St. John's Wort Drug Interactions, Uses, Effectiveness, Safety & More
What is this page for?
First and foremost: how St. John's Wort interacts with medications. The heart of this page is the interaction list — every drug St. John's Wort is known to interact with, and how serious each one is.
But these pages have grown well beyond that into a full monograph — what St. John's Wort is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy
Check St. John's Wort against your medication
Add one medicationSt. John's Wort Drug Interactions: The Bottom Line
From the HelloPharmacist Editorial Team · Updated July 2026Based on the available evidence, the overall risk of a clinically significant St. John's Wort drug interaction is high, and this supplement affects more medications, and more seriously, than most people expect. Most of its documented interactions are rated major, none are minor, and many are confirmed in well-controlled human studies.
The biggest concerns are medicines where a drop in drug levels can cause real harm. St. John's Wort can weaken warfarin and other blood thinners, reduce the effect of birth control pills enough to allow unplanned pregnancy, and lower levels of transplant medications such as cyclosporine and tacrolimus, which has led to organ rejection. It can also reduce the effectiveness of HIV medicines, certain cancer treatments like irinotecan and imatinib, seizure medicines such as phenytoin and phenobarbital, and digoxin.
The list of interacting medications is long because St. John's Wort speeds up enzymes and transport proteins the body uses to clear many drugs, so it can lower the levels of a wide range of medicines at once. Unlike many supplements, these effects are not just theoretical; a large share have been shown directly in people. The strength of the effect can also depend on the specific extract used.
Based on HelloPharmacist’s St. John's Wort interaction data and reviewed under our editorial standards.
Drugs that interact with St. John's Wort
1143 medications have a known interaction with St. John's Wort, graded by severity. Select any drug for the full evidence-based detail.
756 major interactions. These combinations can be clinically significant — best avoided, or used only with close professional supervision. Always check with your pharmacist before combining them with St. John's Wort.
Don’t want to scroll the list? Just ask.
Tell us the medications you take and we’ll check each one against St. John's Wort using our pharmacist-reviewed interaction data.
AI summaries are generated from our St. John's Wort interaction data for education only — always confirm with your pharmacist. How we use AI
No drugs match “”.
What Severity, Likelihood & Evidence Mean
Severity — How Serious It Can Be
- Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
- Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
- Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
- No known interaction. Checked against our sources with nothing documented — not the same as proven safety.
Likelihood — How Well It’s Documented
- Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
- Probable. Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
- Possible. Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
- Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Where This Data Comes From
- Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
- Each drug listed above links to the full report for that exact St. John's Wort combination — clinical detail, likelihood, evidence level, and citations.
- Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.
The kinds of drugs St. John's Wort affects
Every type of medication (drug category) St. John's Wort is known to interact with. Open any category for the detail — or search your exact drug in the checker above.
Alprazolam (Xanax)
St. John's wort increases the clearance of alprazolam and decreases its effects.
Alprazolam, which is used as a probe for cytochrome P450 3A4 (CYP3A4) activity, has a two-fold increase in clearance when given with St. John's wort. St. John's wort reduces the half-life of alprazolam from 12.4 hours to 6 hours.
Contraceptive Drugs
St. John's wort increases the clearance of contraceptive drugs and reduces their clinical effects.
Females taking St. John's wort and oral contraceptives concurrently should use an additional or alternative form of birth control. St. John's wort can decrease norethindrone and ethinyl estradiol levels by 13% to 15%, resulting in breakthrough bleeding, irregular menstrual bleeding, or unplanned pregnancy. Bleeding irregularities usually occur within a week of starting St. John's wort and regular cycles usually return when St. John's wort is discontinued. Unplanned pregnancy has occurred with concurrent use of oral contraceptives and St. John's wort extract. St. John's wort is thought to induce the cytochrome P450 1A2 (CYP1A2), 2C9 (CYP2C9), and 3A4 (CYP3A4) enzymes, which are responsible for metabolism of progestins and estrogens in contraceptives.
Cyclosporine (Neoral, Sandimmune)
St. John's wort reduces the levels and clinical effects of cyclosporine.
Concomitant use can decrease plasma cyclosporine levels by 30% to 70%. Using St. John's wort with cyclosporine in patients with heart, kidney, or liver transplants can cause subtherapeutic cyclosporine levels and acute transplant rejection. This interaction has occurred with a St. John's wort extract standardized to 0.3% hypericin and dosed at 300-600 mg per day. Withdrawal of St. John's wort can result in a 64% increase in cyclosporine levels. St. John's wort induces cytochrome P450 3A4 (CYP3A4) and the multi-drug transporter, P-glycoprotein/MDR-1, which increases cyclosporine clearance.
Cytochrome P450 3A4 (Cyp3A4) Substrates
St. John's wort increases the metabolism and reduces the levels of CYP3A4 substrates.
St. John's wort induces CYP3A4 enzymes and increases metabolism of CYP3A4 substrates. Clinically significant interactions have been reported with St. John's wort products containing hyperforin 1 mg or more.
Digoxin (Lanoxin)
St. John's wort reduces the levels and clinical effects of digoxin.
St. John's wort can reduce the bioavailability, serum levels, and therapeutic effects of digoxin. Taking an extract of St. John's wort 900 mg, containing hyperforin 7.5 mg or more, daily for 10-14 days, can reduce serum digoxin levels by 25% in healthy people. St. John's wort is thought to affect the multidrug transporter, P-glycoprotein, which mediates the absorption and elimination of digoxin and other drugs. St. John's wort products providing less than 7.5 mg of hyperforin daily do not appear to affect digoxin levels.
Docetaxel (Taxotere)
St. John's wort reduces the levels and clinical effects of docetaxel.
Clinical research shows that taking a specific St. John's wort product (Hyperiplant, VSM) 300 mg three times daily for 14 days increases docetaxel clearance by about 14%, resulting in decreased plasma concentrations of docetaxel in cancer patients. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort.
Imatinib (Gleevec)
St. John's wort reduces the levels and clinical effects of imatinib.
Taking St. John's wort 900 mg daily for 2 weeks reduces the bioavailability and half-life of a single dose of imatinib and decreases its serum levels by 30% in healthy volunteers. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, which increases clearance of imatinib.
Irinotecan (Camptosar)
St. John's wort reduces the levels and clinical effects of irinotecan.
St. John's wort 900 mg daily for 18 days decreases serum levels of irinotecan by at least 50%. Clearance of the active metabolite of irinotecan, SN-38, is also increased, resulting in a 42% decrease in the area under the concentration-time curve. This is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort.
Mephenytoin (Mesantoin)
St. John's wort reduces the levels and clinical effects of mephenytoin.
Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces cytochrome P450 2C19 (CYP2C19) and significantly increases metabolism of mephenytoin (Mesantoin). In people with wild-type 2C19, metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism.
Non-Nucleoside Reverse Transcriptase Inhibitors (Nnrtis)
St. John's wort decreases the levels and clinical effects of NNRTIs.
St. John's wort increases the oral clearance of nevirapine (Viramune) by 35%. Subtherapeutic concentrations are associated with therapeutic failure, development of viral resistance, and development of drug class resistance. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter.
Omeprazole (Prilosec)
St. John's wort decreases the levels and clinical effects of omeprazole.
Taking St. John's wort, 300 mg orally three times daily for 14 days, reduces serum concentrations of omeprazole by inducing its metabolism via cytochrome P450 (CYP) 2C19 and 3A4. The reduction of omeprazole serum levels is dependent on CYP2C19 genotype, with reductions up to 50% in extensive metabolizers and 38% in poor metabolizers.
Oxycodone (Oxycontin)
St. John's wort decreases the levels and clinical effects of oxycodone.
St. John's wort can increase oxycodone metabolism by inducing cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity.
P-Glycoprotein Substrates
St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.
St. John's wort induces P-glycoprotein. P-glycoprotein is a carrier mechanism responsible for transporting drugs and other substances across cell membranes. When P-glycoprotein is induced in the gastrointestinal (GI) tract, it can prevent the absorption of some medications. In addition, induction of p-glycoprotein can decrease entry of drugs into the central nervous system (CNS) and decrease access to other sites of action.
Phenobarbital (Luminal)
St. John's wort decreases the levels and clinical effects of phenobarbital.
St. John's wort may increase the metabolism of phenobarbital. Plasma concentrations of phenobarbital should be monitored carefully. The dose of phenobarbital may need to be increased when St. John's wort is started and decreased when it is stopped.
Phenprocoumon (Marcoumar, Others)
St. John's wort decreases the levels and clinical effects of phenprocoumon.
St. John's wort appears to increase the metabolism of phenprocoumon (an anticoagulant that is not available in the US) by increasing the activity of the cytochrome P450 2C9 (CYP2C9) enzyme. This may result in decreases in the anticoagulant effect and international normalized ratio (INR).
Phenytoin (Dilantin)
St. John's wort decreases the levels and clinical effects of phenytoin.
St. John's wort may increase the metabolism of phenytoin. Plasma concentrations of phenytoin should be monitored closely. The dose of phenytoin may need to be increased when St. John's wort is started and decreased when it is stopped.
Protease Inhibitors (Pis)
St. John's wort reduces the levels and clinical effects of PIs.
In healthy volunteers, St. John's wort can reduce the plasma concentrations of indinavir (Crixivan) by inducing cytochrome P450 3A4 (CYP3A4). This might result in treatment failure and viral resistance. St. John's wort also induces P-glycoprotein, which can result in decreased intracellular protease inhibitor concentrations and increased elimination.
Rivaroxaban (Xarelto)
St. John's wort decreases the levels and clinical effects of rivaroxaban.
A small pharmacokinetic study in healthy volunteers shows that taking a single dose of rivaroxaban 20 mg after using a specific St. John's wort extract (Jarsin, Vifor SA) 450 mg orally twice daily for 14 days reduces the bioavailability of rivaroxaban by 24% and reduces rivaroxaban's therapeutic inhibition of factor Xa by 20%.
Tacrolimus (Prograf)
St. John's wort decreases the levels and clinical effects of tacrolimus.
Taking a St. John's wort extract (Jarsin) 600 mg daily significantly decreases tacrolimus serum levels. Dose increases of 60% may be required to maintain therapeutic tacrolimus levels in patients taking St. John's wort. St. John's wort is thought to lower tacrolimus levels by inducing cytochrome P450 3A4 (CYP3A4) enzymes. A small clinical study in healthy adults also shows that taking St. John's wort 300 mg three times daily for 10 days decreases the total systemic exposure to tacrolimus by 27% and 33% after taking a single 5 mg dose of immediate-release or prolonged-release tacrolimus, respectively.
Warfarin (Coumadin)
St. John's wort decreases the levels and clinical effects of warfarin.
Taking St. John's wort significantly increases clearance of warfarin, including both its R- and S-isomers. This is likely due to induction of cytochrome P450 (CYP) 1A2 and CYP3A4. St. John's wort can also significantly decrease International Normalized Ratio (INR) in people taking warfarin. In addition, taking warfarin at the same time as St. John's wort might reduce warfarin bioavailability. When a dried extract is mixed with warfarin in an aqueous medium, up to 30% of warfarin is bound to particles, reducing its absorption.
Aminolevulinic Acid
St. John's wort might have additive phototoxic effects with aminolevulinic acid.
Concomitant use with St. John's wort extract may cause synergistic phototoxicity. Delta-aminolevulinic acid can cause a burning erythematous rash and severe swelling of the face, neck, and hands when taken with St. John's wort.
Bupropion (Wellbutrin)
St. John's wort might reduce the levels and effects of bupropion.
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%. This effect is attributed to the induction of cytochrome P450 2B6 (CYP2B6) by St. John's wort.
Clopidogrel (Plavix)
St. John's wort might increase the levels and effects of clopidogrel.
Taking St. John's wort with clopidogrel seems to increase the activity of clopidogrel. In clopidogrel non-responders, taking St. John's wort seems to induce metabolism of clopidogrel to its active metabolite by cytochrome P450 enzymes 3A4 and 2C19. This leads to increased antiplatelet activity. Theoretically, this might lead to an increased risk of bleeding in clopidogrel responders.
Clozapine (Clozaril)
St. John's wort might decrease the levels and clinical effects of clozapine.
A case report describes a female with schizophrenia controlled on clozapine who had a return of symptoms when she started taking St. John's wort. The plasma concentration of clozapine was reduced, likely because its clearance was increased due to induction of the cytochrome P450 enzymes 3A4, 1A2, 2C9, and 2C19 by St. John's wort.
Cytochrome P450 1A2 (Cyp1A2) Substrates
St. John's wort may increase the metabolism and reduce the levels of CYP1A2 substrates.
Clinical and in vitro research shows that St. John's wort induces CYP1A2, but to a lesser extent than CYP3A4.
Cytochrome P450 2B6 (Cyp2B6) Substrates
St. John's wort may increase the metabolism and reduce the levels of CYP2B6 substrates.
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion, a CYP2B6 substrate, reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%.
Cytochrome P450 2C19 (Cyp2C19) Substrates
St. John's wort may increase the metabolism and reduce the levels of CYP2C19 substrates.
Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces CYP2C19 and increases metabolism of mephenytoin (Mesantoin). In patients with wild-type 2C19 (2C19*1/*1) metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism. Theoretically, St. John's wort might increase metabolism of other CYP2C19 substrates.
Cytochrome P450 2C9 (Cyp2C9) Substrates
St. John's wort may increase the metabolism and reduce the levels of CYP2C9 substrates.
There is contradictory research about the effect of St. John's wort on CYP2C9. Some in vitro research shows that St. John's wort induces CYP2C9, but to a lesser extent than CYP3A4. St. John's wort also induces metabolism of the S-warfarin isomer, which is a CYP2C9 substrate. Other research shows that St. John's wort 300 mg three times daily for 21 days does not significantly affect the pharmacokinetics of a single 400 mg dose of ibuprofen, which is also a CYP2C9 substrate. Until more is known, use St. John's wort cautiously in patients who are taking CYP2C9 substrates.
Fentanyl
Theoretically, St. John's wort may reduce the levels and clinical effects of fentanyl.
Given that St. John's wort induces cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, it is possible that concomitant use of St. John's wort with fentanyl will reduce plasma levels and analgesic activity of fentanyl. However, some clinical research in healthy adults shows that taking St. John's wort (LI-160, Lichtwer Pharma) 300 mg daily for 21 days does not alter the pharmacokinetics or clinical effects of intravenous fentanyl. It is unclear if these findings can be generalized to oral, intranasal, or transdermal fentanyl.
Fexofenadine (Allegra)
St. John's wort may increase the levels and clinical effects of fexofenadine.
A single dose of St. John's wort decreases the clearance of fexofenadine and increases its plasma levels. However, the effect of St. John's wort on plasma levels of fexofenadine seems to be lost if dosing is continued for more than 2 weeks. Patients taking fexofenadine and St. John's wort concurrently should be monitored for possible fexofenadine toxicity.
Finasteride (Proscar, Propecia)
St. John's wort may reduce the levels and clinical effects of finasteride.
St. John's wort reduces plasma levels of finasteride in healthy male volunteers due to induction of finasteride metabolism via cytochrome P450 3A4 (CYP3A4). The clinical significance of this interaction is not known.
Gliclazide (Diamicron, Others)
St. John's wort may reduce the levels and clinical effects of gliclazide.
Taking St. John's wort decreases the half-life and increases clearance of gliclazide in healthy people.
Hmg-Coa Reductase Inhibitors ("Statins")
St. John's wort may increase the metabolism and reduce the effectiveness of atorvastatin, lovastatin, and rosuvastatin. However, it does not seem to affect pravastatin, pitavastatin, or fluvastatin.
Concomitant use of St. John's wort can reduce plasma concentrations of the active simvastatin metabolite, simvastatin hydroxy acid, by 28%. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter. This increases simvastatin clearance. It also increases the clearance of atorvastatin (Lipitor), lovastatin (Mevacor), and rosuvastatin (Crestor). St. John's wort does not seem to affect the plasma concentrations of pravastatin (Pravachol), pitavastatin (Livalo) or fluvastatin (Lescol), which are not substrates of CYP3A4 or P-glycoprotein.
Indinavir (Crixivan)
St. John's wort may reduce the levels and clinical effects of indinavir.
In healthy volunteers, taking St. John's wort concurrently with indinavir reduces plasma concentrations of indinavir by inducing metabolism via cytochrome P450 3A4 (CYP3A4). Theoretically, this could result in treatment failure and viral resistance.
Ivabradine (Corlanor)
St. John's wort might reduce the levels and clinical effects of ivabradine.
Taking St. John's wort 900 mg containing 7.5 mg of hyperforin daily for 14 days with a single dose of ivabradine causes a 62% reduction in plasma levels of ivabradine. This interaction is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, increasing the metabolism of ivabradine.
Methadone (Dolophine)
St. John's wort might reduce the levels and clinical effects of methadone.
St. John's wort might decrease the effectiveness of methadone by reducing its blood concentrations. In one report, two out of four patients on methadone maintenance therapy for addiction experienced methadone withdrawal symptoms after taking St. John's wort 900 mg daily for a median of 31 days. There was a median decrease in blood methadone concentration of 47% (range: 19% to 60%) when compared to baseline.
Photosensitizing Drugs
Theoretically, St. John's wort might increase the likelihood for photosensitivity reactions when used in combination with photosensitizing drugs.
St. John's wort might increase photosensitivity reactions due to its hypericin content. However, some clinical research shows that very high doses of St. John's wort are needed to produce phototoxicity in humans.
Procainamide
Theoretically, St. John's wort might decrease the levels and clinical effects of procainamide.
Animal research shows that taking St. John's wort extract increases the bioavailability of procainamide, but does not increase its metabolism. Whether this interaction is clinically significant in humans is not known.
Reserpine (Raudixin, Others)
Theoretically, St. John's wort might decrease the effectiveness of reserpine.
Animal research shows that St. John's wort can antagonize the effects of reserpine.
Serotonergic Drugs
Theoretically, St. John's wort might inhibit reuptake and increase levels of serotonin, resulting in additive effects with serotonergic drugs.
Concomitant use of serotonergic drugs with St. John's wort can lead to increased adverse effects and increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstriction disorders.
Tramadol (Ultram)
St. John's wort might decrease the levels and clinical effects of tramadol.
St. John's wort can increase tramadol metabolism via induction of cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity. Theoretically, concurrent use of St. John's wort with tramadol might also cause additive serotonergic effects.
Voriconazole (Vfend)
St. John's wort might decrease the levels and clinical effects of voriconazole.
Clinical research shows that taking St. John's wort with voriconazole reduces voriconazole exposure and increases voriconazole metabolism by approximately 107%. Voriconazole is primarily metabolized by cytochrome P450 (CYP) 2C19, with CYP3A4 and CYP2C9 also involved. St. John's wort induces CYP2C19, CYP3A4, and CYP2C9.
Zolpidem (Ambien)
St. John's wort might decrease the levels and clinical effects of zolpidem.
In clinical research, concomitant use of zolpidem with St. John's wort decreased zolpidem plasma levels due to induction of its metabolism by cytochrome P450 3A4. Whether this interaction is clinically significant is not known.
Ambrisentan (Letairis)
St. John's wort may increase the clearance of ambristentan and decrease its effects.
Clinical research in healthy volunteers shows that taking St. John's wort 900 mg daily decreases the area under the concentration-time curve of ambrisentan 5 mg by 17% to 26%. Ambrisentan clearance was increased by 20% to 35% depending on CYP2C19 genotype. However, these small changes are unlikely to be clinically significant.
Boceprevir (Victrelis)
St. John's wort might decrease the levels and clinical effects of boceprevir.
Boceprevir increases the maximum concentration and concentration at 8 hours of the St. John's wort constituent, hypericin, by approximately 30%. However, St. John's wort does not significantly change the area under the concentration-time curve or maximum plasma concentration of boceprevir 800 mg three times daily in healthy adults.
Methylphenidate (Concerta, Others)
St. John's wort might reduce the levels and clinical effects of methylphenidate.
St. John's wort might decrease the effectiveness of methylphenidate. In one report, an adult male, stabilized on methylphenidate for attention deficit-hyperactivity disorder (ADHD), experienced increased attention problems and ADHD symptoms after taking St. John's wort 600 mg daily for 4 months. ADHD symptoms improved when St. John's wort was discontinued. The mechanism of this interaction is unknown.
Theophylline
St. John's wort might decrease the levels of theophylline, although this effect might not be clinically relevant.
St. John's wort does not seem to significantly affect theophylline pharmacokinetics. There is a single case report of a possible interaction with theophylline. A patient who smoked and was taking 11 other drugs experienced an increase in theophylline levels after discontinuation of St. John's wort. This increase has been attributed to a rebounding of theophylline serum levels after St. John's wort was no longer present to induce metabolism via cytochrome P450 1A2 (CYP1A2). However, studies in healthy volunteers show that St. John's wort is unlikely to affect theophylline to any clinically significant degree.
St. John's Wort: Uses, Safety & Side Effects
St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with prescription medicines and is not safe for everyone, so always talk to your pharmacist or doctor before taking it.
- Scientific name
- Hypericum perforatum
- Family
- Hypericaceae
- Part used
- Flowering tops and aerial parts (leaves and flowers)
- Common forms
- Capsules, tablets, standardized extracts, teas, tinctures, and topical oils
- Mild to moderate depression
- Anxiety and stress
- Sleep problems
- Menopausal symptoms
- Wound healing (topical)
Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.
Generally well tolerated short-term but has many serious drug interactions and can cause sun sensitivity.
When used orally. Preliminary population research has found that taking St. John's wort while pregnant is associated with offspring that develop neura...
Read the full pregnancy detailWhen used orally. Nursing infants of mothers who take St. John's wort have a greater chance of experiencing colic, drowsiness, and lethargy; avoid usi...
Read the full breastfeeding detailPregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.
Overview
St. John's wort is a flowering plant native to Europe that now grows in many parts of the world, including North America and Asia. It has bright yellow flowers and gets its name because it often blooms around the feast day of St. John the Baptist in late June.
People have used this herb for hundreds of years for many health problems. Today it is most commonly taken for low mood and mild depression. It is sold as capsules, tablets, teas, tinctures, and oils, and is one of the most widely used and researched herbal products in the world.
How it works
St. John's wort contains several active compounds, the best known being hypericin and hyperforin. Researchers believe hyperforin may be most responsible for the effects on mood.
Laboratory and animal studies suggest the herb may raise the levels of certain brain chemicals such as serotonin, dopamine, and norepinephrine, which is similar to how some prescription antidepressants work. Much of this understanding comes from lab research, and scientists do not fully understand exactly how it works in people.
Does St. John's Wort work?
How to read these evidence grades
Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.
Likely Effective Depression
Specific formulations of oral St. John's wort are effective for mild or moderate major depressive disorder. St. John's wort may also cause fewer side effects than certain conventional antidepressants.
Possibly Effective Menopausal symptoms
Oral St. John's wort seems to be beneficial for patients with menopausal symptoms.
Possibly Effective Somatic symptom disorder
Oral St. John's wort seems to be beneficial for patients with somatoform disorder.
Possibly Ineffective Burning mouth syndrome
Oral St. John's wort does not appear to reduce pain from burning mouth syndrome.
Possibly Ineffective Hepatitis C
St. John's wort contains hypericin. Synthetic hypericin has been studied and shown to be ineffective as an oral drug for hepatitis C.
Possibly Ineffective HIV/AIDS
St. John's wort contains hypericin. Synthetic hypericin has been studied and shown to be ineffective as an oral and intravenous drug for HIV.
Possibly Ineffective Irritable bowel syndrome (IBS)
Oral St. John's wort does not seem to improve symptoms in patients with IBS.
Possibly Ineffective Peripheral neuropathy
Oral St. John's wort does not seem to relieve pain in patients with peripheral neuropathy.
Possibly Ineffective Social anxiety disorder
Oral St. John's wort does not seem to be beneficial for patients with social anxiety disorder.
Also studied for 23 conditions — evidence insufficient to rate
Insufficient Reliable Evidence To Rate Acne
It is unclear if topical St. John's wort is beneficial for acne.
Insufficient Reliable Evidence To Rate Anxiety
Although there is interest in using oral St. John's wort for anxiety, there is insufficient reliable information about the clinical effects of St. John's wort for this condition.
Insufficient Reliable Evidence To Rate Attention deficit-hyperactivity disorder (ADHD)
It is unclear if oral St. John's wort is beneficial for improving symptoms in children with ADHD.
Insufficient Reliable Evidence To Rate Brain tumor
St. John's wort contains hypericin. Synthetic hypericin has been studied as an oral drug for malignant brain tumors, with unclear benefit.
Insufficient Reliable Evidence To Rate Chronic fatigue syndrome (CFS)
Although there is interest in using oral St. John's wort for CFS, there is insufficient reliable information about the clinical effects of St. John's wort for this condition.
Insufficient Reliable Evidence To Rate Crigler-Najjar syndrome type 2
It is unclear if oral St. John's wort is beneficial for patients with this condition.
Insufficient Reliable Evidence To Rate Fibromyalgia
Although there is interest in using oral St. John's wort for fibromyalgia, there is insufficient reliable information about the clinical effects of St. John's wort for this condition.
Insufficient Reliable Evidence To Rate Genital herpes
Topical St. John's wort has only been evaluated in combination with copper sulfate; its effect when used alone is unclear.
Insufficient Reliable Evidence To Rate Herpes labialis (cold sores)
Topical St. John's wort has only been evaluated in combination with copper sulfate; its effect when used alone is unclear.
Insufficient Reliable Evidence To Rate Mastitis
It is unclear if topical St. John's wort is beneficial for granulomatous mastitis.
Insufficient Reliable Evidence To Rate Memory
It is unclear if oral St. John's wort is beneficial for improving memory in healthy people.
Insufficient Reliable Evidence To Rate Migraine headache
It is unclear if oral St. John's wort is beneficial for reducing migraine headache.
Insufficient Reliable Evidence To Rate Obsessive-compulsive disorder (OCD)
It is unclear if oral St. John's wort is beneficial for reducing OCD symptoms.
Insufficient Reliable Evidence To Rate Osteoarthritis
It is unclear if topical St. John's wort is beneficial for osteoarthritis. Oral St. John's wort is not studied for this use.
Insufficient Reliable Evidence To Rate Polycystic ovary syndrome (PCOS)
Oral St. John's wort has only been evaluated in combination with other ingredients; its effect when used alone is unclear.
Insufficient Reliable Evidence To Rate Premenstrual syndrome (PMS)
It is unclear if oral St. John's wort is beneficial for patients with PMS.
Insufficient Reliable Evidence To Rate Psoriasis
It is unclear if topical St. John's wort improves symptoms in patients with plaque psoriasis.
Insufficient Reliable Evidence To Rate Scleroderma
Topical St. John's wort has only been evaluated in combination with neem oil; its effect when used alone is unclear.
Insufficient Reliable Evidence To Rate Seasonal affective disorder (SAD)
It is unclear if oral St. John's wort is beneficial for patients with SAD.
Insufficient Reliable Evidence To Rate Tinnitus
St. John's wort has only been evaluated in combination with other ingredients; its effect when used alone is unclear.
Insufficient Reliable Evidence To Rate Tobacco and Nicotine Dependence
It is unclear if oral St. John's wort is beneficial for improving rates of smoking cessation.
Insufficient Reliable Evidence To Rate Vaginal candidiasis
It is unclear if topical St. John's wort is beneficial for vulvovaginal candidiasis.
Insufficient Reliable Evidence To Rate Wound healing
Topical St. John's wort seems to improve wound healing and wound-related pain for certain types of surgery, although evidence is limited.
Source & disclaimer. Effectiveness ratings and evidence summaries are provided by Natural Medicines (Therapeutic Research Center) and shown as licensed. Where Natural Medicines hasn’t rated a use, HelloPharmacist’s pharmacists may add their own reviewed rating and evidence (each such entry is labeled). This is educational information, not medical advice — talk with your pharmacist or doctor before starting, stopping, or changing a supplement.
Safety & precautions
For most healthy adults, short-term use is usually well tolerated. However, St. John's wort is known for having many serious interactions with prescription medicines, so it is very important to check with a pharmacist or doctor before starting it.
It can make your skin more sensitive to sunlight, especially in fair-skinned people. People with bipolar disorder should be cautious, as it may trigger mood swings or mania. People scheduled for surgery are often told to stop it beforehand.
Pregnancy and breastfeeding: There is not enough reliable safety information, so it is best to avoid St. John's wort if you are pregnant or breastfeeding. The herb can pass into breast milk and has been linked to side effects in some infants.
Side effects
Common side effects are usually mild and may include stomach upset, dizziness, dry mouth, tiredness, restlessness, headache, and trouble sleeping. Some people notice increased sensitivity to sunlight, which can lead to a rash or sunburn more easily.
A rare but serious risk is serotonin syndrome, a condition caused by too much serotonin in the body. Warning signs include agitation, fast heartbeat, high blood pressure, shivering, sweating, and confusion. This risk is higher when the herb is combined with certain medicines. Seek medical help right away if these symptoms occur.
St. John's Wort: Reported Adverse Effects
Documented safety reports on St. John's Wort from the evidence-graded Natural Medicines (TRC Healthcare) database, shown word-for-word from the licensed record.
Orally, St. John's wort is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, dizziness, dry mouth, gastrointestinal discomfort (mild), fatigue, headache, insomnia, restlessness, and sedation.
Topically: Skin rash and photodermatitis.
Serious Adverse Effects (Rare):
Orally: There have been rare case reports of suicidal ideation and psychosis after taking St. John's wort.
Alopecia Dermatologic
Both topical and chronic oral use of St. John's wort can cause photodermatitis. The average threshold dose range for an increased risk of photosensitivity appears to be 1.8-4 grams St. John's wort extract or 5-10 mg hypericin, daily. Lower doses might not cause this effect. For example, a single dose of St. John's wort extract 1800 mg (5.4 mg hypericin) followed by 900 mg (2.7 mg hypericin) daily does not seem to produce skin hypericin concentrations thought to be high enough to cause phototoxicity. Females appear to have a higher risk of dose-related photosensitivity. In a dose-ranging, small clinical trial, almost all of the female participants experienced mild to moderate photosensitivity with paresthesia in sun-exposed skin areas after administration of St. John's wort (Jarsin, Casella Med) 1800 mg daily for 3-6 days. Symptoms resolved about 12-16 days after discontinuation. Male participants reported no adverse effects at this dose, and both genders reported no adverse effects at lower doses. Light or fair-skinned people should employ protective measures against direct sunlight when using St. John's wort either topically or orally.
Total body erythroderma without exposure to sunlight, accompanied by burning sensation of the skin, has also been reported. Orally, St. John's wort may cause pruritus or skin rash, although these events seem to occur infrequently. A case of persistent scalp and eyebrow hair loss has been reported for a 24-year-old schizophrenic female who was taking olanzapine plus St. John's wort 900 mg/day orally. Also, a case of surgical site irritation has been reported for a patient who applied ointment containing St. John's wort.
- Gulick RM, McAuliffe V, Holden-Wiltse J, et al. Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med 1999;130:510-4.
- Golsch S, Vocks E, Rakoski J, et al. [Reversible increase in photosensitivity to UV-B caused by St. John's wort extract]. Hautarzt 1997;48:249-52.
- Upton R, ed. St. John's wort, Hypericum perforatum: Quality control, analytical and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1997;1-32.
- Schempp CM, Ludtke R, Winghofer B, Simon JC. Effect of topical application of hypericum perforatum extract on skin sensitivity to solar simulated radiation. Photodermatol Photoimmunol Photomed 2000;16:125-8.
- Jacobson JM, Feinman L, Liebes L, et al. Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's Wort plant, in patients with chronic hepatitis C virus infection. Antimicrob Agents Chemother 2001;45:517-24.
- Lane-Brown MM. Photosensitivity associated with herbal preparations of St. John's wort (Hypericum perforatum). Med J Aust 2000;172:302.
- Linde K, Knuppel L. Large-scale observational studies of hypericum extracts in patients with depressive disorders - a systematic review. Phytomedicine 2005;12:148-57.
- Weber W, Vander Stoep A, McCarty RL, et al. Hypericum perforatum (St John's wort) for attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled trial. JAMA 2008;299:2633-41.
- Schempp, C. M., Winghofer, B., Muller, K., Schulte-Monting, J., Mannel, M., Schopf, E., and Simon, J. C. Effect of oral administration of Hypericum perforatum extract (St. John's Wort) on skin erythema and pigmentation induced by UVB, UVA, visible light
- Brattstrom, A. Long-term effects of St. John's wort (Hypericum perforatum) treatment: a 1-year safety study in mild to moderate depression. Phytomedicine. 2009;16(4):277-283.
- Hohmann N, Maus A, CarlsA, Haefeli WE, Mikus G. St. John's wort treatment in women bears risks beyond pharmacokinetic drug interactions. Arch Toxico. 2016;90(4):1013-15. doi:10.1007/s00204-015-1532-7.
- Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T
- Schempp CM, Muller K, Winghofer B, et al. Single-dose and steady-state administration of Hypericum perfotatum extract (St. John's wort) does not influence skin sensitivity to UV radiation, visible light, and solar-stimulated radiation. Arch Dermatol 2001;
- Schulz V. Incidence and clinical relevance of the interactions and side effects of Hypericum preparations. Phytomedicine 2001;8:152-60.
- Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
- Bernd A, Ramirez-Bosca A, Kippenberger S, and et al. Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen. Photochem Photobiol 1999;2(69):218-221.
- Brockmoller J, Reum T, Bauer S, et al. Hypericin and pseudohypericin: pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997;30:94-101.
- Holme SA, Roberts DL. Erythroderma associated with St John's wort. Br J Dermatol 2000;143:1127-8.
- Kasper, S., Volz, H. P., Moller, H. J., Dienel, A., and Kieser, M. Continuation and long-term maintenance treatment with Hypericum extract WS 5570 after recovery from an acute episode of moderate depression--a double-blind, randomized, placebo controlled
- Sultana D, Peindl KS Wisner KL. Rash associated with St. John's wort treatment in premenstrual dysphoric disorder. Arch Women Ment Health 2000;3:99-101.
- Parker V, Wong AH, Boon HS, Seeman MV. Adverse reactions to St John's Wort. Can J Psychiatry 2001;46:77-9.
- Samadi S, Khadivzadeh T, Emami A, et al. The effect of Hypericum perforatum on the wound healing and scar of cesarean. J Altern Complement Med 2010;16:113-7.
Anorexia Psychiatric
St. John's wort can induce hypomania in depressed patients and mania in depressed patients with occult bipolar disorder. Cases of first-episode psychosis have been reported for females who used St. John's wort orally. In both cases, symptoms resolved following discontinuation of St. John's wort and treatment with antipsychotics for several weeks. Also, psychosis and delirium have been reported for a 76-year-old female patient who used St. John's wort for 3 weeks. The patient may have been predisposed to this effect due to undiagnosed dementia. Restlessness, insomnia, panic, and anxiety have been noted for some patients taking St. John's wort orally.
In isolated cases, St. John's wort has been associated with a syndrome consisting of extreme anxiety, confusion, nausea, hypertension, and tachycardia. These symptoms may occur within 2-3 weeks after it is started, in patients with no other predisposing factors. This syndrome has been diagnosed as the serotonin syndrome. In one case, the symptoms began after consuming tyramine-containing foods, including aged cheese and red wine. In an isolated case, a 51-year-old female reported having had suicidal and homicidal thoughts for 9 months while taking vitamin C and a St. John's wort extract. Symptoms disappeared within 3 weeks of discontinuing treatment. A case of decreased libido has been reported for a 42-year-old male with mood and anxiety disorders who had taken St. John's wort orally for 9 months.
St. John's wort has been associated with withdrawal effects similar to those found with conventional antidepressants. Headache, nausea, anorexia, dry mouth, thirst, cold chills, weight loss, dizziness, insomnia, paresthesia, confusion, and fatigue have been reported. Withdrawal effects are most likely to occur within two days after discontinuation but can occur one week or more after stopping treatment in some people. Occurrence of withdrawal symptoms may not be related to dose or duration of use.
- O'Breasail AM, Argouarch S. Hypomania and St John's wort. Can J Psychiatry 1998;43:746-7.
- Schneck C. St. John's wort and hypomania. J Clin Psychiatry 1998;59:689.
- Nierenberg AA, Burt T, Matthews J, et al. Mania associated with St. John's wort. Biol Psychiatry 1999;46:1707-8.
- Moses EL, Mallinger AG. St. John's wort: Three cases of possible mania induction. J Clin Psychopharmacol 2000;20:115-7.
- Hammerness P, Basch E, Ulbricht C, et al. St. John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics 2003;44:271-82.
- Barbenel, D. M., Yusufi, B., O'Shea, D., and Bench, C. J. Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline. J Psychopharmacol 2000;14(1):84-86.
- Guzelcan, Y., Scholte, W. F., Assies, J., and Becker, H. E. [Mania during the use of a combination preparation with St. John's wort (Hypericum perforatum)]. Ned.Tijdschr.Geneeskd. 10-6-2001;145(40):1943-1945.
- Andreescu, C., Mulsant, B. H., and Emanuel, J. E. Complementary and alternative medicine in the treatment of bipolar disorder--a review of the evidence. J.Affect.Disord. 2008;110(1-2):16-26.
- Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T
- Shimizu K, Nakamura M, Isse K, Nathan PJ. First-episode psychosis after taking an extract of Hypericum perforatum (St John's Wort). Hum Psychopharmacol 2004;19:275-6.
- Gurok MG, Mermi O, Kilic F, et al. Psychotic episode induced by St. John's wort (Hypericum perforatum): a case report. J Mood Dis 2014;4(1):38-40.
- Laird RD and Webb M. Psychotic episode during use of St John's wort. J Herbal Pharmacother 2001;1(2):81-87.
- Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998;54:589-94.
- Linde K, Knuppel L. Large-scale observational studies of hypericum extracts in patients with depressive disorders - a systematic review. Phytomedicine 2005;12:148-57.
- van Gurp, G., Meterissian, G. B., Haiek, L. N., McCusker, J., and Bellavance, F. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 2002;48:905-912.
- Papakostas, G. I., Crawford, C. M., Scalia, M. J., and Fava, M. Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. A replication of findings with the use of a double-blind, placebo-controlled trial of Hyp
- Woelk H, Burkard G, and Grunwald J. Nutzen und Risikobewertung des Hypericum-extraktes LI 160 auf der Basis einer Drug-Monitoring-Studie mit 3250 patienten. Nervenheilkunde 1993;12:308-313.
- Schakau D, Hiller K, Schultz-Zehden W, and et al. Risk/benefit profile of St.John's wort extract: STEI 300 in 2404 patients with various degrees of psychiatric disturbance. Psychopharmakotherapie 1996;3:116-122.
- Yildirim O, Canan F. A case of panic attack induced by St John's wort. Prim Care Companion CNS Disord 2013;15(1). pii: PCC.12l01453.
- Brown TM. Acute St. John's wort toxicity. Am J Emerg Med 2000;18:231-2.
- Parker V, Wong AH, Boon HS, Seeman MV. Adverse reactions to St John's Wort. Can J Psychiatry 2001;46:77-9.
- Patel S, Robinson R, Burk M. Hypertensive crisis associated with St. John's Wort. Am J Med 2002;112:507-8.
- Nanayakkara, P. W., Meijboom, M., and Schouten, J. A. [Suicidal and aggressive thoughts as a result of taking a Hypericum preparation (St. John's wort)]. Ned.Tijdschr.Geneeskd. 6-11-2005;149(24):1347-1349.
- Bhopal JS. St John's wort-induced sexual dysfunction. Can J Psychiatry 2001;46:456-457.
- Beckman SE, Sommi RW, Switzer J. Consumer use of St. John's wort: A survey of effectiveness, safety, and tolerability. Pharmacotherapy 2000;20:568-74.
- Dean AJ, Moses GM, Vernon JM. Suspected withdrawal syndrome after cessation of St. John's wort. Ann Pharmacother 2003;37:150.
Anorexia Gastrointestinal
Orally, St. John's wort may cause dyspepsia, anorexia, diarrhea, nausea, vomiting, and constipation, although these events seems to occur infrequently.
- Schrader E. Equivalence of St. John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol 2000;15:61-8.
- Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ 2005;330:503.
- Weber W, Vander Stoep A, McCarty RL, et al. Hypericum perforatum (St John's wort) for attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled trial. JAMA 2008;299:2633-41.
- van Gurp, G., Meterissian, G. B., Haiek, L. N., McCusker, J., and Bellavance, F. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 2002;48:905-912.
- Lecrubier, Y., Clerc, G., Didi, R., and Kieser, M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry 2002;159(8):1361-1366.
- Fava, M., Alpert, J., Nierenberg, A. A., Mischoulon, D., Otto, M. W., Zajecka, J., Murck, H., and Rosenbaum, J. F. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J.Clin.Psychopharmacol. 2005;25(5
- Al-Akoum, M., Maunsell, E., Verreault, R., Provencher, L., Otis, H., and Dodin, S. Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause. 2009;16(2):307-314.
- Canning, S., Waterman, M., Orsi, N., Ayres, J., Simpson, N., and Dye, L. The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. CNS.Drugs 2010;24(3):207-225.
- Schrader E, Meier B, and Brattstrom A. Hypericum treatment of mild-moderate depression in a placebo-controlled study. A prospective, double-blind, randomized, placebo-controlled, multicentre study. Human Psychopharm 1998;13:163-169.
Antidepressant-induced sexual dysfunction Genitourinary
Orally, St. John's wort can cause intermenstrual or abnormal menstrual bleeding. However, this effect has occurred in patients who were also taking an oral contraceptive. Changes in menstrual bleeding might be the result of a drug interaction. Also, St. John's wort has been associated with anorgasmia and frequent urination when used orally.
Sexual dysfunction can occur with St. John's wort, but less frequently than with SSRIs. A case of erectile dysfunction and orgasmic delay has been reported for a 49-year-old male after taking St. John's wort orally for one week. Co-administration of sildenafil 25-50 mg prior to sexual activity reversed the sexual dysfunction. Previously, the patient had experienced orgasmic delay, erectile dysfunction, and inhibited sexual desire when taking a selective serotonin reuptake inhibitor (sertraline).
- Yue QY, Bergquist C, Gerden B. Safety of St. John's wort (Hypericum perforatum). Lancet 2000;355:576-7.
- Ratz, A. E., von Moos, M., and Drewe, J. [St. John's wort: a pharmaceutical with potentially dangerous interactions]. Schweiz Rundsch.Med Prax. 5-10-2001;90(19):843-849.
- Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized controlled trial. JAMA 2002;287:1807-14.
- van Gurp, G., Meterissian, G. B., Haiek, L. N., McCusker, J., and Bellavance, F. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 2002;48:905-912.
- Assalian P. Sildenafil for SJW-induced sexual dysfunction. J Sex Marital Ther 2000;26:357-8.
Cataracts Ocular/Otic
There is concern that taking St. John's wort might increase the risk of cataracts. The hypericin constituent of St. John's wort is photoactive and, in the presence of light, may damage lens proteins, leading to cataracts. In population research, people with cataracts were significantly more likely to have used St. John's wort compared to people without cataracts. Ear and labyrinth disorders have been possibly attributed to use of St. John's wort in clinical research, although these events rarely occur.
- Roberts JE, Wang RH, Tan IP, et al. Hypericin (active ingredient in St. John's wort) photo-oxidation of lens proteins. Photochem Photobiol 1999;69:42S.
- Booth JN, McGwin G. The association between self-reported cataracts and St. John's Wort. Curr Eye Res 2009;34:863-6.
- Gastpar, M., Singer, A., and Zeller, K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacops
Cholestasis Hepatic
A case of acute hepatitis with prolonged cholestasis and features of vanishing bile duct syndrome has been reported for a patient who used tibolone and St. John's wort orally for 10 weeks. A case of jaundice with transaminitis and hyperbilirubinemia has been reported for a 79 year-old female who used St. John's wort and copaiba. Laboratory values normalized 7 weeks after discontinuation of both products.
- Etogo-Asse, F., Boemer, F., Sempoux, C., and Geubel, A. Acute hepatitis with prolonged cholestasis and disappearance of interlobular bile ducts following tibolone and Hypericum perforatum (St. John's wort). Case of drug interaction? Acta Gastroenterol.Be
- Agollo MC, Miszputen SJ, Diament J. Hypericum perforatum-induced hepatotoxicity with possible association with copaiba (copaifera langsdorffii desf): a case report. Einstein (Sao Paulo) 2014;12(3):355-7.
Cluster headache Neurologic/CNS
St. John's wort may cause headache, dizziness, fatigue, lethargy, or insomnia. Isolated cases of paresthesia have been reported for patients taking St. John's wort. A case of subacute toxic neuropathy has been reported for a 35-year-old female who took St. John's wort 500 mg daily orally for 4 weeks.
- Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St. John's wort in major depression: A randomized, placebo-controlled trial. JAMA 2001;285:1978-86.
- Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ 2005;330:503.
- van Gurp, G., Meterissian, G. B., Haiek, L. N., McCusker, J., and Bellavance, F. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 2002;48:905-912.
- Lecrubier, Y., Clerc, G., Didi, R., and Kieser, M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry 2002;159(8):1361-1366.
- Fava, M., Alpert, J., Nierenberg, A. A., Mischoulon, D., Otto, M. W., Zajecka, J., Murck, H., and Rosenbaum, J. F. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J.Clin.Psychopharmacol. 2005;25(5
- Papakostas, G. I., Crawford, C. M., Scalia, M. J., and Fava, M. Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. A replication of findings with the use of a double-blind, placebo-controlled trial of Hyp
- Sardella, A., Lodi, G., Demarosi, F., Tarozzi, M., Canegallo, L., and Carrassi, A. Hypericum perforatum extract in burning mouth syndrome: a randomized placebo-controlled study. J.Oral Pathol.Med. 2008;37(7):395-401.
- Canning, S., Waterman, M., Orsi, N., Ayres, J., Simpson, N., and Dye, L. The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. CNS.Drugs 2010;24(3):207-225.
- Abdali K, Khajehei M, Tabatabaee HR. Effect of St John's wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2010;17(2):326-31.
- Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998;54:589-94.
- Bove GM. Acute neuropathy after exposure to sun in a patient treated with St. John's Wort. Lancet 1998;352:1121-2.
Depression Endocrine
A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a 67-year-old male with depression has been reported. During a 3-month period, the patient was taking St. John's wort 300 mg daily then increased to 600-900 mg daily with no adverse effects despite a low serum sodium level of 122mEq/L, elevated levels of urine sodium, and urine osmolality suggestive of SIADH. St. John's wort appeared to be the only contributing factor. The patient's sodium level normalized 3 weeks after discontinuation of St. John's wort.
Hypertension Cardiovascular
In clinical research, palpitations have been reported for patients taking St. John's wort orally, although the number of these events was higher for the patients taking sertraline. In one case report, an adult female developed recurrent palpitations and supraventricular tachycardia (SVT) within 3 weeks of initiating St. John's wort 300 mg daily. SVT and related symptoms responded to Valsalva maneuvers and did not recur after discontinuing therapy.
Edema has also been reported in clinical research for some patients treated with St. John's wort 900-1500 mg daily for 8 weeks. Cardiovascular collapse following induction of anesthesia has been reported in an otherwise healthy patient who had been taking St. John's wort for 6 months. A case of St. John's wort-induced hypertension has been reported for a 56-year-old patient who used St. John's wort extract 250 mg twice daily for 5 weeks. Blood pressure normalized after discontinuation of treatment. A case of new-onset orthostatic hypotension and light-headedness has been reported for a 70 year-old homebound patient who was taking multiple prescription medications and herbal products, including St. John's wort. When all herbal products were discontinued, these symptoms improved, and the patient experienced improvement in pain control.
- van Gurp, G., Meterissian, G. B., Haiek, L. N., McCusker, J., and Bellavance, F. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 2002;48:905-912.
- Fisher KA, Patel P, Abualula S, Concepion L. St. John's Wort-Induced Supraventricular Tachycardia. Cureus. 2021 Apr 7;13(4):e14356.
- Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized controlled trial. JAMA 2002;287:1807-14.
- Irefin S, Sprung J. A possible cause of cardiovascular collapse during anesthesia: long-term use of St. John's Wort. J Clin Anesth 2000;12:498-9.
- Zullino, D. and Borgeat, F. Hypertension induced by St. John's Wort - a case report. Pharmacopsychiatry 2003;36(1):32.
- Cappuzzo, K. A. Herbal product use in a patient with polypharmacy. Consult Pharm. 2006;21(11):911-915.
Kidney failure Renal
Orally, St. John's wort has been associated with a case report of acute kidney failure in a 46-year-old female after one dose of homemade St. John's wort tea. Three sessions of hemodialysis were required before there was full recovery. However, causality is unclear since the patient had also been taking diclofenac intermittently for a month prior to developing kidney failure.
Pain Musculoskeletal
Orally, St. John's wort may cause muscle or joint stiffness, tremor, muscle spasms, or pain, although these events appear to occur rarely.
Pharyngitis Pulmonary/Respiratory
Orally, St. John's wort may cause sore throat, swollen glands, laryngitis, sinus ache, sweating, and hot flashes, although the frequency of these events appears to be similar to placebo.
Sjogren syndrome Other
Sjogren's syndrome has been reported in a patient taking herbal supplements including St. John's wort, echinacea, and kava. Echinacea may have been the primary cause, because Sjogren's syndrome is an autoimmune disorder. The role of St. John's wort in causing this syndrome is unclear.
Adverse-effects data: Natural Medicines, Therapeutic Research Center
Dosing
There is no single official dose for St. John's wort. Products vary widely in strength, and many studies use extracts standardized to a set amount of hypericin or hyperforin. Because of this, the right dose depends on the specific product.
The safest approach is to follow the directions on the product label and to choose a standardized extract from a reputable brand. Always talk with your pharmacist or doctor before starting, so they can check for interactions and help you use it safely. Effects on mood, if any, may take several weeks to appear.
St. John's Wort & Pregnancy
St. John's Wort & Breastfeeding
© 2026 Therapeutic Research Center
Pregnancy & lactation ratings: Natural Medicines, Therapeutic Research Center
References & further reading
The 152 references that drive our St. John's Wort monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.
- Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.
Parts of this content are provided by the Therapeutic Research Center, LLC.
DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
© 2021 Therapeutic Research Center, LLC
Brands that make products with St. John's Wort
303 brands in our database make a supplement containing St. John's Wort.
Supplement products with St. John's Wort
1,160 products in our database contain St. John's Wort. Open any to see its full ingredient list and every drug interaction we check.
St. John's Wort: Common Questions
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Products that contain St. John's Wort
A rotating sample of real supplements in our database that list St. John's Wort — open any to see its full ingredients and every drug interaction we check.
- Mood Complex by Nutricost
- St. John's Wort 900 mcg by Healths Harmony
- Depression Tamer by Remedys Nutrition
- St. John's Wort Extract (600 mg) by BulkSupplements.com
- St. John's Wort 300 mg by Nature's Way
- Anxiety Relief by Herbal Terra
- Nerve & Muscle Blend by Red Moon Herbs
- Relaxed Mood Alcohol Free by Hawaii Pharm
- Diet-Phen by Source Naturals
- Relax by Custom Health Centers
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