St. Johns Wort
Specifically for Depression
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Why it works for Depression:
Active constituents: St. John’s wort extracts contain several biologically active compounds, chiefly hyperforin and hypericin, plus flavonoids and other polyphenols. Modern pharmacology points to hyperforin as the main antidepressant-active constituent. Puget Sound Webspace
How it appears to work: hyperforin acts as a broad-spectrum reuptake inhibitor — it reduces neuronal reuptake of serotonin, norepinephrine and dopamine (and also modulates GABA and glutamate uptake), increasing their levels in the synaptic cleft. Other actions (receptor effects, anti-inflammatory and neuroprotective effects) have also been described. In short: it affects monoamine neurotransmission in ways similar to (but not identical with) some conventional antidepressants. ScienceDirect
How to use for Depression:
Typical clinical regimen used in trials and recommended in clinical summaries:
- Usual adult dose: 300 mg of a standardized extract (commonly standardized to ~0.2–0.3% hypericin or 3–6% hyperforin) taken three times daily (total ~900 mg/day). Trials used 6–12 weeks for initial assessment; some trials used higher doses (up to 1,200–1,800 mg/day) in more severe cases but that’s less common. Drugs.com
- When to expect benefit: many people (and trials) report measurable improvement after 2–4 weeks, with trials usually running 6–12 weeks; clinicians typically reassess at ~6–8 weeks. WebMD
- Product selection: choose standardized extracts (labels listing hypericin and/or hyperforin content). Because supplement regulation varies, prefer products with third-party testing (USP, NSF, ConsumerLab) where available. Drugs.com
- Switching / stopping: do not combine St. John’s wort with prescription antidepressants (SSRIs, SNRIs, MAOIs) because of serotonin-syndrome risk and pharmacodynamic overlap. If switching between SJW and an SSRI, clinicians commonly allow a washout period of ~1–2 weeks (some sources recommend 2 weeks) before starting the other agent — timing depends on the drugs involved and should be directed by a prescriber. Likewise stop SJW before surgery (many perioperative guides advise stopping ~1–2 weeks prior to anesthesia). AAFP
Practical monitoring & advice:
- Start at a standardized dose (e.g. 300 mg × 3/day), document baseline symptoms (PHQ-9 or similar), and reassess at 4–8 weeks.
- If on any prescription meds — consult your clinician or pharmacist first (see interactions below).
- Avoid in pregnancy and breastfeeding unless advised by a specialist (active constituents can pass into milk). Drugs.com
Scientific Evidence for Depression:
Systematic reviews & meta-analyses consistently find that St. John’s wort extracts are superior to placebo and, in many trials, comparable to standard antidepressants (for mild–moderate depression) in short-term trials. However, heterogeneity in extracts, trial quality, and severity of depression studied mean the evidence is strongest for mild–moderate depression and less clear for severe depression. Cochrane
- Cochrane review (systematic review of randomized trials): review of many trials concluded SJW extracts are more effective than placebo and may be comparable to standard antidepressants in mild-to-moderate depression (but trial heterogeneity is a limitation). Cochrane
- Older BMJ meta-analysis and other systematic reviews reached similar conclusions (benefit vs placebo; similar efficacy vs standard antidepressants for mild/moderate). BMJ
- More recent meta-analyses and reviews (2010s–2020s) continue to show benefit for mild-moderate depression but call attention to variability in extract composition, trial quality, and safety (especially interactions). See 2016–2023 reviews/meta-analyses for updates. ScienceDirect
Summary: evidence supports short-term effectiveness of standardized St. John’s wort extracts for mild–moderate depression, and many trials find similar effect sizes to SSRIs for those patients. Evidence is insufficient or not supportive to recommend SJW as a sole therapy for severe depression or where there is high suicide risk — those patients need specialized care. Cochrane
Specific Warnings for Depression:
Major interaction mechanisms
- Potent induction of cytochrome P450 enzymes (especially CYP3A4) and P-glycoprotein → can decrease blood levels (and effectiveness) of many drugs (including oral contraceptives, antiretrovirals, immunosuppressants, warfarin, some chemotherapies, certain anticonvulsants, and many others). This is one of the most clinically relevant harms. U.S. Food and Drug Administration
- Pharmacodynamic risk — serotonin syndrome: combining SJW with SSRIs/SNRIs/MAOIs or other serotonergic agents (e.g., triptans, certain opioids, linezolid, some herbal products) can raise the risk of serotonin syndrome (rare but potentially life-threatening). Do not self-combine SJW with prescription antidepressants. NCCIH
Important documented interactions / clinical consequences
- Oral contraceptives: SJW can reduce contraceptive hormone levels, leading to breakthrough bleeding and risk of unintended pregnancy. Official regulators have issued advice about this interaction. If you use hormonal contraception, discuss alternatives/backup methods with a clinician before using SJW. GOV.UK
- Antiretrovirals / antivirals: SJW reduces levels of some HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors (dangerous; can cause loss of viral control). Contraindicated with many antiretrovirals. Drugs.com
- Immunosuppressants (e.g., cyclosporine, tacrolimus): induction can reduce levels and increase graft-rejection risk — dangerous in transplant patients. Drugs.com
- Warfarin / anticoagulants: interaction potential — may affect INR and clotting risk; monitor closely if coadministration is unavoidable. Drugs.com
- Oral cancer drugs / chemotherapies: interactions reported; avoid without specialist input. Drugs.com
Other adverse effects & cautions
- Photosensitivity: some people (esp. fair-skinned) can get increased sun sensitivity / rash. Avoid tanning beds / excessive sun exposure while taking SJW. Christchurch Medicines Info Service
- Pregnancy & breastfeeding: avoid unless a specialist recommends otherwise — constituents have been detected in milk and safety in pregnancy is not established. Drugs.com
- Surgery / anesthesia: SJW may interact with anesthetics and other perioperative drugs — many perioperative guidelines say stop SJW ~1–2 weeks before surgery. e-SAFE Anaesthesia
Practical safety rules (short)
- Do not self-combine with prescription antidepressants (SSRIs, SNRIs, MAOIs) or other serotonergic meds. If you and your prescriber decide to switch between treatments, use a washout strategy under medical supervision (commonly ~1–2 weeks depending on the drugs). AAFP
- If you take any prescription medicines (especially birth control, HIV meds, transplant meds, anticoagulants, chemotherapy, anticonvulsants), talk to your prescriber/pharmacist first — SJW may be contraindicated. Drugs.com
General Information (All Ailments)
What It Is
St. John’s wort (Hypericum perforatum) is a yellow-flowering herb native to Europe that has been used in traditional medicine for centuries, especially for mood and nervous-system complaints. In modern integrative care it is most commonly taken as capsules, tablets, tinctures, or tea for mild to moderate depressive symptoms, anxiety, sleep disturbance, and somatic stress symptoms.
How It Works
Its activity appears to be multi-mechanistic rather than “one target”:
- Neurotransmitter modulation — Hyperforin and hypericin in the plant appear to inhibit reuptake of serotonin, norepinephrine, and dopamine, modestly increasing synaptic availability (pharmacologically overlapping with SSRIs/SNRIs, but generally weaker per-dose).
- Neuroendocrine effects — Some evidence suggests down-modulation of the HPA stress axis and possible circadian influences.
- Anti-inflammatory and antioxidant actions — In vitro and in-vivo work shows reduced pro-inflammatory cytokines and oxidative stress, both relevant to depression biology in some patients.
- Neuroplastic effects — Emerging evidence suggests increases in brain-derived neurotrophic factor (BDNF) and related pathways that support synaptic remodeling, a mechanism shared by several antidepressants.
Why It’s Important
For selected patients with mild to moderate depressive symptoms, St. John’s wort can achieve clinically meaningful mood improvement comparable to low-dose conventional antidepressants in several randomized trials — often with better subjective tolerability (less sexual dysfunction and weight gain, especially). It provides an accessible, inexpensive, non-scheduled option that gives some people an on-ramp to treatment when they wish to avoid or delay prescription antidepressants, or as a bridge while arranging formal care. Its demonstrated biologic activity also helps dispel the misconception that “herbal” means “biologically trivial.”
Considerations
- High-risk drug–drug interactions — St. John’s wort induces CYP3A4, CYP2C9, P-glycoprotein and other pathways. It can lower blood levels and effectiveness of oral contraceptives, anticoagulants (e.g., warfarin), calcineurin inhibitors (e.g., cyclosporine, tacrolimus), chemotherapy, antiretrovirals, anti-epileptics, some cardiovascular drugs, and many others.
- Serotonin-related risk when combined — Combining with SSRIs, SNRIs, MAOIs, triptans, MDMA, or other serotonergic substances can precipitate serotonin toxicity.
- Inconsistent potency — Over-the-counter preparations differ markedly in hyperforin/hypericin content; clinical-trial-grade extracts are standardized.
- Not first-line for severe depression — Evidence is strongest for mild to moderate symptoms; severe or psychotic depression, bipolar depression, suicidality, and complex comorbidity warrant supervised medical care.
- Photosensitivity and tolerability — Can increase sun sensitivity at higher doses; other adverse effects include GI upset, restlessness, insomnia, and headache.
- Reproductive considerations — Induction of drug metabolism can reduce oral contraceptive effectiveness; unintended pregnancy risk should be explicitly addressed.
Helps with these conditions
St. Johns Wort is most effective for general wellness support with emerging research . The effectiveness varies by condition based on clinical evidence and user experiences.
Detailed Information by Condition
Depression
Active constituents: St. John’s wort extracts contain several biologically active compounds, chiefly hyperforin and hypericin, plus flavonoids and oth...
OCD
St. John’s wort is well-studied for mild–moderate depression, but the evidence for treating OCD is limited and mixed. A few small open-label studies s...
Carpal Tunnel Syndrome
Anti-inflammatory activity (theoretical): Extracts of St John’s wort can down-regulate inflammatory mediators (e.g., COX-2 and iNOS) in cell and anima...
Seasonal Affective Disorder
St. John’s wort (Hypericum perforatum) contains active constituents (notably hyperforin and hypericin) that appear to increase levels of neurotransmit...
Trigeminal Neuralgia
Proposed mechanisms (preclinical): Extracts and constituents (notably hypericin and hyperforin) have antinociceptive actions in animal models of neuro...
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Helps With These Conditions
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