St John's Wort (Hypericum perforatum)
St John's Wort is a yellow-flowered plant traditionally used for low mood. In the UK it has an unusual regulatory status: at higher strengths it is sold as an MHRA-registered Traditional Herbal Medicine (you'll see the THR licence number on the pack, and it can be marketed for "slightly low mood and slight anxiety"); at lower strengths it is sold as a food supplement with no health claim allowed. UK NHS treatment for diagnosed depression (NICE NG222) does NOT include St John's Wort — talking therapies and prescribed antidepressants are the pathway. Camden Medicals does NOT stock St John's Wort. The single most important thing to know about St John's Wort is its drug-interaction profile. It is one of the most-documented herb-drug interaction signals in clinical pharmacology — it speeds up how your body breaks down dozens of common medicines, making them work less well. This includes hormonal contraceptives (multiple pregnancies reported), transplant medicines (rejection risk), HIV medicines, warfarin, certain statins, certain antiepileptics, and some cancer treatments. Combined with most antidepressants, triptans for migraine, tramadol, or 5-HTP / L-tryptophan supplements it can trigger serotonin syndrome — potentially life-threatening. <strong>Critical: if you take ANY prescribed medicine, talk to your pharmacist or GP before starting St John's Wort.</strong> This is true even of the THR-registered traditional medicine version.
Camden Medicals editorial · Last reviewed 6 May 2026 · Next review November 2026
- Cross-checked against
- NHS
- NICE
- BNF
- EFSA
- FSA
Camden's editorial team independently graded each health claim below on the strength of the published evidence — see the grade beside every condition.
- Class
- Botanical
- Typical daily dose
- UK MHRA Traditional Herbal Registration (THR) products are registered at hyperforin/hypericin strengths corresponding to approximately 600-1800 mg/day of standardised extract. Trial materials in mild-to-moderate depression literature span the same range (LI-160, WS 5570, ZE 117, STW3-VI). Lower-strength food-supplement St John's Wort is sold without a UK health claim and is not directly comparable to trial materials.
- Top use evidence
- Strong
On this page
What it is
St John's Wort is a yellow-flowered plant traditionally used across Europe for hundreds of years for low mood. The name comes from the flowering time around St John the Baptist's feast day in late June.
In the UK it sits in a regulatory grey area that's worth understanding before you research it further:
Registered Traditional Herbal Medicines (THR) — higher-strength St John's Wort sold under the MHRA's Traditional Herbal Registration scheme. You'll see "THR" followed by a product licence number on the pack (e.g. Karpaz, Arkocaps, A. Vogel Hyperiforce). These can be marketed for "the symptomatic relief of slightly low mood and slight anxiety, based on traditional use only." Critically, the THR scheme does NOT require evidence the product works — it confirms safety, quality, and traditional-use history. The "based on traditional use only" wording is mandatory.
Food-supplement St John's Wort — lower-strength versions sold as food supplements without an MHRA licence. These cannot make any UK health claim about mood or anxiety. They typically have lower hyperforin / hypericin content than THR products.
Both forms carry the same drug-interaction profile and the same prescriber-disclosure rule.
A note on what's IN St John's Wort: the two compounds that get blamed for most of the effects are hyperforin (responsible for the mood activity AND the drug interactions) and hypericin (responsible for the sun-sensitivity reaction at higher doses). Standardised extracts on UK shelves declare percentages of one or both. Generic dried herb at the same milligram delivers quite different content from a standardised extract — most of the clinical trial evidence used specific standardised extracts (LI-160, WS 5570, ZE 117, STW3-VI), not generic powder.
Camden does not stock St John's Wort in any form. This entry is the reference for anyone researching it — particularly because so many other supplements (5-HTP, L-tryptophan, ginseng, ginkgo) reference St John's Wort as the canonical "always check with your pharmacist first" example.
At a glance
- Sold in the UK in two forms — registered Traditional Herbal Medicine (look for "THR" + product licence number) at higher strengths, OR food supplement at lower strengths with no health claim allowed. Camden does NOT stock either.
- CRITICAL drug-interaction profile — affects most common prescribed medicines. If you take any prescribed medication, talk to your pharmacist or GP BEFORE starting. The MHRA has issued repeated safety alerts on this.
- Reduces effectiveness of hormonal contraception (combined pill, mini-pill, implant, emergency contraception). Pregnancies have been reported. Additional barrier contraception required during use AND for ≥4 weeks after stopping. IUDs (copper, Mirena) are not affected.
- Do NOT combine with prescribed antidepressants (SSRIs, SNRIs, tricyclics, MAOIs), triptans for migraine, tramadol, lithium, or supplements like 5-HTP and L-tryptophan — serotonin syndrome risk.
- Do NOT use if you take transplant medicines (ciclosporin, tacrolimus), HIV antiretrovirals, warfarin, or named cancer treatments — risk of treatment failure or rejection.
- NOT recommended in pregnancy or breastfeeding. Talk to your midwife or GP. NHS pathway for diagnosed depression is NICE NG222 — talking therapies and/or prescribed antidepressants.
- Stop St John's Wort ≥7-10 days before any planned surgery.
- Can cause sun-sensitivity at higher doses — avoid prolonged sun exposure and sunbeds.
What people use it for
Adults considering St John's Wort for slightly low mood or slight anxiety
MHRA-registered THR products may be marketed in the UK for "the symptomatic relief of slightly low mood and slight anxiety, based on traditional use only". The THR registration does NOT require efficacy evidence — it confirms safety, quality, and traditional use. If you take prescribed medication of any kind (including hormonal contraception), talk to your pharmacist or GP before starting St John's Wort. Do not start it the week before planned surgery. [6]
Some evidenceLimitedAdults with diagnosed moderate or severe depression
St John's Wort is not a UK-recognised pathway for diagnosed depression. UK NICE NG222 (Depression in adults: treatment and management) sets out the NHS pathway — talking therapies, antidepressant medication, or both, depending on severity. Self-supplementing with St John's Wort instead of NHS treatment for moderate or severe depression is not appropriate. Your GP can refer you to talking therapies via NHS Talking Therapies (formerly IAPT); waits vary but the front door is open. [2,13]
Popular, not provenInsufficientAdults already taking prescribed medication of any kind
Do NOT start St John's Wort without first checking with your prescribing pharmacist or GP. The list of medicines St John's Wort interacts with is long — hormonal contraceptives, antiretrovirals, ciclosporin, warfarin, digoxin, certain statins, several antiepileptics, several anti-cancer drugs, and most antidepressants. The interaction is mediated by CYP3A4 and P-glycoprotein induction and develops over 10-14 days of regular use. The MHRA has issued multiple Drug Safety Updates on this. [1,2]
Some evidenceStrongPregnant or breastfeeding women, or women trying to conceive
Avoid St John's Wort. Safety in pregnancy and lactation is not established; the MHRA THR product literature lists pregnancy and breastfeeding as contraindications. Women using hormonal contraception who are taking St John's Wort should not assume contraceptive efficacy — additional barrier contraception or a different supplement is required during use and for at least 4 weeks after stopping. [1]
Some evidenceStrongAdults considering St John's Wort alongside 5-HTP, L-tryptophan, or other serotonergic supplements
Do not stack. St John's Wort and serotonin-precursor supplements (5-HTP from Griffonia, L-tryptophan) act on the serotonergic system through different mechanisms; combining them stacks serotonergic load and can precipitate serotonin syndrome (agitation, tremor, sweating, hyperthermia, tachycardia, in severe cases hyperthermia and rhabdomyolysis). The same warning applies to combination with SSRIs, SNRIs, triptans, tramadol, pethidine, MAOIs, lithium, and dextromethorphan. [1,2]
Some evidenceStrong
How it works
St John's Wort does three different things in the body at the same time, and the drug interactions come from one of them.
First, it changes how the brain handles mood chemistry. Hyperforin (the main active compound) slows down how quickly nerve cells reabsorb serotonin, noradrenaline, and dopamine — the same general idea behind many prescribed antidepressants, though St John's Wort works on a broader set of mood chemicals than most SSRIs. This is why combining St John's Wort with an SSRI or other serotonin-affecting medicine can stack the effect and tip into serotonin syndrome — a serious overload condition.
Second, and this is the part that drives the drug-interaction profile, hyperforin tells the liver to speed up production of its drug-breakdown enzymes (specifically a family called CYP3A4 and CYP2C9) and a separate cell-level pump (called P-glycoprotein) that pushes drugs out of cells. After about 10-14 days of taking St John's Wort regularly, the liver is breaking down many common medicines significantly faster than normal. This means a regular dose of those medicines reaches a lower level in the bloodstream and works less well — sometimes dramatically less well. Hormonal contraceptives are the most-publicised example; transplant medicines, HIV antiretrovirals, warfarin, and certain cancer treatments are also affected. The effect takes 10-14 days to build up and another 10-14 days to fade after stopping — pausing for a weekend does not reset it.
Third, hypericin (the other main compound) makes skin slightly more sensitive to UV light at higher doses. Pale-skinned users at THR-strength dosing are most affected — sunburn or rash on sun-exposed skin is the typical presentation.
Common myths
Myth""St John's Wort is natural therefore safe.""
RealityNaturalness-as-safety arguments do not apply here. St John's Wort has one of the most extensive herb-drug interaction profiles in clinical pharmacology — affecting hormonal contraceptives, transplant immunosuppressants, antiretrovirals, warfarin, certain statins, several antiepileptics, and many anti-cancer drugs. The MHRA has issued repeated Drug Safety Updates on this. "Natural" does not mean "interaction-free" and does not exempt a supplement from the same prescriber-disclosure rules that apply to a prescribed medicine. [1]
Myth""My contraceptive pill is fine with St John's Wort because they're both daily.""
RealityNo. St John's Wort induces CYP3A4 and reduces plasma levels of the synthetic oestrogens and progestogens in combined and progestogen-only contraceptives. Multiple pregnancies in women using both have been reported and the MHRA reissued its Drug Safety Update on this in 2014. Women taking hormonal contraception who choose to start St John's Wort require additional barrier contraception during use and for at least 4 weeks after stopping. This applies to combined pill, progestogen-only pill, etonogestrel implant, and ulipristal acetate emergency contraception. The intrauterine devices (copper and Mirena IUS) are not affected. [1]
Myth""St John's Wort is a UK-licensed treatment for depression.""
RealityIt is not. MHRA Traditional Herbal Registration (THR) products may be marketed for "the symptomatic relief of slightly low mood and slight anxiety, based on traditional use only" — the THR scheme registers products on traditional use, not on efficacy evidence. UK NICE NG222 is the depression treatment pathway, and St John's Wort is not in it. Marketing implying clinical equivalence to NHS-prescribed antidepressants is not supported by THR registration scope. [2]
Myth""I can switch from my SSRI to St John's Wort the next day.""
RealityNo. Both St John's Wort and SSRIs are serotonergic; combining or rapidly switching between them stacks serotonergic load and can precipitate serotonin syndrome. Wash-out periods (typically 1-2 weeks for short-half-life SSRIs, longer for fluoxetine) are required between SSRI and St John's Wort in either direction. Any switch should be planned with the prescribing GP or pharmacist — not unilaterally. [1]
Myth""I can pause St John's Wort for a few days and my drug interactions will reset.""
RealityThe CYP3A4 / P-gp induction takes 10-14 days to develop and approximately the same time to resolve after stopping. Pausing for a weekend does not undo the induction effect; conversely, starting and stopping cyclically does not protect interacting medicines. The MHRA recommendation for women on hormonal contraception is additional barrier contraception during use and for at least 4 weeks after stopping. [1]
What people say online
St John's Wort is one of the most-searched herbal-medicine clusters on TikTok and Reddit, often under the framing "natural Prozac" or "natural antidepressant for mild depression." UK consumer discourse is materially harmed by US-clinic content that ignores the UK drug-interaction safety framework and by lifestyle-influencer content that treats St John's Wort as interchangeable with SSRIs. The MHRA has issued repeated Drug Safety Updates on this — most prominently for hormonal contraceptive failure, which is the highest-volume UK consumer-safety concern. This section surfaces the discourse without naming individuals.
Trending claims
- TikTok + Instagram (wellness content)high visibility
Claim: Natural Prozac — works the same way, no side effects
Reality check: Partial overlap on mechanism (both affect serotonin reuptake) but the framing is misleading. UK MHRA Traditional Herbal Registration permits "slightly low mood / slight anxiety, based on traditional use only" — not equivalence to a prescribed antidepressant. UK NICE NG222 does NOT include St John's Wort in the depression treatment pathway. "Natural" does not mean "no side effects" — St John's Wort has one of the most documented drug-interaction profiles in herbal pharmacology. Talk to your pharmacist or GP before starting anything for low mood, especially if you take other medication. [8]
- TikTok + Reddithigh visibility
Claim: My contraceptive pill is fine with St John's Wort — they're both daily
Reality check: NO — this is one of the highest-priority MHRA Drug Safety warnings on St John's Wort. The herb induces the liver enzymes that break down hormonal contraceptives, reducing their effectiveness. Multiple pregnancies in women using both have been reported and the MHRA has reissued its Drug Safety Update on this multiple times. If you take ANY hormonal contraception (combined pill, mini-pill, implant, emergency contraception), you MUST use additional barrier contraception during St John's Wort use AND for ≥4 weeks after stopping. IUDs (copper, Mirena) are not affected.
- TikTok (anti-antidepressant content)medium visibility
Claim: Switch from your SSRI to St John's Wort to avoid side effects
Reality check: DANGEROUS. Both St John's Wort and SSRIs are serotonergic; rapidly switching between them stacks serotonergic load and can trigger serotonin syndrome — a potentially life- threatening condition. A medically-supervised switch requires a wash-out period (typically 1-2 weeks for most SSRIs, longer for fluoxetine). NEVER make this switch unilaterally — talk to your GP or prescribing pharmacist. The UK NICE NG222 pathway has options for managing SSRI side effects without involving St John's Wort. [9]
- TikTok + biohacker contentmedium visibility
Claim: It's only an issue with prescription drugs — supplements are fine to mix
Reality check: False. St John's Wort interacts with several common supplements as well, particularly 5-HTP (from Griffonia extract) and L-tryptophan — both serotonin precursors. Combining them stacks serotonergic load and risks serotonin syndrome. If you take any "mood support" supplement, talk to your pharmacist before adding St John's Wort.
Where the conversation lives
- TikTok hashtags: #stjohnswort, #naturalantidepressant, #moodsupplement, #herbsformood
- Reddit subs: r/Supplements, r/Nootropics, r/herbalism, r/Anxiety
- Forums: Examine.com (paid evidence analysis), MumsNet contraception threads
Questions people are searching
- Does St John's Wort actually work for depression?
- Is St John's Wort safe with the pill?
- Can I switch from sertraline to St John's Wort?
- How long until St John's Wort starts working?
- Is St John's Wort an MAOI?
Who drives the discourse: The discourse is driven by three influencer classes: wellness / herbalism creators (highest reach but variable evidence- anchoring; frequent "natural Prozac" framing); pharmacy / clinical pharmacology creators (more accurate on the drug- interaction profile + UK regulatory framework); and patient- advocacy creators (mix of personal-experience accounts + sceptical reframing of antidepressant medication). Verifera editorial does not name individuals.
Social-media trends change quickly. This section is editorial commentary on what people are searching for — not a recommendation.
Common online questions
Synthesised from the questions UK shoppers most often ask online about St John's Wort (Hypericum perforatum). Each answer is editorial and links to its evidence in the Sources list below.
Why is St John's Wort sold over the counter in the UK if it has so many drug interactions?
The MHRA Traditional Herbal Registration scheme allows traditional-use registration based on safety and quality (not efficacy). Higher-strength St John's Wort is sold in the UK as a registered THR herbal medicine carrying drug-interaction warnings on the label. Lower-strength food supplements without THR registration cannot make any UK health claim. The interaction profile is real and well-documented; the MHRA's position is that a clearly-labelled traditional-use product with explicit prescriber-disclosure language is a legitimate consumer choice for slightly low mood, but anyone on prescribed medication must check with their pharmacist or GP first. [6]
I take the combined pill — can I take St John's Wort?
Talk to a pharmacist or GP before starting it. The MHRA's Drug Safety Update specifically warns that St John's Wort can reduce the effectiveness of hormonal contraception and has been associated with multiple reported pregnancies. If you choose to take both, additional barrier contraception is required during use and for at least 4 weeks after stopping. The same applies to the progestogen-only pill and the etonogestrel implant. Intrauterine devices (copper coil, Mirena IUS) are not affected. [1]
I take warfarin — can I take St John's Wort?
Not without anticoagulation-clinic input. St John's Wort induces CYP2C9 and reduces warfarin's anticoagulant effect — INR drops, and clotting risk rises. Stopping St John's Wort while still on warfarin can cause INR to swing the other way. Tell your anticoagulation team about any St John's Wort use, including starting and stopping. [5,1]
I take ciclosporin after a transplant — can I take St John's Wort?
No. St John's Wort substantially reduces ciclosporin plasma levels (and the same applies to tacrolimus, sirolimus, and everolimus). Multiple cases of organ rejection in transplant recipients who started St John's Wort have been reported. Do not start it; if you are on it, tell your transplant team immediately. [1]
I take an HIV antiretroviral — can I take St John's Wort?
No. St John's Wort substantially reduces plasma levels of protease inhibitors (indinavir, ritonavir-boosted regimens) and non-nucleoside reverse-transcriptase inhibitors. The interaction risks treatment failure and the development of viral resistance. Disclose any supplement use to your HIV team. [1]
How long after stopping St John's Wort is it safe to start a serotonergic antidepressant?
That is a prescriber decision — typically a wash-out of 1-2 weeks is recommended but it depends on the specific antidepressant, the dose and duration of St John's Wort use, and the clinical urgency. Talk to the GP planning the switch. [1]
⚖️ The official position
What may lawfully be claimed about St John's Wort (Hypericum perforatum) in Great Britain. This is a regulatory position, not an evidence grade.
No health claim is authorised for this use in Great Britain.
St John's Wort (Hypericum perforatum) has a history of traditional use. Authorised health claims require a positive EFSA scientific opinion; none has been issued for this use.
UK regulatory landscape
UK regulatory tier: Food supplement
St John's Wort sits across two UK regulatory tiers depending on strength. Higher-strength preparations are registered under the MHRA Traditional Herbal Registration (THR) scheme — these carry a THR product licence number, can be marketed for "the symptomatic relief of slightly low mood and slight anxiety, based on traditional use only," and carry mandatory drug- interaction warnings. The THR scheme requires safety + quality + traditional-use evidence but does NOT require modern efficacy evidence. Lower-strength preparations are sold as food supplements under the UK Food Supplements (England) Regulations 2003 and carry NO authorised UK health claim. EFSA's evaluation of mood-related botanical claims remains on hold; claims may be presented as "on hold" but NOT as authorised.
What crosses the tier
| Condition | Crosses to |
|---|---|
| Marketing as a treatment for diagnosed depression, severe depression, anxiety disorders, bipolar disorder | Crosses to medicinal-product claims; outside THR scope; outside UK NICE NG222 / CG113 pathways; ASA / CAP Code §15 enforcement; MHRA Borderline Section may classify as a medicinal product requiring full product licence. |
| Marketing alongside SSRI antidepressants or 5-HTP / L-tryptophan without explicit do-not-combine warnings | Patient-safety event risk (serotonin syndrome). Failure to provide drug-interaction warning is outside THR labelling rules. |
| Marketing as suitable in pregnancy or breastfeeding | Outside UK MHRA THR product information; outside precautionary universal-avoidance position. |
| Higher-strength preparation marketed without THR registration | MHRA Borderline Section may classify as an unlicensed medicinal product; market-removal risk. |
Permitted claims
THR-registered products: "the symptomatic relief of slightly low mood and slight anxiety, based on traditional use only" — EXACT wording with the traditional-use qualifier. Food- supplement St John's Wort: no UK health claim permitted. Mandatory: drug-interaction warning on label. NOT permitted: "natural antidepressant," clinical-equivalence framing, pregnancy-safe claims, mood-boost / depression-cure framing.
Cross-jurisdiction note
St John's Wort regulation varies internationally. Germany has prescription-strength preparations (Jarsin, Neuroplant) used in mainstream psychiatric practice for mild-to-moderate depression. The US sells it widely as an over-the-counter dietary supplement under DSHEA with weaker warning requirements. UK consumers should not assume US or German clinic practice translates to the UK regulatory or safety framework.
UK regulatory rules evolve. This summary is editorial — businesses should consult regulatory counsel; consumers should consult their pharmacist or GP.
🔬 Camden’s evidence review
The research Camden reviewed, graded on its strength. This is our own appraisal — it sits beneath the official guidance above, never above it.
Mild-to-moderate depression — short-term trials of standardised extracts
MixedEvidencemixedMultiple short-term RCTs of specific standardised extracts (LI-160, WS 5570, ZE 117, STW3-VI) at hyperforin doses around 600-1800 mg/day extract have reported similar response rates to SSRI comparators in mild-to-moderate depression. A 2008 Cochrane systematic review (Linde et al.) concluded the extracts tested were "superior to placebo" and "similarly effective as standard antidepressants" in major depression but flagged substantial heterogeneity between trials and study quality limitations. Trial results are concentrated on specific standardised extracts — whole-herb powder and undeclared-strength supplements are not directly comparable to trial materials. UK NICE NG222 does not list St John's Wort in the depression treatment pathway. [14,2,15,16]
Severe depression
InsufficientEvidenceinsufficientTrial evidence does not support St John's Wort for severe depression. The Hypericum Depression Trial Study Group (2002, JAMA) compared LI-160 against placebo and sertraline in moderate-to-severe depression and found St John's Wort no better than placebo on the primary outcomes; sertraline was also non-superior on the primary outcome but separated on secondary outcomes. UK NHS treatment for severe depression is via NICE NG222 — talking therapies, antidepressant medication, or both. [2]
Anxiety, OCD, somatoform disorders, premenstrual syndrome, ADHD, smoking cessation, menopausal symptoms
InsufficientEvidenceinsufficientVarious small RCTs have explored St John's Wort across these indications. Evidence quality and trial size are not sufficient to support clinical use. UK NHS pathways apply for each diagnosis — anxiety (NICE CG113), OCD (CG31), ADHD (NG87), smoking cessation (NG209), menopause (NG23). St John's Wort is not in any of these pathways. [3,17]
Drug-interaction effect — CYP3A4 / P-gp induction
StrongEvidencestrongMultiple controlled pharmacokinetic studies in healthy volunteers and case-control studies have established that St John's Wort substantially induces CYP3A4, CYP2C9, and P-glycoprotein. Effect sizes are large enough to reduce plasma levels of co-administered substrate medicines by 30-60% in many cases — clinically meaningful for narrow-therapeutic-index drugs (ciclosporin, warfarin, digoxin, antiretrovirals) and for drugs whose efficacy depends on a minimum plasma level (oral contraceptives, anti-cancer agents). The MHRA Drug Safety Update for St John's Wort is the canonical UK prescribing reference. [1,2,18,19,20]
Effect matrix — per-condition evidence
Per-outcome summary of the published trial corpus: dose ranges studied, duration, evidence grade, and direction of effect. Each row is a citable claim.
| Outcome | Population | Dose | Duration | Evidence | Direction | Sources |
|---|---|---|---|---|---|---|
| Mild-to-moderate depression | adults | 500–1800 mg | 4–12 wk | ModerateEvidencemoderate | improvement | PMID 15846605 PMID 27589952 PMID 8704532 PMID 40014460 |
| Cochrane Linde 2008 meta-analysis. Response-rate ratio 1.15 (95% CI 1.02-1.29) vs placebo in larger major-depression trials; 1.71 (95% CI 1.40-2.09) in non-major-depression trials. Effect comparable to SSRIs (RR 0.98). Trial heterogeneity in extract type (LI-160, WS 5570, ZE 117, STW3-VI) limits between-product generalisability. UK NICE NG222 does not recommend. | ||||||
| Severe (major) depression | adults | 900–1800 mg | 6–12 wk | InsufficientEvidenceinsufficient | no change | PMID 15846605 |
| Hypericum Depression Trial Study Group 2002 JAMA negative on primary outcome in severe major depression (cited within the Linde Cochrane review). Larger, better-powered trials show progressively smaller effects — moderate-extract benefit does not extend to severe depression. Severe depression is a specialist-managed indication; NHS GP referral pathway applies. | ||||||
| CYP enzyme induction (drug-interaction signal) | general | 300–1800 mg | 2 wk | StrongEvidencestrong | decrement | PMID 20829645 PMID 12392581 PMID 18537576 PMID 11673747 PMID 11180019 PMID 31742659 |
| "Decrement" framing reflects the clinical-pharmacology signal: induction of CYP3A4 / CYP2C9 / P-glycoprotein reduces plasma levels of co-prescribed medicines — hormonal contraception, anticoagulants (warfarin), antiretrovirals, transplant immunosuppressants, many SSRIs (serotonin-syndrome risk also). Canonical UK BNF interaction profile; pharmacist consultation MANDATORY before starting if on any prescription medicine. | ||||||
Evidence grades follow the editorial convention: strong > moderate > limited > very_limited > insufficient. Direction reports the trial corpus consensus (improvement / no_change / mixed / decrement). Schema cross-emitted at MedicalSubstance.relevantClinicalCondition[].
Clinical literature review
St John's Wort has one of the larger herbal-medicine RCT bodies in clinical pharmacology — the Linde 2008 Cochrane systematic review (PMID 15846605) pulled together 37 trials including 26 placebo comparisons and 14 head-to-head comparisons with standard antidepressants. The conclusion: in mild-to-moderate depression, standardised extracts (LI-160, WS 5570, ZE 117, STW3-VI at hyperforin doses around 600-1800 mg/day) produced response rates comparable to SSRIs and superior to placebo, with lower side-effect-related dropout than older antidepressants. The signal is weaker for major depression and essentially absent for severe depression. The Schellander & Donnerer 2010 Pharmacology review (PMID 20829645) covers the drug-interaction side — the same CYP3A4 / CYP2C9 / P-glycoprotein induction profile that gives St John's Wort its drug-interaction footprint also limits its real-world prescribability. UK NICE NG222 has not adopted St John's Wort into the depression pathway, citing the heterogeneity in trial extracts and the drug-interaction risk.
Key trials
Linde K et al. · 2008 · Cochrane Database Syst Rev · PMID 15846605
Finding: 37 trials of hypericum extracts for depressive disorders. For major depression in larger trials: response-rate ratio 1.15 (95% CI 1.02-1.29) vs placebo. For non-major-depression trials: response-rate ratio 1.71 (95% CI 1.40-2.09) vs placebo. Hypericum extracts were similarly effective to SSRIs (RR 0.98) and tri/tetracyclic antidepressants (RR 1.03). Hypericum users dropped out for adverse effects less often than those on older antidepressants (OR 0.25, 95% CI 0.14-0.45).
Relevance: The largest published evidence synthesis on St John's Wort for depression. Heterogeneity between extracts and trial quality limits generalisability — different products deliver different hyperforin / hypericin content.
Schellander R, Donnerer J · 2010 · Pharmacology · PMID 20829645
Finding: Reviews clinically relevant interactions for antidepressants including SSRIs and St John's Wort. Confirms St John's Wort as the canonical CYP-enzyme-inducing herbal medicine with extensive drug-interaction footprint affecting hormonal contraception, transplant immunosuppressants, antiretrovirals, warfarin, and many other commonly co-prescribed medicines. Notes the gap between potential interactions and observed adverse events but emphasises specifying-prescriber-disclosure rule.
Relevance: Standard pharmacology reference cited in UK BNF and prescribing materials for the St John's Wort drug- interaction profile.
Systematic reviews
- pmid:15846605
Linde 2008 Cochrane meta-analysis. Hypericum extracts show small response advantage over placebo in mild-to- moderate depression and comparable efficacy to standard antidepressants in larger trials. UK NICE NG222 has not included St John's Wort in the depression pathway.
Evidence quality summary
Mild-to-moderate depression — MODERATE certainty (Linde 2008 Cochrane meta-analysis n=37 trials of standardised extracts). Severe depression — INSUFFICIENT certainty (Hypericum Depression Trial Study Group 2002 JAMA negative on primary outcome). Anxiety, OCD, premenstrual syndrome, ADHD, menopause — INSUFFICIENT certainty (small trials, no UK NICE pathway). Drug interactions — HIGH certainty (multiple controlled pharmacokinetic studies + repeated MHRA Drug Safety Updates). Pregnancy / lactation — INSUFFICIENT data; precautionary universal avoidance under UK MHRA THR product information.
Known gaps
- Different standardised extracts deliver different hyperforin / hypericin content; head-to-head comparison RCTs between extracts are limited.
- Whole-herb powder vs standardised-extract efficacy comparison sparse.
- Long-term safety data (>12 months) limited.
- Pregnancy-exposure outcome data essentially absent (precautionary universal avoidance limits controlled trials).
- UK-specific trial data limited — most trials are German or US.
This summarises the published evidence as of the last review date — it is not advice for your specific situation. Talk to your pharmacist or GP.
Safety
St John's Wort is one of the most clinically significant herb-drug interaction signals in pharmacology. If you take any prescribed medication — particularly hormonal contraception, antiretrovirals, transplant medication, warfarin, or antidepressants — talk to your pharmacist or GP before starting it.
Talk to your pharmacist or GP first if you:
- You take a hormonal contraceptive (combined pill, progestogen-only pill, etonogestrel implant, ulipristal acetate emergency contraception) — efficacy is reduced.
- You take an antidepressant (SSRI, SNRI, tricyclic, MAOI), a triptan, tramadol, pethidine, lithium, dextromethorphan, or another serotonergic medication — risk of serotonin syndrome.
- You take 5-HTP, L-tryptophan, or SAM-e supplements — risk of serotonin syndrome on combination.
- You take ciclosporin, tacrolimus, sirolimus, or everolimus (transplant immunosuppression) — transplant rejection risk.
- You take an HIV antiretroviral (protease inhibitor, NNRTI) — HIV treatment failure risk.
- You take warfarin or another anticoagulant — INR destabilisation; bleeding/clotting risk.
- You take digoxin — reduced digoxin plasma level, possible heart-failure decompensation.
- You take an antiepileptic (carbamazepine, phenytoin, perampanel, lamotrigine) — reduced antiepileptic plasma levels.
- You take an anti-cancer drug (imatinib, irinotecan, dasatinib, vinca alkaloids, taxanes) — chemotherapy failure risk.
- You take a statin (atorvastatin, simvastatin, lovastatin) — reduced cholesterol-lowering effect.
- You take a calcium-channel blocker, an oral diabetes medicine, or a PPI — possible reduced effect.
- You are pregnant, breastfeeding, or trying to conceive — avoid.
- You have planned surgery in the next two weeks — stop ≥7-10 days before because of perioperative bleeding and anaesthesia interactions.
Common side effects: GI upset, dry mouth, mild headache, photosensitivity rash on sun-exposed skin, restlessness, sleep disturbance.
Pregnancy and breastfeeding
NOT recommended in pregnancy. Safety has not been established and the MHRA Traditional Herbal Registration product literature lists pregnancy as a contraindication. Women using hormonal contraception who are taking St John's Wort cannot rely on contraceptive effectiveness — multiple pregnancies have been reported. Talk to your midwife or GP if you are pregnant or planning conception.
NOT recommended in breastfeeding. Small studies have detected hyperforin and hypericin in breast milk; infant safety is not established. Talk to your midwife or GP.
Talk to your GP, midwife, or pharmacist before starting any supplement during pregnancy or breastfeeding.
More clinical detail (for clinicians and informed readers)
Contraindications
- Diagnosed bipolar disorder — risk of mania induction.
- Concurrent serotonergic medication (SSRI, SNRI, tricyclic, MAOI, triptan, tramadol, pethidine, linezolid, lithium, dextromethorphan).
- Concurrent ciclosporin, tacrolimus, sirolimus, or everolimus.
- Concurrent HIV protease inhibitor or NNRTI.
- Concurrent warfarin or other vitamin-K-antagonist anticoagulants.
- Pregnancy, breastfeeding, planning conception.
- Children and adolescents under 18 — outside UK NICE pathways for paediatric depression (NG134).
- Diagnosed moderate or severe depression — outside UK NICE pathway (NG222).
- Planned surgery within ≤2 weeks.
Drug interactions
Hormonal contraception (combined pill, mini-pill, etonogestrel implant, ulipristal acetate emergency contraception, transdermal patch, vaginal ring) · high
Effect: REDUCED CONTRACEPTIVE EFFECTIVENESS. Multiple pregnancies in women using both have been reported and the MHRA has issued repeated Drug Safety Updates on this. IUDs (copper coil, Mirena IUS) are NOT affected.
Mechanism: St John's Wort induces the liver enzymes (CYP3A4) and the cellular pump (P-glycoprotein) that break down synthetic oestrogens and progestogens, lowering blood levels of the contraceptive hormones.
Action: Talk to your pharmacist or GP BEFORE starting St John's Wort if you use any hormonal contraception. If you choose to take both, additional barrier contraception is required during use AND for ≥4 weeks after stopping.
Source: MHRA Drug Safety Update + BNF St John's Wort
Antidepressants (SSRIs, SNRIs, tricyclics, MAOIs, bupropion) + triptans for migraine + tramadol + lithium + 5-HTP + L-tryptophan · high
Effect: Risk of SEROTONIN SYNDROME — a potentially life-threatening reaction (agitation, sweating, tremor, fever, fast heart rate, in severe cases organ failure). Combining or rapidly switching between St John's Wort and any of these serotonergic agents is DANGEROUS.
Mechanism: Both St John's Wort and serotonergic medicines increase serotonin signalling in the brain. Combined, the effect stacks and can overshoot the safe range.
Action: NEVER combine or rapidly switch without prescriber guidance. Talk to your GP or prescribing pharmacist. Wash-out periods of 1-2 weeks (longer for fluoxetine) are typically required between St John's Wort and prescribed serotonergics in either direction.
Source: BNF St John's Wort + NICE NG222
Transplant immunosuppressants (ciclosporin, tacrolimus, sirolimus, everolimus) · high
Effect: REDUCED PLASMA LEVELS — transplant rejection risk. Multiple cases of organ rejection in transplant recipients who started St John's Wort have been reported. Contraindicated.
Mechanism: St John's Wort induces CYP3A4 and P-glycoprotein; these are the principal routes by which immunosuppressants are metabolised and distributed.
Action: Do NOT start St John's Wort. If you are already on it, tell your transplant team immediately.
Source: MHRA Drug Safety Update + BNF St John's Wort
HIV antiretrovirals (protease inhibitors, NNRTIs) · high
Effect: REDUCED PLASMA LEVELS — HIV treatment failure and resistance development risk. Contraindicated during antiretroviral therapy.
Mechanism: CYP3A4 + P-glycoprotein induction reduces plasma levels of protease inhibitors (indinavir, ritonavir-boosted regimens) and NNRTIs (efavirenz, etravirine, nevirapine).
Action: Tell your HIV care team about any supplement use, especially St John's Wort. Do not start St John's Wort during antiretroviral therapy.
Source: BNF St John's Wort
Warfarin and DOACs (apixaban, rivaroxaban, edoxaban, dabigatran) · high
Effect: Anticoagulant effect REDUCED. INR can swing on starting AND on stopping St John's Wort. Bleeding or clotting risk depending on direction of change.
Mechanism: CYP2C9 induction reduces warfarin effect; CYP3A4 + P-gp induction reduces DOAC plasma levels.
Action: Tell your anticoagulation clinic about ANY St John's Wort use, including starting AND stopping. Do not adjust anticoagulant dose without prescriber guidance.
Source: BNF Warfarin sodium + BNF St John's Wort
Cancer treatments (imatinib, irinotecan, vinca alkaloids, taxanes, kinase inhibitors) · high
Effect: REDUCED PLASMA LEVELS — chemotherapy failure risk. Contraindicated during active cancer treatment.
Mechanism: CYP3A4 + P-glycoprotein induction reduces plasma levels of the many cancer treatments that depend on these pathways for metabolism / distribution.
Action: Tell your oncologist or specialist clinical pharmacist BEFORE starting any supplement during cancer treatment. Do not start St John's Wort during active chemotherapy.
Source: BNF St John's Wort + clinical oncology consensus
Digoxin — induced P-gp efflux reduces digoxin AUC; possible heart-failure decompensation or atrial-fibrillation rate-control loss. Tell your prescriber.
Linezolid (antibiotic with MAOI activity) — serotonin-syndrome risk on combination. Tell your prescriber.
Dextromethorphan (cough suppressant in many UK over-the-counter cold remedies) — serotonergic; serotonin-syndrome risk. Tell your pharmacist.
Antiepileptics — carbamazepine, phenytoin, perampanel, lamotrigine. CYP induction reduces anticonvulsant plasma levels; seizure-control loss risk. Tell your prescriber.
Statins — atorvastatin, simvastatin, lovastatin. CYP3A4 induction reduces statin effect. Tell your prescriber.
Calcium-channel blockers — amlodipine, diltiazem, verapamil, nifedipine. CYP3A4 induction reduces blood-pressure effect. Tell your prescriber.
Oral diabetes medicines — gliclazide, glimepiride (CYP2C9 substrates). Induction may reduce blood-sugar control. Tell your prescriber.
PPIs (omeprazole), theophylline, midazolam, alfentanil — CYP3A4 substrates with reduced plasma levels on St John's Wort. Tell your prescriber.
Antiarrhythmics — amiodarone (CYP3A4), digoxin (P-gp). Both routes may apply. Tell your prescriber.
SAM-e supplements — additive serotonergic load; serotonin-syndrome risk. Tell your pharmacist.
Tell your prescriber if you take any of these combinations. This is not personalised advice.
This is not an exhaustive list. Always tell your prescriber and pharmacist about every supplement you take.
Common side effects
- GI symptoms (nausea, abdominal pain, dry mouth).
- Headache.
- Restlessness or agitation.
- Sleep disturbance.
- Photosensitivity — burning, redness, or rash on sun-exposed skin, particularly in pale-skinned individuals at higher doses.
Rare side effects
- Mania or hypomania in individuals with bipolar disorder.
- Severe photosensitivity reactions including blistering.
- Withdrawal-like symptoms on abrupt discontinuation after prolonged use.
- Allergic reactions including rash, urticaria, and rare anaphylaxis.
How to take it
- Typical supplemental range
- UK MHRA Traditional Herbal Registration (THR) products are registered at hyperforin/hypericin strengths corresponding to approximately 600-1800 mg/day of standardised extract. Trial materials in mild-to-moderate depression literature span the same range (LI-160, WS 5570, ZE 117, STW3-VI). Lower-strength food-supplement St John's Wort is sold without a UK health claim and is not directly comparable to trial materials.
- Timing
- Daily — split doses (morning + evening) are typical in trial protocols. Effects on mood emerge over 2-4 weeks of regular use; drug-interaction effects develop over 10-14 days.
How to spot quality
Look for
- MHRA THR licence number on the pack ("THR XXXXX/XXXX") for traditional-use registered products. THR registration is the UK regulatory route that permits "slightly low mood / slight anxiety" wording.
- Standardisation declared by hyperforin and/or hypericin percentage — the bioactives most relevant to both effect and interaction profile.
- Branded extract identifier (LI-160, WS 5570, ZE 117, STW3-VI) for trial-matched material.
- Drug-interaction warning visible on the pack — the MHRA THR labelling rules require this for registered products.
- GMP-certified manufacture.
Red flags
- Marketing as a "natural antidepressant" or "natural Prozac" — the THR scope does not authorise this and clinical-equivalence framing to a Prescription-Only Medicine is not permitted.
- Marketing implying use for diagnosed moderate or severe depression — outside both the THR scope and UK NICE pathways.
- No drug-interaction warning on the pack.
- No hyperforin / hypericin standardisation declared.
- Naturalness-as-safety arguments — directly counter to the documented interaction profile.
- Marketing alongside 5-HTP, L-tryptophan, SAM-e, or other serotonergic supplements without an explicit "do not combine" warning — risks serotonin syndrome.
Commonly combined with
Other ingredients that share a biological pathway, cofactor relationship, or evidence-backed protocol with this one. Mechanisms below cite primary physiology — not folk pairing. Doses are literature ranges, not recommendations. Talk to your pharmacist or GP before changing your stack, especially if you take prescription medication.
Methyl Folate (5-Methyltetrahydrofolate)
Limited evidenceSometimes co-formulated in "natural mood" supplements because folate status modulates monoaminergic function. Mechanism plausibility is moderate; trial evidence on the combination is limited.
Folate (and its activated form L-5-MTHF) is a methyl-group donor in the synthesis of serotonin, dopamine, and noradrenaline via the BH4 (tetrahydrobiopterin) cofactor cycle. People with folate deficiency or with the MTHFR C677T polymorphism have lower CSF folate and altered monoamine metabolism, and folate supplementation has been studied as an adjunct to SSRI antidepressants.
St John's Wort acts on the same monoamine system through serotonin/noradrenaline/dopamine reuptake inhibition. Combining the two is mechanistically coherent — folate provides the substrate, St John's Wort modulates the reuptake.
Trial evidence specific to the combination is limited; the strongest folate-as-mood-adjunct trials (Papakostas 2012 L-methylfolate + SSRI in treatment-resistant depression) used SSRIs, not St John's Wort. The combination appears in commercial supplements but is not a UK-recognised pathway. Folate supplementation alone is not associated with St John's Wort's drug-interaction profile.
Evidence: Folate-as-mood-adjunct evidence is concentrated on SSRI co-prescription (Papakostas 2012, Am J Psychiatry). Direct combination trials with St John's Wort are not published. UK NICE NG222 does not include either in the depression pathway. [2]
Doses studied: 300-1800 mg/day standardised St John's Wort extract with 400-800 µg/day folate (or 400-1000 µg L-5-MTHF for MTHFR-variant individuals). Not a Camden recommendation — trial evidence is limited and the SJW drug-interaction profile is unchanged by the combination.
Vitamin B6
Limited evidenceB6 (pyridoxal-5-phosphate) is a cofactor for serotonin and dopamine synthesis. Sometimes co-formulated with St John's Wort in mood supplements; mechanism is supportive rather than synergistic.
Pyridoxal-5-phosphate (the active form of vitamin B6) is the cofactor for aromatic L-amino acid decarboxylase (AADC), which converts 5-HTP to serotonin and L-DOPA to dopamine. B6 status modulates monoamine biosynthesis capacity but does not amplify St John's Wort's reuptake-inhibition effect; the combination is supportive (substrate availability), not synergistic.
Standard NRV-tier B6 supplementation (1.4 mg/day adult NRV) is well below any therapeutic threshold. Higher-dose B6 (>10 mg/day chronically) carries its own peripheral neuropathy concern documented in the EFSA opinion. Camden's vitamin-b6 carries the upper-limit detail.
Evidence: B6 cofactor role for monoamine synthesis is well-established; direct trial evidence for B6 + St John's Wort combination on mood is absent. UK Article 13 authorised claim: "Vitamin B6 contributes to normal psychological function". [6]
Doses studied: 1.4-10 mg/day vitamin B6 (within NRV range) alongside standardised St John's Wort. Higher B6 doses are not advised because of peripheral neuropathy risk.
Vitamin B12
Limited evidenceB12 deficiency mimics depression — a screen-and-treat-deficiency-first principle. B12 is included in mood supplements alongside St John's Wort to cover the deficiency overlap.
Vitamin B12 deficiency (and folate deficiency, with which it shares the methylation pathway) can produce depressive symptoms, fatigue, and cognitive dulling indistinguishable from primary depression. UK GP practice on suspected depression includes a B12 / folate / ferritin screen specifically because deficiency is a treatable mimic.
B12 in a mood formulation is not synergistic with St John's Wort; it is a deficiency-cover mechanism — making sure that an underlying B12 deficiency is not the cause of the low mood the user is hoping the formulation will address. The two do not interact pharmacokinetically. UK Article 13 authorised claim: "Vitamin B12 contributes to normal psychological function".
Evidence: The B12-deficiency-mimics-depression literature is well-established (NHS GP guidance includes B12 in depression workup). Direct B12 + St John's Wort combination trials on mood are not published. [6]
Doses studied: 2.5-1000 µg/day vitamin B12 (UK NRV 2.5 µg; methylcobalamin or cyanocobalamin) alongside standardised St John's Wort. The B12 dose is for nutritional sufficiency, not pharmacological mood effect.
Ginkgo Biloba (leaf extract)
Limited evidenceDrug-interaction concern cluster — disclose both to any prescriber. St John's Wort is the canonical CYP / P-gp inducer reference.
Both have documented drug-interaction profiles. St John's Wort is the more-aggressive inducer. Camden st-johns-wort is the interaction reference.
Evidence: Camden st-johns-wort is the cluster reference.
Doses studied: Disclose any combination to prescribing GP / pharmacist.
Panax Ginseng (Panax ginseng C.A. Meyer)
Limited evidenceDrug-interaction concern cluster — both Panax ginseng and St John's Wort have CYP / monoaminergic interaction profiles requiring prescriber disclosure.
Both modulate CYP3A4 + monoaminergic signalling at different intensities. St John's Wort is the more-aggressive CYP / P-gp inducer; Panax ginseng has modest signals. Both should be disclosed to any prescriber. Camden st-johns-wort is the canonical interaction reference.
Evidence: Camden st-johns-wort is the cluster reference.
Doses studied: Disclose any combination to prescribing GP / pharmacist.
Verifera™ editorial perspective
Why it matters. St John's Wort is the encyclopaedia's defensive drug-interaction hub. More than a dozen other Verifera entries (5-HTP, L-tryptophan, ginseng, ginkgo, sage) reference this entry as the canonical example of a serotonergic CYP-inducing botanical. The editorial position is that this entry must be unambiguous about the "talk to your pharmacist first" rule and unambiguous about the MHRA Drug Safety Update history — and that the food-supplement- vs-THR distinction must be clear because UK consumers regularly encounter both shelf categories.
Where Camden lands. Camden Medicals does NOT stock St John's Wort in any form. UK NICE NG222 pathway for diagnosed depression is talking therapies and / or prescribed antidepressants; that is the NHS-grounded answer Camden would want a consumer to land on. This entry exists as a UK-anchored reference, including for consumers who arrive after seeing it on TikTok as a "natural Prozac" — the framing that prompted MHRA Drug Safety Updates.
If you want to explore further. For low mood or anxiety in the UK: the NHS pathway is to talk to your GP. NHS Talking Therapies (formerly IAPT) accepts self-referral in many areas — your local provider is searchable on NHS.uk. For research about the herbal medicine specifically: the BNF entry, NICE NG222, and the MHRA Drug Safety Update on St John's Wort are the canonical UK references. If you already take prescribed medication of any kind, do NOT start St John's Wort before talking to your pharmacist or GP — the interaction profile is the most-documented in herbal pharmacy.
How this entry was researched
Authoritative sources consulted:
- NHS depression and antidepressants pages
- NICE NG222 (Depression in adults) + CG113 (Generalised anxiety disorder) + CKS Depression
- BNF St John's Wort + warfarin entries
- MHRA Drug Safety Updates on St John's Wort (multiple, 2000-onwards)
- GB Nutrition and Health Claims (NHC) Register — no authorised claim for hypericum
- UK Traditional Herbal Registration (THR) scheme — MHRA herbal medicines register
- PubMed (via E-utilities MCP)
PubMed search terms:
Hypericum perforatum St John's Wort depression CochraneLinde Hypericum depression Cochrane meta-analysisSt John's Wort SSRI serotonin syndrome interaction
Literature search date: 2026-05-12
Sources listed are those consulted by the Verifera™ editorial team. Readers should verify against current authoritative sources.