St. John's Wort is a herbal supplement primarily researched for its efficacy in treating depressive disorders. Extensive meta-analyses and systematic reviews indicate it is effective for mild-to-moderate depression, often with results comparable to standard antidepressants.

Evidence by Condition

Major/Mild-to-Moderate Depression Strong

Multiple systematic reviews and meta-analyses demonstrate efficacy comparable to SSRIs and placebo.

Postmenopausal Symptoms Moderate

Evidence suggests effectiveness for managing postmenopausal symptoms and associated depression.

Anxiety and Mood Disorders Moderate

Research supports its use in certain mood and anxiety disorders.

Dental Pain Insufficient

Systematic reviews have investigated its use for dental pain, but evidence remains limited.

Effective Doses

Specific dose ranges are not broadly detailed, though one study utilized a 300mg extract (STEI 300).

Key Findings

St. John's wort is effective for major depression (PMID: 18843608)
Meta-analyses support its use for major depressive disorder (PMID: 27589952)
Hypericum extract has shown efficacy compared to imipramine and placebo (PMID: 10591711)
The supplement may assist with postmenopausal symptoms and depression (PMID: 31331546)

Limitations

Research is heavily focused on depression, with significant gaps regarding its efficacy for dental pain and human cognitive enhancement.

Safety & Interactions

While studies evaluate the safety and tolerability of the supplement, specific drug-drug interactions and contraindications are not detailed in the provided research.

AI-generated summary from 43 peer-reviewed studies. Not medical advice. Always consult a healthcare provider.

Drug-Supplement Interactions

Abemaciclib 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Abemaciclib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Abiraterone 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Abiraterone

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Acalabrutinib 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Acalabrutinib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Alpelisib 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Alpelisib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Antiarrhythmics 🔴 Critical

Mechanism: St Johns Wort is a moderate inducer of CYP2C9, which increases metabolism of CYP2C9 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of amiodarone (antiarrhythmics), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of amiodarone. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Anticoagulants 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Apixaban, Edoxaban, Rivaroxaban, Dicoumarol

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Anticonvulsants 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of carbamazepine (anticonvulsants), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of carbamazepine. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Antidiarrheals 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of P-gp, which increases metabolism of P-gp substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of loperamide (antidiarrheals), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of loperamide. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Antifungals 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of fluconazole (antifungals), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of fluconazole. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Antiplatelet Drugs 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Cilostazol, Ticagrelor, Vorapaxar

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Antipsychotics 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of haloperidol (antipsychotics), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of haloperidol. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Antiretrovirals 🔴 Critical

Mechanism: St. John's wort induces CYP3A4 and P-gp, dramatically reducing protease inhibitor and NNRTI levels.

Effect: Subtherapeutic antiretroviral levels; treatment failure; viral resistance

Management: Absolutely avoid combination. Life-threatening interaction for HIV patients.

Evidence: well-established

Apremilast 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Apremilast

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Artemether 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Artemether

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Avatrombopag 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Avatrombopag

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Axitinib 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Axitinib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Beta-2 Agonists 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of salmeterol (beta2-agonists), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of salmeterol. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Bortezomib 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Bortezomib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Bosutinib 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Bosutinib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Brigatinib 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Brigatinib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

CFTR Modulators 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of ivacaftor (cftr-modulators), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of ivacaftor. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Cabozantinib 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Cabozantinib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Calcium Channel Blockers 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of nifedipine (calcium-channel-blockers), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of nifedipine. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Chemotherapy 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of doxorubicin (chemotherapy), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of doxorubicin. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Cobicistat 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Cobicistat

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Corticosteroids 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Deflazacort

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Cyclosporine 🔴 Critical

Mechanism: St. John's wort induces CYP3A4 and P-glycoprotein, dramatically increasing cyclosporine metabolism.

Effect: Subtherapeutic cyclosporine levels; transplant rejection risk

Management: Absolutely avoid combination. Life-threatening interaction for transplant patients.

Evidence: well-established

Dexfenfluramine 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Dexfenfluramine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Digoxin 🔴 Critical

Mechanism: St. John's wort induces P-glycoprotein, increasing digoxin efflux and reducing plasma levels.

Effect: Subtherapeutic digoxin levels; loss of heart rate control

Management: Avoid combination. If unavoidable, monitor digoxin levels and adjust dose.

Evidence: well-established

Dolasetron 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Dolasetron

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Doxepin (topical) 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Doxepin (topical)

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Eliglustat 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Eliglustat

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Ethinylestradiol 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Ethinylestradiol

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Fenfluramine 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Fenfluramine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Fostamatinib 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Fostamatinib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

GI Prokinetics 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of cisapride (gi-prokinetics), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of cisapride. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Granisetron 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Granisetron

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Hydrocodone 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Hydrocodone

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Immunosuppressants 🔴 Critical

Mechanism: St. John's wort induces CYP3A4 and P-gp, increasing metabolism of tacrolimus and other immunosuppressants.

Effect: Subtherapeutic immunosuppressant levels; transplant rejection risk

Management: Absolutely avoid combination in transplant patients.

Evidence: well-established

Iobenguane (I-131) 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Iobenguane (I-131)

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Ivacaftor 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Ivacaftor

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Leukotriene Antagonists 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of montelukast (leukotriene-antagonists), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of montelukast. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Lorcaserin 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Lorcaserin

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Methadone 🔴 Critical

Mechanism: St. John's wort induces CYP3A4 and P-gp, significantly increasing methadone metabolism.

Effect: Severe methadone withdrawal symptoms; subtherapeutic levels

Management: Avoid combination. Can precipitate acute withdrawal.

Evidence: well-established

Methylene blue 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Methylene blue

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Naldemedine 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Naldemedine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Naloxegol 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Naloxegol

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Nephrotoxic Drugs 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Tacrolimus

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Ondansetron 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Ondansetron

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Opioids 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of methadone (opioids), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of methadone. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Osilodrostat 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Osilodrostat

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

PDE5 Inhibitors 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of sildenafil (pde5-inhibitors), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of sildenafil. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Palonosetron 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Palonosetron

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Praziquantel 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Praziquantel

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Rolapitant 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Rolapitant

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

SNRI 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of venlafaxine (snri), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of venlafaxine. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Sibutramine 🔴 Critical

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Sibutramine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Ssri 🔴 Critical

Mechanism: St. John's wort inhibits serotonin reuptake and induces CYP enzymes that metabolize SSRIs. Combined use risks serotonin syndrome.

Effect: Serotonin syndrome (agitation, confusion, tachycardia, hyperthermia); also reduced SSRI efficacy via enzyme induction

Management: Avoid combination. Serotonin syndrome can be life-threatening. Allow 2-week washout between St. John's wort and SSRIs.

Evidence: well-established

Statins 🔴 Critical

Mechanism: St Johns Wort is a strong inducer of CYP3A4, which increases metabolism of CYP3A4 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of simvastatin (statins), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of simvastatin. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Warfarin 🔴 Critical

Mechanism: St. John's wort induces CYP2C9 and CYP3A4, increasing warfarin metabolism.

Effect: Reduced anticoagulant effect; subtherapeutic INR

Management: Avoid combination. If used, monitor INR frequently and adjust warfarin dose.

Evidence: well-established

ARB 🟡 Moderate

Mechanism: St Johns Wort is a moderate inducer of CYP2C9, which increases metabolism of CYP2C9 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of losartan (arb), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of losartan. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Afatinib 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Afatinib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Alcohol 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Ethanol, Ethanol

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Aldesleukin 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Aldesleukin

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Alimemazine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Alimemazine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Aminolevulinic acid (topical) 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Aminolevulinic acid (topical)

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Aminophylline 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Aminophylline

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Analgesics 🟡 Moderate

Mechanism: St Johns Wort is a weak inducer of CYP1A2, which increases metabolism of CYP1A2 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of acetaminophen (analgesics), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of acetaminophen. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Antibiotics 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Clarithromycin

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Antidiabetic Drugs 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Canagliflozin, Saxagliptin, Linagliptin, Repaglinide

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Antihistamines 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Promethazine, Promethazine, Promethazine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Aprepitant 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Aprepitant

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Azelastine (nasal) 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Azelastine (nasal)

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Benzodiazepines 🟡 Moderate

Mechanism: St. John's wort induces CYP3A4, increasing metabolism of alprazolam, midazolam, and other benzodiazepines.

Effect: Reduced sedative effect; decreased benzodiazepine efficacy

Management: Monitor for reduced efficacy. May need dose adjustment.

Evidence: probable

Beta Blockers 🟡 Moderate

Mechanism: St Johns Wort is a moderate inducer of CYP2C19, which increases metabolism of CYP2C19 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of propranolol (beta-blockers), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of propranolol. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Betrixaban 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Betrixaban

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Binimetinib 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Binimetinib

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Brimonidine (ophthalmic) 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Brimonidine (ophthalmic)

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Brimonidine (topical) 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Brimonidine (topical)

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Brompheniramine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Brompheniramine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Busulfan 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Busulfan

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Cabazitaxel 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Cabazitaxel

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Caffeine 🟡 Moderate

Mechanism: St Johns Wort is a weak inducer of CYP1A2, which increases metabolism of CYP1A2 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of caffeine (caffeine), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of caffeine. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Carbinoxamine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Carbinoxamine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Cetirizine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Cetirizine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Chloroquine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Chloroquine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Chlorphenesin 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Chlorphenesin

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Chlorpheniramine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Chlorpheniramine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Clemastine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Clemastine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Clindamycin 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Clindamycin

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Clofedanol 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Clofedanol

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Codeine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Codeine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Cyproheptadine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Cyproheptadine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Dexbrompheniramine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Dexbrompheniramine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Diphenhydramine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Diphenhydramine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Dopamine Agonists 🟡 Moderate

Mechanism: St Johns Wort is a weak inducer of CYP1A2, which increases metabolism of CYP1A2 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of ropinirole (dopamine-agonists), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of ropinirole. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Doxylamine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Doxylamine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Dronabinol 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Dronabinol

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Elagolix 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Elagolix

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Hydroxychloroquine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Hydroxychloroquine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Iobenguane (I-123) 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Iobenguane (I-123)

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Ioflupane I-123 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Ioflupane I-123

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Levocetirizine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Levocetirizine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

MAOI 🟡 Moderate

Mechanism: St Johns Wort is a weak inducer of CYP1A2, which increases metabolism of CYP1A2 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of rasagiline (maoi), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of rasagiline. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Macimorelin 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Macimorelin

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Mefloquine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Mefloquine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Melatonin 🟡 Moderate

Mechanism: St Johns Wort is a weak inducer of CYP1A2, which increases metabolism of CYP1A2 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of melatonin (melatonin), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of melatonin. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Mepyramine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Mepyramine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Methoxsalen 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Methoxsalen

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Montelukast 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Montelukast

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Morphine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Morphine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Morphine (liposomal) 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Morphine (liposomal)

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

NSAIDs 🟡 Moderate

Mechanism: St Johns Wort is a moderate inducer of CYP2C9, which increases metabolism of CYP2C9 substrates, potentially reducing their plasma concentrations and therapeutic efficacy.

Effect: Reduced plasma levels of ibuprofen (nsaids), potentially leading to therapeutic failure.

Management: Monitor for reduced efficacy of ibuprofen. Dose adjustment may be necessary. Consider alternative supplement or consult healthcare provider.

Evidence: cyp-inferred

Nabilone 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Nabilone

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Nitisinone 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Nitisinone

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Olopatadine (nasal) 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Olopatadine (nasal)

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Opium 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Opium

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Oral Contraceptives 🟡 Moderate

Mechanism: St. John's wort induces CYP3A4, increasing metabolism of estrogen in oral contraceptives.

Effect: Reduced contraceptive efficacy; breakthrough bleeding; unintended pregnancy risk

Management: Avoid combination. Use alternative contraception or avoid St. John's wort.

Evidence: well-established

Oxtriphylline 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Oxtriphylline

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Paclitaxel 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Paclitaxel

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Pentoxyverine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Pentoxyverine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Ppis 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Rabeprazole, Omeprazole, Dexlansoprazole, Esomeprazole, Lansoprazole, Pantoprazole

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Quinine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Quinine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Retinoids 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Tretinoin, Bexarotene

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Roflumilast 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Roflumilast

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Simvastatin 🟡 Moderate

Mechanism: St. John's wort induces CYP3A4, increasing simvastatin metabolism.

Effect: Reduced simvastatin levels; loss of lipid-lowering effect

Management: Monitor lipid levels. May need dose adjustment or switch to pravastatin.

Evidence: well-established

Theophylline 🟡 Moderate

Mechanism: St. John's wort induces CYP1A2, increasing theophylline metabolism.

Effect: Reduced theophylline levels; loss of bronchodilation

Management: Monitor theophylline levels. May need dose increase.

Evidence: probable

Treprostinil 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Treprostinil

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Tricyclic Antidepressants 🟡 Moderate

Mechanism: St. John's wort induces CYP2C19 and CYP3A4, increasing metabolism of tricyclic antidepressants.

Effect: Reduced antidepressant levels; loss of efficacy

Management: Monitor antidepressant levels. Avoid combination if possible.

Evidence: probable

Trimethobenzamide 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Trimethobenzamide

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Tripelennamine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Tripelennamine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Triprolidine 🟡 Moderate

Mechanism: Interaction identified from DDInter 2.0 database. Specific drugs: Triprolidine

Effect: See mechanism description

Management: Consult healthcare provider before combining.

Evidence: ddinter-verified

Verapamil 🟡 Moderate

Mechanism: St. John's wort induces CYP3A4, increasing verapamil metabolism.

Effect: Reduced verapamil levels; loss of blood pressure/heart rate control

Management: Monitor blood pressure and heart rate. May need dose adjustment.

Evidence: probable

⚠️ This information is for educational purposes only and does not constitute medical advice. Always consult your healthcare provider before combining supplements with medications.

Claims vs. Evidence

100% Evidence-Backed

0% Unsupported

78% Structure/Function

Claim Type	% of Products	Evidence Required	Status
All Other	99%	Tier D (Unclassified)	✅ Supported
Structure/Function	78%	Tier C (DSHEA Structure/Function (no pre-approval))	✅ Supported
Nutrient	2%	Tier D (Unknown)	✅ Supported
No Claim	1%	Tier D (No claim on label)	✅ Supported

Research by Topic

St. John'S Wort 23 studies

SYS St John's wort for major depression

MET A systematic review of St. John's wort for major depressive ...

SYS St John's wort for depression

+20 more

St Johns Wort 11 studies

RCT The effect of Hypericum perforatum on postmenopausal symptom...

RCT Hypericum extract LI 160 and fluoxetine in mild to moderate ...

REG Interaction: St Johns Wort × Cyclosporine

+8 more

St Johns Wort Depression 4 studies

MET Clinical use of Hypericum perforatum (St John's wort) in dep...

RCT Hypericum extract versus imipramine or placebo in patients w...

MET A systematic review and meta-analysis of Hypericum perforatu...

+1 more

Magnesium 1 studies

MET Efficacy of Pharmacological Interventions in Milder Depressi...

Ginkgo 1 studies

MET The risk-benefit profile of commonly used herbal therapies: ...

Rhodiola 1 studies

SYS Herbal medicines, other than St. John's Wort, in the treatme...

Garlic 1 studies

SYS Natural health product-drug interactions: a systematic revie...

Dietary Supplement General 1 studies

CLI Neuroimaging of St. John's Wort-Induced Changes of Serotonin...

⚠️ FDA Safety Data

Adverse Event Profile: St Johns Wort

Research Evidence (43)

Meta Analysis: 16 Systematic Review: 14 Rct: 7 Regulatory Source: 4 Clinical Trial: 1 Openfda Safety: 1

B St John's wort for major depression

Systematic Review The Cochrane database of systematic reviews 2008 n=5489

**Linde et al., 2008** | Cochrane Database Syst Rev | Systematic Review Linde Klaus, Berner Michael M, Kriston Levente. St John's wort for major depression. Cochrane Database Syst Rev. 2008-Oct-08;2008(4):CD000448. doi:10.1002/14651858.CD000448.pub3 ...

PubMed DOI

B Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis

Meta Analysis Journal of affective disorders 2017 n=3808

INTRODUCTION: St John's wort is a popular herbal remedy recommended by Traditional Chinese Medicine (TCM) practitioners and licensed and widely prescribed for depression in many European countries. However, conflicting data regarding its benefits and...

PubMed DOI

B A systematic review of St. John's wort for major depressive disorder

Meta Analysis Systematic reviews 2016 n=2922

**Apaydin et al., 2016** | Syst Rev | Meta Analysis Apaydin Eric A, Maher Alicia R, ... Hempel Susanne. A systematic review of St. John's wort for major depressive disorder. Syst Rev. 2016-Sep-02;5(1):148. doi:10.1186/s13643-016-0325-2 BACKGROUND: Th...

PubMed DOI

B St John's wort for depression

Systematic Review The Cochrane database of systematic reviews 2000 n=2291

**Linde et al., 2000** | Cochrane Database Syst Rev | Systematic Review Linde K, Mulrow C D. St John's wort for depression. Cochrane Database Syst Rev. 2000(2):CD000448 BACKGROUND: Extracts of the plant Hypericum perforatum L. (popularly called St. J...

PubMed

B Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis

Meta Analysis Neuropsychopharmacology reports 2025 n=1049

**Urata et al., 2025** | Neuropsychopharmacol Rep | Meta Analysis Urata Minoru, Sakurai Hitoshi, ... Watanabe Koichiro. Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis. Neuropsychopharmacol Rep. 2...

PubMed DOI

B St John's wort for depression

Meta Analysis The Cochrane database of systematic reviews 2005 n=37

**Linde et al., 2005** | Cochrane Database Syst Rev | Meta Analysis Linde K, Mulrow C D, ... Egger M. St John's wort for depression. Cochrane Database Syst Rev. 2005-Apr-18(2):CD000448 BACKGROUND: Extracts of the plant Hypericum perforatum L. (popula...

PubMed

C St John's wort for depression: meta-analysis of randomised controlled trials

Meta Analysis The British journal of psychiatry : the journal of mental science 2005

**Linde et al., 2005** | Br J Psychiatry | Meta Analysis Linde Klaus, Berner Michael, ... Mulrow Cynthia. St John's wort for depression: meta-analysis of randomised controlled trials. Br J Psychiatry. 2005-Feb;186:99-107 BACKGROUND: Extracts of Hyper...

PubMed

C The effect of Hypericum perforatum on postmenopausal symptoms and depression: A randomized controlled trial

Rct Complementary therapies in medicine 2019 n=40

**Eatemadnia et al., 2019** | Complement Ther Med | Rct Eatemadnia Alieh, Ansari Somayeh, ... Najar Shahnaz. The effect of Hypericum perforatum on postmenopausal symptoms and depression: A randomized controlled trial. Complement Ther Med. 2019-Aug;45...

PubMed DOI

C Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks

Rct BMJ (Clinical research ed.) 1999 n=263

OBJECTIVES: To assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression. DESIGN: Randomised, double bli...

PubMed

C Hypericum perforatum as a cognitive enhancer in rodents: A meta-analysis

Meta Analysis Scientific reports 2016

**Ben-Eliezer et al., 2016** | Sci Rep | Meta Analysis Ben-Eliezer Daniel, Yechiam Eldad. Hypericum perforatum as a cognitive enhancer in rodents: A meta-analysis. Sci Rep. 2016-Oct-20;6:35700. doi:10.1038/srep35700 Considered an antidepressant and a...

PubMed DOI

C Kava and St. John's Wort: current evidence for use in mood and anxiety disorders

Systematic Review Journal of alternative and complementary medicine (New York, N.Y.) 2009

**Sarris et al., 2009** | J Altern Complement Med | Systematic Review Sarris Jerome, Kavanagh David J. Kava and St. John's Wort: current evidence for use in mood and anxiety disorders. J Altern Complement Med. 2009-Aug;15(8):827-36. doi:10.1089/acm.2...

PubMed DOI

C Large-scale observational studies of hypericum extracts in patients with depressive disorders--a systematic review

Systematic Review Phytomedicine : international journal of phytotherapy and phytopharmacology 2005 n=100

**Linde et al., 2005** | Phytomedicine | Systematic Review Linde K, Knüppel L. Large-scale observational studies of hypericum extracts in patients with depressive disorders--a systematic review. Phytomedicine. 2005-Jan;12(1-2):148-57 We present a sys...

PubMed

C Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis

Meta Analysis Progress in neuro-psychopharmacology & biological psychiatry 2009 n=4

**Rahimi et al., 2009** | Prog Neuropsychopharmacol Biol Psychiatry | Meta Analysis Rahimi Roja, Nikfar Shekoufeh, Abdollahi Mohammad. Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective seroton...

PubMed DOI

C Hypericum perforatum L. preparations for menopause: a meta-analysis of efficacy and safety

Meta Analysis Climacteric : the journal of the International Menopause Society 2014

**Liu et al., 2014** | Climacteric | Meta Analysis Liu Y-R, Jiang Y-L, ... Dong J-X. Hypericum perforatum L. preparations for menopause: a meta-analysis of efficacy and safety. Climacteric. 2014-Aug;17(4):325-35. doi:10.3109/13697137.2013.861814 OBJE...

PubMed DOI

C A systematic review and meta-analysis on the use of Hypericum perforatum (St. John's Wort) for pain conditions in dental practice

Systematic Review Homeopathy : the journal of the Faculty of Homeopathy 2012

**Raak et al., 2012** | Homeopathy | Systematic Review Raak Christa, Büssing Arndt, ... Ostermann Thomas. A systematic review and meta-analysis on the use of Hypericum perforatum (St. John's Wort) for pain conditions in dental practice. Homeopathy. 2...

PubMed DOI

C Co-administration of St. John's wort and hormonal contraceptives: a systematic review

Systematic Review Contraception 2016

**Berry-Bibee et al., 2016** | Contraception | Systematic Review Berry-Bibee Erin N, Kim Myong-Jin, ... Curtis Kathryn M. Co-administration of St. John's wort and hormonal contraceptives: a systematic review. Contraception. 2016-Dec;94(6):668-677. do...

PubMed DOI

C The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava

Meta Analysis Annals of internal medicine 2002

**Ernst et al., 2002** | Ann Intern Med | Meta Analysis Ernst Edzard. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava. Ann Intern Med. 2002-Jan-01;136(1):42-53 Because us...

PubMed

C Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review

Systematic Review Alternative medicine review : a journal of clinical therapeutic 2011

**Dwyer et al., 2011** | Altern Med Rev | Systematic Review Dwyer Anna V, Whitten Dawn L, Hawrelak Jason A. Herbal medicines, other than St. John's Wort, in the treatment of depression: a systematic review. Altern Med Rev. 2011-Mar;16(1):40-9 OBJECTI...

PubMed

C The safety of St John's wort (Hypericum perforatum) in pregnancy and lactation: A systematic review of rodent studies

Systematic Review Phytotherapy research : PTR 2018

**Avila et al., 2018** | Phytother Res | Systematic Review Avila Catharine, Whitten Dawn, Evans Sue. The safety of St John's wort (Hypericum perforatum) in pregnancy and lactation: A systematic review of rodent studies. Phytother Res. 2018-Aug;32(8):...

PubMed DOI

C Hypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study in outpatients

Rct European archives of psychiatry and clinical neuroscience 2005

**Bjerkenstedt et al., 2005** | Eur Arch Psychiatry Clin Neurosci | Rct Bjerkenstedt Lars, Edman Gunnar V, ... Mannel Marcus. Hypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study ...

PubMed

C Efficacy of Cimicifuga racemosa, Hypericum perforatum and Agnus castus in the treatment of climacteric complaints: a systematic review

Systematic Review Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 2012

**Laakmann et al., 2012** | Gynecol Endocrinol | Systematic Review Laakmann Elena, Grajecki Donata, ... Buhling Kai J. Efficacy of Cimicifuga racemosa, Hypericum perforatum and Agnus castus in the treatment of climacteric complaints: a systematic rev...

PubMed DOI

C Interaction: St Johns Wort × Cyclosporine

Regulatory Source

**Severity**: CRITICAL **Evidence**: well-established St. John's wort induces CYP3A4 and P-glycoprotein, dramatically increasing cyclosporine metabolism. Subtherapeutic cyclosporine levels; transplant rejection risk Absolutely avoid combination. Life...

C Interaction: St Johns Wort × Oral Contraceptives

Regulatory Source

**Severity**: MODERATE **Evidence**: well-established St. John's wort induces CYP3A4, increasing metabolism of estrogen in oral contraceptives. Reduced contraceptive efficacy; breakthrough bleeding; unintended pregnancy risk Avoid combination. Use al...

C Interaction: St Johns Wort × Ssri

Regulatory Source

**Severity**: CRITICAL **Evidence**: well-established St. John's wort inhibits serotonin reuptake and induces CYP enzymes that metabolize SSRIs. Combined use risks serotonin syndrome. Serotonin syndrome (agitation, confusion, tachycardia, hyperthermi...

C Interaction: St Johns Wort × Warfarin

Regulatory Source

**Severity**: CRITICAL **Evidence**: well-established St. John's wort induces CYP2C9 and CYP3A4, increasing warfarin metabolism. Reduced anticoagulant effect; subtherapeutic INR Avoid combination. If used, monitor INR frequently and adjust warfarin d...

C A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review

Meta Analysis International clinical psychopharmacology 2001

The herbal remedy St John's wort is widely used as an antidepressant but its efficacy has not been systematically investigated. Meta-analyses and systematic reviews of published trials strongly suggest St John's wort is more effective than placebo al...

PubMed

C Adverse effects of St. John's Wort: a systematic review

Systematic Review The Journal of clinical psychiatry 2004 n=100

**Knüppel et al., 2004** | J Clin Psychiatry | Systematic Review Knüppel Lars, Linde Klaus. Adverse effects of St. John's Wort: a systematic review. J Clin Psychiatry. 2004-Nov;65(11):1470-9 OBJECTIVE: To obtain an overview of the available clinical ...

PubMed

C Hyperforin plasma level as a marker of treatment adherence in the National Institutes of Health Hypericum Depression Trial

Rct Journal of clinical psychopharmacology 2005 n=340

BACKGROUND: A previously reported clinical trial of Hypericum perforatum (St John's wort) in depression did not demonstrate efficacy. We assessed treatment adherence by measuring plasma hyperforin and evaluated the possible impact of adherence on stu...

PubMed

C St John's Wort (Hypericum perforatum)--a herbal antidepressant

Meta Analysis Current medical research and opinion 1998

**Hippius et al., 1998** | Curr Med Res Opin | Meta Analysis Hippius H. St John's Wort (Hypericum perforatum)--a herbal antidepressant. Curr Med Res Opin. 1998;14(3):171-84 A number of clinical studies conducted over the past few years have indicated...

PubMed

C St. John's wort for depression: a meta-analysis of well-defined clinical trials

Meta Analysis The Journal of nervous and mental disease 1999

**Kim et al., 1999** | J Nerv Ment Dis | Meta Analysis Kim H L, Streltzer J, Goebert D. St. John's wort for depression: a meta-analysis of well-defined clinical trials. J Nerv Ment Dis. 1999-Sep;187(9):532-8 Studies concluding that St. John's wort (H...

PubMed

C [Hypericum perforatum extract in treatment of mild to moderate depression. Clinical and pharmacological aspects]

Meta Analysis Der Nervenarzt 2002

**Laakmann et al., 2002** | Nervenarzt | Meta Analysis Laakmann G, Jahn G, Schüle C. [Hypericum perforatum extract in treatment of mild to moderate depression. Clinical and pharmacological aspects]. Nervenarzt. 2002-Jul;73(7):600-12 For many years, h...

PubMed

C Cluster analysis of symptoms during antidepressant treatment with Hypericum extract in mildly to moderately depressed out-patients. A meta-analysis of data from three randomized, placebo-controlled trials

Meta Analysis Psychopharmacology 2002

**Kasper et al., 2002** | Psychopharmacology (Berl) | Meta Analysis Kasper S, Dienel A. Cluster analysis of symptoms during antidepressant treatment with Hypericum extract in mildly to moderately depressed out-patients. A meta-analysis of data from t...

PubMed

C An update on clinical drug interactions with the herbal antidepressant St. John's wort

Systematic Review Current drug metabolism 2008

**Zhou et al., 2008** | Curr Drug Metab | Systematic Review Zhou Shu-Feng, Lai Xinsheng. An update on clinical drug interactions with the herbal antidepressant St. John's wort. Curr Drug Metab. 2008-Jun;9(5):394-409 St. John's wort (Hypericum perfora...

PubMed

C How effective is St John's wort? The evidence revisited

Meta Analysis The Journal of clinical psychiatry 2004 n=15

**Werneke et al., 2004** | J Clin Psychiatry | Meta Analysis Werneke Ursula, Horn Oded, Taylor David M. How effective is St John's wort? The evidence revisited. J Clin Psychiatry. 2004-May;65(5):611-7 BACKGROUND: St. John's wort (Hypericum perforatum...

PubMed

C Clinical investigation of the antidepressant effectiveness of hypericum

Meta Analysis Journal of geriatric psychiatry and neurology 1994 n=10

**Harrer et al., 1994** | J Geriatr Psychiatry Neurol | Meta Analysis Harrer G, Schulz V. Clinical investigation of the antidepressant effectiveness of hypericum. J Geriatr Psychiatry Neurol. 1994-Oct;7 Suppl 1:S6-8 To date, 25 controlled therapy stu...

PubMed

C St John's wort (Hypericum perforatum): drug interactions and clinical outcomes

Systematic Review British journal of clinical pharmacology 2002

**Henderson et al., 2002** | Br J Clin Pharmacol | Systematic Review Henderson L, Yue Q Y, ... Arlett P. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol. 2002-Oct;54(4):349-56 AIMS: The aim of this ...

PubMed

C Natural health product-drug interactions: a systematic review of clinical trials

Systematic Review Therapeutic drug monitoring 2005 n=14

**Mills et al., 2005** | Ther Drug Monit | Systematic Review Mills Edward, Wu Ping, ... Guyatt Gordon. Natural health product-drug interactions: a systematic review of clinical trials. Ther Drug Monit. 2005-Oct;27(5):549-57 Interactions between natur...

PubMed

C Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.)

Systematic Review European journal of clinical pharmacology 1998

**Ernst et al., 1998** | Eur J Clin Pharmacol | Systematic Review Ernst E, Rand J I, ... Stevinson C. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol. 1998-Oct;54(8):589-94 UNLABELL...

PubMed

D Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression

Rct Advances in therapy 2002 n=70

**Behnke et al., 2002** | Adv Ther | Rct Behnke Kirsten, Jensen Gert Saaby, ... Gruenwald Joerg. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression. Adv Ther. 2002;19(1):43-52 In a randomized, controlled, double-bl...

PubMed

D Efficacy of continuation treatment with hypericum perforatum in depression

Rct The Journal of clinical psychiatry 2002

**Brenner et al., 2002** | J Clin Psychiatry | Rct Brenner Ronald, Madhusoodanan S, Pawlowska Monika. Efficacy of continuation treatment with hypericum perforatum in depression. J Clin Psychiatry. 2002-May;63(5):455 *No abstract available* *Requires ...

PubMed

D Predicting stable treatment response in patients with major depression treated with hypericum extract WS 5570/5572

Rct Pharmacopsychiatry 2005

**Kieser et al., 2005** | Pharmacopsychiatry | Rct Kieser M, Szegedi A. Predicting stable treatment response in patients with major depression treated with hypericum extract WS 5570/5572. Pharmacopsychiatry. 2005-Sep;38(5):194-200 OBJECTIVE: Recent r...

PubMed

D Neuroimaging of St. John's Wort-Induced Changes of Serotonin Metabolism in Normal Subjects

Clinical Trial ClinicalTrials.gov 1999

**NCT ID**: NCT00001919 **Phase**: **Status**: COMPLETED **Enrollment**: 13 **Completion**: 2002-06

ClinicalTrials.gov

D Adverse Event Profile: St Johns Wort

Openfda Safety FDA CAERS

**Source**: FDA Center for Food Safety and Applied Nutrition (CFSAN) Adverse Event Reporting System **Total Events**: 3 **Serious Events**: 1 **Date Range**: 20140624 to 20200727 - **Suicidal ideation**: 1

Related Supplements

Kava 2 shared sources Saw Palmetto 1 shared sources Rhodiola 1 shared sources Magnesium 1 shared sources Ginseng 1 shared sources Ginkgo 1 shared sources Garlic 1 shared sources Echinacea 1 shared sources

Frequently Asked Questions

What is St. John's Wort and what is it used for?

St. John's Wort is an herbal supplement primarily used to treat depressive disorders. It is most commonly researched for its effectiveness in managing mild-to-moderate depression.

Does St. John's Wort work for depression?

Yes, there is strong evidence that St. John's Wort is effective for treating mild-to-moderate depression. Many studies show that its results are often comparable to standard antidepressants like SSRIs.

Can St. John's Wort help with anxiety or postmenopausal symptoms?

There is moderate evidence supporting the use of St. John's Wort for certain anxiety and mood disorders. Additionally, research suggests it may be effective for managing postmenopausal symptoms and related depression.

Is St. John's Wort effective for dental pain?

There is currently insufficient evidence to confirm if St. John's Wort works for dental pain. While systematic reviews have looked into this, the research remains limited.

What is the recommended dose of St. John's Wort?

Specific effective dose ranges are not broadly detailed in current research. However, one study specifically utilized a 300mg extract (STEI 300).

Are there any dangerous drug interactions with St. John's Wort?

Yes, St. John's Wort has critical interactions with several important medications, including cyclosporine, SSRIs, and warfarin. It also has a moderate interaction with oral contraceptives, which may reduce their effectiveness.

Who should avoid taking St. John's Wort?

Individuals taking blood thinners (warfarin), immunosuppressants (cyclosporine), or antidepressants (SSRIs) should avoid this supplement due to severe interaction risks. You should also consult a doctor if you use oral contraceptives.

Answers generated from research evidence. Not medical advice.