is st john’s wort fda approved?

no. in the united states it is a dietary supplement under the 1994 dietary supplement health and education act, sold without fda review of efficacy, safety or potency, and never approved for depression or anything else. the fda’s one action on it was a public health advisory on february 10, 2000, after a national institutes of health study showed it cut blood levels of the hiv drug indinavir by more than half, warning that the same mechanism affects many other medicines. in germany and several other european countries standardised extracts are licensed prescription medicines.

what drugs does st john’s wort interact with?

many, because it induces the liver enzyme cyp3a4 and the transporter p-glycoprotein, which clear a large share of all drugs faster. documented examples: the hiv drug indinavir (exposure down 57% in volunteers, with the fda advisory that followed), cyclosporine (two heart-transplant rejections in 2000), alprazolam (exposure halved, half-life 12.4 to 6.0 hours), zolpidem (its label lists st john’s wort as reducing its effect), and the contraceptive pill (breakthrough bleeding and probable ovulation). the nih fact sheet also names amitriptyline, bupropion, phenytoin, carbamazepine, digoxin, ivabradine, nevirapine, irinotecan, imatinib, docetaxel, warfarin and simvastatin. taken with an ssri, snri, triptan, tramadol or maoi it can cause serotonin syndrome. the strength of the interaction depends on the product’s hyperforin content, which us supplements do not standardise.

can you take st john’s wort with an antidepressant?

the harvest records that taken with an ssri, snri, triptan, tramadol or maoi it adds serotonergic load and can precipitate serotonin syndrome, and the nih fact sheet says the same: taking it with drugs that affect serotonin "may lead to increased serotonin-related side effects, which can be serious". the trials that found it equivalent to ssris compared it with them, not on top of them. that is a question for the prescriber of the antidepressant, who needs to know it is being taken.

does st john’s wort make birth control fail?

it can. a cdc and fda systematic review found four studies of combined oral contraceptives taken with st john’s wort: three showed breakthrough bleeding, three showed reduced hormone exposure on pharmacokinetic measures, and one showed increased follicular growth and probable ovulation. none was large enough to measure pregnancy rates, so the failure rate is not known. the one product that showed no measurable effect was low in hypericin, and different products produced different degrees of interaction, so a negative result for one brand does not clear the others.

Supplement evidence

St John’s Wort

The depression trials, and the interaction list that makes it dangerous with other drugs.

page first published 2026-09-08 · last updated 2026-10-05

Not an FDA-approved treatmentSold as a dietary supplement5 studies on this page

What Its Legal Status Actually Means

Read this before anything below it. Legal to sell is not the same fact as reviewed, verified, or approved.

In the United States St. John's wort is sold as a dietary supplement under DSHEA, which means it reaches the shelf without FDA review of efficacy, safety, or potency and the FDA can act only after a problem emerges. It has never been FDA-approved to treat depression or anything else. The FDA issued a Public Health Advisory on 10 February 2000 warning that St. John's wort substantially lowered blood levels of the HIV drug indinavir through CYP3A4 induction and that the same mechanism would affect many other medicines. In Germany and several other European countries, by contrast, standardised hypericum extracts are licensed medicines that doctors prescribe for depression, which is why most of the trial evidence comes from German-speaking countries. Because US products are supplements rather than drugs, hypericin and hyperforin content varies widely between brands and batches — and hyperforin content is what drives the drug interactions, so two bottles labelled identically can behave very differently.

Quoted whole from the 2026-08-18 study harvest. Not summarized, not shortened.

does st john’s wort work for depression? what the trials, the fda and the interaction studies say

there is no fda label for st john’s wort, because in the united states it is sold as a dietary supplement and has never been reviewed for safety or effectiveness; in germany and several other european countries standardised extracts are licensed medicines. the regulatory facts below come from the legal-status paragraph above, written from the regulator’s documents in the 2026-08-18 study harvest, and from the nih fact sheet linked at the end; every trial figure is from a study record on this page or a paper cited by doi. every source is linked at the end of this section. last checked 2026-10-05.

st john’s wort, hypericum perforatum, is the one supplement on this site with a trial record that looks like a prescription antidepressant’s: dozens of double-blind trials, thousands of people, head-to-head comparisons with ssris in which it held its own. it is also the one supplement with an fda public health advisory, issued in february 2000 after a national institutes of health study showed it stripped more than half of an hiv drug out of the blood, and the same mechanism reaches transplant drugs, blood thinners, heart drugs, cancer drugs, benzodiazepines, sleeping pills and the contraceptive pill. this section covers the depression trials and the interaction record in both directions, with the funders named. every figure is from a study record on this page, a paper cited by doi, or a regulator document linked at the end.

this is information to take to a prescriber or pharmacist, and with this substance the pharmacist matters: the interactions below only get checked if the person taking it says so. nothing here tells anyone to take st john’s wort or to stop; stopping it abruptly while on an interacting drug can swing that drug’s level the other way.

what its legal status means, and does not mean

in the united states st john’s wort is sold as a dietary supplement under the 1994 dietary supplement health and education act, which means it reaches the shelf without fda review of efficacy, safety or potency, and the fda can act only after a problem emerges. it has never been fda-approved to treat depression or anything else [status]. the fda did act once: on february 10, 2000 it issued a public health advisory warning that st john’s wort substantially lowered blood levels of the hiv drug indinavir through induction of the liver enzyme cyp3a4, and that the same mechanism would affect many other medicines [status]. the study behind it, by the national institutes of health, is on this page [piscitelli-2000].

in germany and several other european countries standardised hypericum extracts are licensed medicines that doctors prescribe for depression, which is why most of the trial evidence comes from german-speaking countries [status]. because us products are supplements rather than drugs, hypericin and hyperforin content varies widely between brands and batches, and hyperforin is what drives the drug interactions, so two bottles labelled identically can behave very differently [status; nicolussi-2020]. the nih’s own fact sheet, updated in may 2025, says it "can weaken the effects of many medicines, including crucially important medicines" [nccih].

what the trials measured, in whom, and for how long

three syntheses carry the depression evidence. the cochrane review pooled 29 randomised double-blind trials in 5,489 people with major depression, against placebo and against standard antidepressants [linde-2008]. a rand corporation review, funded by the us department of defense, covered 35 trials in 6,993 people and graded each conclusion [apaydin-2016]. a 2017 meta-analysis pooled the 27 trials that compared st john’s wort head-to-head with an ssri, 3,808 people in all [ng-2017]. the interaction evidence is a different kind: pharmacokinetic studies in healthy volunteers [piscitelli-2000; markowitz-2003], case reports [ruschitzka-2000], a cdc and fda systematic review on contraceptives [berry-bibee-2016], a mechanistic review [nicolussi-2020], and the labels of the drugs it affects [ambien-label].

what was not measured. the trials were in mild to moderate depression and ran 4 to 12 weeks; there is essentially no research in severe depression, in people at high suicide risk, or over the long term [apaydin-2016; ng-2017; risks]. none of the efficacy trials was designed to detect rare harms, including the interactions that are st john’s wort’s main danger, and adverse events were poorly reported in them [apaydin-2016].

what the research says, in both directions

in favour. against placebo, hypericum extracts produced more responders, with a response rate ratio of 1.28 (95% ci 1.10 to 1.49) in the nine larger trials [linde-2008], and 1.53 (1.19 to 1.97) across 18 trials in 2,922 people in the rand review [apaydin-2016]. against standard antidepressants it was equivalent: rate ratio 1.00 (0.90 to 1.11) against ssris in 12 trials, with fewer people dropping out for side effects (odds ratio 0.53) [linde-2008]; 1.01 (0.90 to 1.14) with fewer adverse events (odds ratio 0.67, 0.56 to 0.81) [apaydin-2016]; and in the 27 head-to-head trials, response (0.983, 0.924 to 1.042) and remission (1.013, 0.892 to 1.134) indistinguishable from ssris, with fewer people stopping it (odds ratio 0.587, 0.478 to 0.697) [ng-2017]. the nih fact sheet summarises it the same way: "more effective than a placebo and as effective as standard antidepressant medications for mild or moderate depression" [nccih].

against, or smaller than the badge suggests. in the cochrane review the size of the advantage over placebo depended on the trial: 1.28 in the nine larger trials against 1.87 (1.22 to 2.87) in the nine smaller ones, a classic sign that small trials inflate the effect, and trials from german-speaking countries reported systematically more favourable results, which the authors say "complicates the interpretation" [linde-2008]. the rand review graded every conclusion only moderate quality because heterogeneity was severe (i-squared 79% to 89%) [apaydin-2016]. the head-to-head meta-analysis reports p-values below 0.001 beside confidence intervals that comfortably include 1.0, an internal inconsistency; the intervals show equivalence, not superiority, and the analysis did not assess drug interactions at all [ng-2017]. the nih fact sheet adds that it is "uncertain whether this is true for severe depression or for time periods longer than 12 weeks" [nccih]. and the harvest records that it can precipitate mania in people with bipolar disorder, causes photosensitivity, and may be unsafe in pregnancy [risks; nccih].

who paid. all three authors of the cochrane review disclosed financial relationships with schwabe, a hypericum manufacturer: a research grant and speaking fees for one, travel reimbursement for all three [linde-2008]. the rand review was funded by the us department of defense, which had no role in the analysis, and its own evidence tables record that a substantial share of the trials it pooled were industry-funded, had a manufacturer author or were supplied with the product [apaydin-2016]. the head-to-head meta-analysis’s funding could not be read [ng-2017]. three of the four authors of the mechanistic interaction review are employees of a st john’s wort manufacturer; note the direction of that interest, since authors paid by a maker nonetheless document the interactions [nicolussi-2020]. the contraceptive review was cdc intramural work; the alprazolam study was independently funded [berry-bibee-2016; markowitz-2003].

the interactions, which are the reason for this page

the mechanism is one thing doing many: st john’s wort activates the pregnane-x receptor, which switches on the liver enzyme cyp3a4 and the transporter p-glycoprotein, and both clear a long list of drugs faster. the degree of induction correlates with how much hyperforin the particular product contains [nicolussi-2020]. the first documented casualties were in 2000. in healthy volunteers, st john’s wort cut the exposure to the hiv protease inhibitor indinavir by a mean of 57% and its 8-hour trough by 81%, a reduction the authors said could lead to drug resistance and treatment failure [piscitelli-2000]; the fda’s advisory followed within weeks [status]. the same year, two heart-transplant patients on cyclosporine rejected their grafts after taking it [ruschitzka-2000].

the measured examples since. after 14 days of st john’s wort at 300 mg three times a day, alprazolam exposure halved and its half-life fell from 12.4 to 6.0 hours in 12 healthy volunteers; the authors noted that cyp3a4 substrates "represent at least 50% of all marketed medications" [markowitz-2003]. the zolpidem label lists st john’s wort with rifampin as an inducer that "may decrease effect" [ambien-label]. for the contraceptive pill, a cdc and fda systematic review found only four studies: three showed breakthrough bleeding, three showed reduced hormone exposure, and one showed follicular growth and probable ovulation, which is to say the pill may stop working; the one product with no measurable effect was a low-hypericin preparation, so a negative result for one brand does not clear the others, and none of the four studies could measure pregnancy rates [berry-bibee-2016]. the nih fact sheet names the classes: antidepressants (amitriptyline, bupropion), birth control pills, cyclosporine, the anti-seizure drugs phenytoin and carbamazepine, the heart drugs digoxin and ivabradine, the hiv drugs indinavir and nevirapine, the cancer drugs irinotecan, imatinib and docetaxel, warfarin, and simvastatin [nccih].

the other direction of risk. taken with an ssri, snri, triptan, tramadol or maoi, st john’s wort adds serotonergic load and can precipitate serotonin syndrome, so it is not something to layer on top of an antidepressant [risks; nccih]. and because it lowers the level of an interacting drug while it is being taken, stopping it abruptly can swing that drug’s level the other way, into toxicity [risks]. the practical consequence is the one the alprazolam authors drew: the prescriber of the other drugs usually does not know, because nobody asked [markowitz-2003].

questions for a prescriber or pharmacist about st john’s wort

each one comes from a warning or a study above. they are questions, not instructions; the answers depend on a history nobody here has.

here is everything i take, prescribed or not, including the pill. can you check each one against st john’s wort before i start or stop it?
i take an antidepressant, a triptan or tramadol. the harvest records serotonin syndrome with those combinations; is that a risk for me?
i take hormonal contraception. the studies found breakthrough bleeding and probable ovulation on the pill with st john’s wort; what backup would you want me to use?
the trials were 4 to 12 weeks in mild to moderate depression. where does my depression sit, and what would we do if it is more than that or lasts longer?
if i decide to stop taking it while on another drug, should the other drug’s dose or level be checked, given that the interaction runs in reverse when it stops?
the interaction strength depends on hyperforin content, which us products do not standardise. does the bottle i have say what it contains?
i have bipolar disorder, am pregnant, or burn easily in the sun. the harvest and the nih fact sheet flag each; does that change anything?

questions people ask

does st john’s wort work for depression?: in mild to moderate depression over 4 to 12 weeks, the trials say it beats placebo and matches ssris. the cochrane review of 29 double-blind trials in 5,489 people found more responders than placebo (rate ratio 1.28 in the larger trials) and equivalence to ssris (1.00) with fewer dropouts; a rand review of 35 trials found the same (1.53 against placebo, 1.01 against antidepressants, fewer adverse events); 27 head-to-head trials in 3,808 people found response and remission indistinguishable from ssris. the caveats are real: small trials and german-speaking trials reported bigger effects, the review authors had ties to a manufacturer, heterogeneity was severe, and there is essentially no evidence in severe depression, in people at high suicide risk, or beyond 12 weeks.
is st john’s wort fda approved?: no. in the united states it is a dietary supplement under the 1994 dietary supplement health and education act, sold without fda review of efficacy, safety or potency, and never approved for depression or anything else. the fda’s one action on it was a public health advisory on february 10, 2000, after a national institutes of health study showed it cut blood levels of the hiv drug indinavir by more than half, warning that the same mechanism affects many other medicines. in germany and several other european countries standardised extracts are licensed prescription medicines.
what drugs does st john’s wort interact with?: many, because it induces the liver enzyme cyp3a4 and the transporter p-glycoprotein, which clear a large share of all drugs faster. documented examples: the hiv drug indinavir (exposure down 57% in volunteers, with the fda advisory that followed), cyclosporine (two heart-transplant rejections in 2000), alprazolam (exposure halved, half-life 12.4 to 6.0 hours), zolpidem (its label lists st john’s wort as reducing its effect), and the contraceptive pill (breakthrough bleeding and probable ovulation). the nih fact sheet also names amitriptyline, bupropion, phenytoin, carbamazepine, digoxin, ivabradine, nevirapine, irinotecan, imatinib, docetaxel, warfarin and simvastatin. taken with an ssri, snri, triptan, tramadol or maoi it can cause serotonin syndrome. the strength of the interaction depends on the product’s hyperforin content, which us supplements do not standardise.
can you take st john’s wort with an antidepressant?: the harvest records that taken with an ssri, snri, triptan, tramadol or maoi it adds serotonergic load and can precipitate serotonin syndrome, and the nih fact sheet says the same: taking it with drugs that affect serotonin "may lead to increased serotonin-related side effects, which can be serious". the trials that found it equivalent to ssris compared it with them, not on top of them. that is a question for the prescriber of the antidepressant, who needs to know it is being taken.
does st john’s wort make birth control fail?: it can. a cdc and fda systematic review found four studies of combined oral contraceptives taken with st john’s wort: three showed breakthrough bleeding, three showed reduced hormone exposure on pharmacokinetic measures, and one showed increased follicular growth and probable ovulation. none was large enough to measure pregnancy rates, so the failure rate is not known. the one product that showed no measurable effect was low in hypericin, and different products produced different degrees of interaction, so a negative result for one brand does not clear the others.
what happens if you stop st john’s wort?: for the depression itself, the trials ran only 4 to 12 weeks and do not say. the interaction record does say something: while it is being taken it lowers the blood level of any interacting drug, so stopping it abruptly can swing that drug’s level the other way, into toxicity. anyone taking an interacting medicine, a transplant drug, warfarin, digoxin, an anti-seizure drug, an hiv drug, has a reason to involve the prescriber in stopping as well as starting.

sources for this section

the library rows link to our one-page summary of each study, with the original paper, its funding and our evidence grade on that page.

What the Research Shows

5 records from the 2026-08-18 harvest, each checked against PubMed and Europe PMC on that date. How a study was designed, how many people were in it, and who paid for it are printed above what it found, because those three facts decide how much the finding is worth.

Study 1 · 2008
- Meta-analysis of randomized trials
- 5,489 participants
- Top-tier journal
- Funding not established
- Preregistered
- Declared conflicts of interest
strong76/100
Well-supported by good-quality research.
Read this first: All three review authors disclosed financial relationships with Schwabe, a hypericum manufacturer: one had received a research grant and conference speaking fees, and all three had accepted travel reimbursement. The review itself flags that country of origin and trial size both predicted the result, which the authors say "complicates the interpretation" — plain language for probable bias in the underlying literature. The review is from 2008 and has not been updated.
Pooling 29 randomised double-blind trials in 5,489 patients with major depression, hypericum extracts beat placebo on response rate — but the size of the advantage depended on the trial: in the nine larger trials the response rate ratio was 1.28 (95% CI 1.10-1.49) versus 1.87 (95% CI 1.22-2.87) in the nine smaller ones, a classic sign that small trials inflate the effect. Against standard antidepressants it was equivalent (RR 1.00, 95% CI 0.90-1.11 versus SSRIs, 12 trials) and fewer people dropped out for side effects (OR 0.53 versus SSRIs). Trials from German-speaking countries reported systematically more favourable results.
Linde K, Berner MM, Kriston L. (2008). St John's wort for major depression. Cochrane Database of Systematic Reviews. PMID 18843608.
How this record was checked
PubMed record 18843608 fetched via NCBI efetch 2026-08-18; title, authors, journal, year, DOI (CD000448.pub3), the 29 trials / 5,489 patients count, and every effect estimate quoted above confirmed from the abstract, along with the verbatim conflict-of-interest statement naming Schwabe. Europe PMC core record checked 2026-08-18: no grant list; the Cochrane full text is not deposited (PMC7032678 returns abstract only via NCBI efetch and 404 on Europe PMC fullTextXML), so the Sources of Support section could not be read and funding is recorded UNKNOWN. Preregistered recorded true because Cochrane reviews are preceded by a published protocol and this version is an update of CD000448.pub2.
Study 2 · 2016
- Systematic review of randomized trials
- 6,993 participants
- Reputable journal
- Independently funded
- Preregistered
- Declared conflicts of interest
gold standard94/100
Top of the evidence hierarchy, independently funded.
Read this first: The review's own evidence tables record that a substantial share of the included trials were industry-funded, had a manufacturer author, or were supplied with the product by the manufacturer, and that funding was simply unreported for several others. The authors also note that adverse events were poorly reported in the source trials and that none of the studies was designed to detect rare harms — including the drug interactions that are St. John's wort's main danger.
A RAND Corporation review of 35 trials in 6,993 patients found St. John's wort produced more treatment responders than placebo (RR 1.53, 95% CI 1.19-1.97, from 18 RCTs in 2,922 people) and worked about as well as antidepressants in mild and moderate depression (RR 1.01, 95% CI 0.90-1.14) with fewer adverse events (OR 0.67, 95% CI 0.56-0.81). Every one of those conclusions was graded only moderate quality because heterogeneity was severe (I-squared 79-89%), and there is essentially no research in severe depression.
Apaydin EA, Maher AR, Shanman R, Booth MS, Miles JN, Sorbero ME, Hempel S. (2016). A systematic review of St. John's wort for major depressive disorder. Systematic Reviews. PMID 27589952.
How this record was checked
PubMed record 27589952 fetched via NCBI efetch 2026-08-18; title, all seven authors, journal, year, DOI, the 35 studies / 6,993 patients count, every effect estimate quoted above, and the PROSPERO registration CRD42015016406 confirmed from the abstract. Europe PMC core record and full text (PMC5010734) fetched 2026-08-18: the Funding section reads "The research was funded by the Department of Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury (DCoE). The funder had no role in the collection, analysis, and interpretation of the data" — hence funding INDEPENDENT — and the Competing Interests section reads "The authors declare that they have no competing interests."
Study 3 · 2017
- Meta-analysis of randomized trials
- 3,808 participants
- Reputable journal
- Funding not established
strong73/100
Well-supported by good-quality research.
Read this first: The abstract reports p<0.001 alongside pooled risk ratios whose 95% confidence intervals comfortably include 1.0, which is internally inconsistent; read the confidence intervals, which show equivalence rather than superiority. This meta-analysis also inherits the industry funding and country-of-origin biases present in the underlying trial literature, and it did not assess drug interactions at all.
Pooling 27 trials that compared St. John's wort head-to-head with SSRIs in 3,808 patients, response rates were statistically indistinguishable (RR 0.983, 95% CI 0.924-1.042) as were remission rates (RR 1.013, 95% CI 0.892-1.134), and fewer people stopped St. John's wort than stopped the SSRI (OR 0.587, 95% CI 0.478-0.697). Every included trial ran only 4 to 12 weeks, and the authors state it is unclear whether St. John's wort helps people with severe depression or high suicide risk.
Ng QX, Venkatanarayanan N, Ho CY. (2017). Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis. Journal of Affective Disorders. PMID 28064110.
How this record was checked
PubMed record 28064110 fetched via NCBI efetch 2026-08-18; title, authors, journal, year, DOI, the 27 trials / 3,808 patients count, and every effect estimate quoted above confirmed from the abstract. Europe PMC core record checked 2026-08-18: no grant list and no PMC full text available, so the funding statement could not be read and funding is recorded UNKNOWN.
Study 4 · 2016
- Systematic review of observational studies
- Reputable journal
- Independently funded
- Declared conflicts of interest
strong73/100
Well-supported by good-quality research.
Read this first: Only four eligible studies existed, none of them powered to measure pregnancy rates, so the evidence establishes a mechanism and a warning signal rather than a quantified failure rate. Different St. John's wort products produced different degrees of interaction, which means a negative result for one brand does not clear the others.
A CDC and FDA systematic review found only four studies comparing combined oral contraceptives alone with the same pills taken alongside St. John's wort, but three of the four showed breakthrough bleeding, three showed reduced hormone exposure on pharmacokinetic measures, and one showed increased follicular growth and probable ovulation — meaning the pill may stop working. The one product that showed no significant pharmacokinetic difference was a low-hypericin preparation.
Berry-Bibee EN, Kim MJ, Tepper NK, Riley HE, Curtis KM. (2016). Co-administration of St. John's wort and hormonal contraceptives: a systematic review. Contraception. PMID 27444983.
How this record was checked
PubMed record 27444983 fetched via NCBI efetch 2026-08-18; title, authors, journal, year, DOI, and the finding that 4 of 48 identified articles met inclusion criteria confirmed from the abstract; the record carries the statement "Conflicts of interest: none." Europe PMC core record fetched 2026-08-18 lists grant agency "Intramural CDC HHS" (grant CC999999), hence funding INDEPENDENT. Participant totals are not stated in the abstract, so sampleSize is left null rather than guessed.
Study 5 · 2020
- Narrative review
- Reputable journal
- Funding not established
- Declared conflicts of interest
contested32/100
Weak or heavily disputed. Treat as a question, not an answer.
Read this first: Three of the four authors are employees of Max Zeller Söhne AG, a manufacturer of a St. John's wort herbal medicinal product, and this is a narrative review rather than a systematic one — so it sits at the bottom of the evidence rubric and its framing should be read with the authors' commercial interest in mind. Note the direction of that interest: authors paid by an SJW manufacturer nonetheless document the interactions, which makes the interaction findings harder, not softer.
Twenty years after St. John's wort caused acute graft rejection in two heart transplant patients on cyclosporine, this review confirms the mechanism: St. John's wort activates the pregnane-X receptor, inducing CYP3A4 and P-glycoprotein, and so lowers blood levels of cyclosporine, tacrolimus, digoxin, indinavir, warfarin, alprazolam, simvastatin, and oral contraceptives. The degree of CYP3A4 induction correlates significantly with how much hyperforin the particular preparation contains, which is why interaction risk differs between products bearing the same name.
Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. (2020). Clinical relevance of St. John's wort drug interactions revisited. British Journal of Pharmacology. PMID 31742659.
How this record was checked
PubMed record 31742659 fetched via NCBI efetch 2026-08-18; title, authors, journal, year, and DOI confirmed. Europe PMC full text (PMC7056460) fetched 2026-08-18: the only declaration present is the conflict-of-interest statement "S.N., J.D., and V.B. are employees of a manufacturer of an SJW herbal medicinal product. H.M. has no conflict of interest to declare"; no funding statement exists in the article, so funding is recorded UNKNOWN and independent is recorded false on the strength of the employment disclosure.

The Risks

Nobody checks this purchase the way a prescription is checked. No prescriber reviews it against the rest of what you take, no pharmacist screens the interaction, and no regulator confirms the dose in the capsule before it is sold. That is why this section sits here at full length rather than as a footnote.

What the paragraph below covers:

Serotonin syndrome
Psychosis and mania
Drug interactions
Fertility and pregnancy
What is actually in the product
Skin reactions

St. John's wort is one of the most dangerous interacting substances sold over the counter, and its reputation as a gentle herbal alternative is the problem. It is a potent activator of the pregnane-X receptor and therefore induces CYP3A4 and P-glycoprotein, which lowers blood levels of a long list of drugs: cyclosporine and tacrolimus (two heart transplant patients rejected their grafts in 2000), HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors, warfarin, digoxin, simvastatin, alprazolam, some chemotherapy agents, anticonvulsants, and oral contraceptives — where the documented consequences are breakthrough bleeding, follicular growth and probable ovulation, i.e. unintended pregnancy. Taken with an SSRI, SNRI, triptan, tramadol, or MAOI it can add serotonergic load and precipitate serotonin syndrome, so it is not something to layer on top of an antidepressant, and stopping it abruptly while on an interacting drug can swing that drug's level the other way into toxicity. It also causes photosensitivity, can precipitate mania in people with bipolar disorder, and — because the trials that support it ran only four to twelve weeks in mild to moderate depression — there is no evidence for its use in severe depression, in people with high suicide risk, or over the long term. Because content is unregulated, the strength of both the antidepressant effect and the interaction risk varies by product.

What Is Not Known

The boundaries of the section above, in the harvest’s own words. What it excluded, why, and where it looked and found nothing. An absence of evidence is not evidence of absence, and it is not evidence of benefit either.

What Was Left Out, and Why

Quoted from the harvest, where these notes sat above the study list rather than after it. Where a note says “below” it means the studies in the section above.

Ng 2017 (PMID 28064110) is included, but note that its abstract reports p<0.001 for pooled risk ratios whose confidence intervals cross 1.0 (response RR 0.983, 95% CI 0.924-1.042); that is an internal reporting inconsistency and the finding text below reports the intervals, not the p-values.
Individual efficacy RCTs (Hypericum Depression Trial Study Group 2002, Szegedi 2005, Fava 2005 and others) excluded in favour of the pooled analyses below, which subsume them; the Apaydin evidence tables record that many of those trials were industry-funded or had industry authors.
Single case reports of serotonin syndrome, transplant rejection, and contraceptive failure excluded in favour of the interaction reviews below.
No verifiable PubMed-indexed record was found for a regulatory action document (FDA Public Health Advisory of 10 February 2000 on St. John's wort and indinavir) that could be confirmed end-to-end under this batch's verification protocol, so it is described in regulatory_status rather than entered as a study.

The Retraction Check

PubMed efetch records for all five PMIDs fetched 2026-08-18 and inspected for "Retraction in", "Erratum", "Expression of concern", and "Withdrawn" flags; none present. Europe PMC correction lists checked; none present.

Questions for a Prescriber or Pharmacist

This page does not tell anyone to take St John’s Wort or to avoid it. It is not able to: it does not know what else you take, what you have tried, or what you are treating. These are the questions each study above raises, written to be asked out loud.

The Cochrane evidence for St. John's wort is for mild-to-moderate major depression over a few weeks — does my depression fit that, and does St. John's wort interact with anything else I'm taking?
This review found St. John's wort works about as well as an antidepressant for mild to moderate depression but wasn't tested in severe depression — where does mine sit, and what would you recommend given that?
All the head-to-head studies of St. John's wort against SSRIs lasted twelve weeks or less — if I need treatment for longer than that, what do we actually know?
I take hormonal birth control — does St. John's wort make it less reliable for me, and if so what backup contraception should I be using?
Can you check every one of my prescriptions against St. John's wort — including anything I take for transplant, HIV, blood thinning, heart rhythm, or seizures — before I start or stop it?

And the one to ask at the counter, whatever the answers above turn out to be: given everything I am already taking, what would you want to know about St John’s Wort before I put it in the same body?

Open St John’s Wort in veisund

The app has the resources behind this page and people working through the same questions.What you post there goes to people, not to a model. If someone answers, it is a person who has been there. The one automated message is a crisis-resource reply.

Where This Page Comes From

Transcribed from the study-harvest-2026-08-18 record for st-johns-wort, built into this page by scripts/supplement-ingest.mjs on 2026-09-07. Nothing here is fetched at page load, and nothing here was written by a model without a citation behind it.

Source file	study-harvest/2026-08-18/st-johns-wort.yaml
Source repo	REPTechnologies/avalo-backend
SHA-256	1a415c0ca6f5e35dbf5b1cbcd5bd6bb6b28ba375366a8f9453242d8bdf035897
Also searched as	Hypericum perforatum, SJW, hypericum, Klamath weed, Tipton's weed, LI 160, WS 5570, STW3-VI, Ze 117

The Other Substances

Do any supplements actually work? asks the question across all of them. The full library has the medication records, the funding investigations, and the glossary.