and norepinephrine, which increases their availability in the synaptic cleft. This action is similar to some antidepressants, although the exact pathways and extent of action differ. Beyond mood support, St. John's Wort has been traditionally used topically for skin conditions, wounds, and burns due to potential anti-inflammatory and antiseptic properties. However, its internal use for mood is the most studied application. Caution is necessary due to its significant potential for drug interactions.

Natural sources
Native to Europe, western Asia, and northern AfricaMeadowsClearingsRoadsides

Ingredient forms

No public comparison lists found.

Timing & Intake
AnytimeWith food
This is often taken in divided doses throughout the day. Taking it with food may help minimize potential stomach discomfort.
Optimal Dosage
Minimum300 mg
Maximum900 mg
Safety & Toxicity
5 safety notes
  • May significantly interact with numerous medications, including antidepressants, birth control, blood thinners, and immunosuppressants. Consult a healthcare professional before use, especially if on medication.
  • Avoid excessive sun exposure and use sun protection due to increased photosensitivity.
  • Not recommended for severe depression, bipolar disorder, or in children and pregnant/breastfeeding individuals without medical supervision.
  • Discontinue use and seek medical attention if symptoms of serotonin syndrome (e.g., agitation, confusion, rapid heart rate, muscle rigidity) occur, especially when combined with other serotonergic substances.
  • Should not be stopped abruptly; consult a healthcare professional for guidance on tapering.
Goals
Mood Support
Mood Support
Impact
Moderate effect
Typical dose:300–900 mg
The active compounds, hypericin and hyperforin, are thought to inhibit the reuptake of key neurotransmitters, increasing their availability in the brain. It has significant potential for drug interactions and should be used with medical guidance.

Study evidence

97 studies

St. John's Wort has evidence for reducing symptoms of mild to moderate major depression, although results vary across trials and extracts. This does not establish a general mood boost in people without depression, and its potential to interfere with other medicines is a meaningful limitation.

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Stress Relief
Stress Relief
Impact
Situational effect
Typical dose:300–900 mg
St. John's Wort works by influencing neurotransmitters like serotonin, dopamine, and norepinephrine. It is effective for lifting mood when stress manifests as depressive symptoms, but must be used with caution due to significant interactions with many prescription medications, making it situationally appropriate.

Study evidence

6 studies

St. John’s wort may ease anxiety symptoms that accompany depression, but the supplied evidence does not establish it as a treatment for everyday stress. Reviews find insufficient support for its use alone against anxiety, and controlled results are not consistently positive.

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Studies

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Sources

Up to five highest-ranked published examples per goal. Study counts and charts include all published studies for the connection.

  1. St John's wort for major depression.
    Linde K; Berner MM; Kriston L · The Cochrane database of systematic reviews · 2009
    Systematic review5,489 participants29 studies pooledMood Support
  2. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial.
    Lecrubier Y; Clerc G; Didi R; Kieser M · The American journal of psychiatry · 2002
    Randomized trial375 participantsMood Support
  3. A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review.
    Whiskey E; Werneke U; Taylor D · International clinical psychopharmacology · 2002
    Meta-analysis22 studies pooledMood Support
  4. Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial.
    Kalb R; Trautmann-Sponsel RD; Kieser M · Pharmacopsychiatry · 2001
    Randomized trial72 participantsMood Support
  5. Complementary therapies for clinical depression: an overview of systematic reviews.
    Haller H; Anheyer D; Cramer H; Dobos G · BMJ open · 2020
    Systematic review26 studies pooledMood Support
  6. Comparison of St John's wort and imipramine for treating depression: randomised controlled trial.
    Woelk H · BMJ (Clinical research ed.) · 2000
    Randomized trial324 participantsStress Relief
  7. Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F 32.1) with St. John's wort.
    Friede M; Henneicke von Zepelin HH; Freudenstein J · Pharmacopsychiatry · 2002
    Randomized trial240 participantsStress Relief
  8. Kava and St. John's Wort: current evidence for use in mood and anxiety disorders.
    Sarris J; Kavanagh DJ · Journal of alternative and complementary medicine (New York, N.Y.) · 2009
    Systematic reviewStress Relief
  9. Do early changes in the HAM-D-17 anxiety/somatization factor items affect the treatment outcome among depressed outpatients? Comparison of two controlled trials of St John's wort (Hypericum perforatum) versus a SSRI.
    Bitran S; Farabaugh AH; Ameral VE; LaRocca RA; Clain AJ; Fava M; Mischoulon D · International clinical psychopharmacology · 2012
    Other475 participantsStress Relief
  10. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review.
    Lakhan SE; Vieira KF · Nutrition journal · 2011
    Systematic review2,619 participants24 studies pooledStress Relief