Meta-analyses of quality clinical trials support a place for St. John's wort in the treatment of depression as mono- or adjunctive therapy. Effectiveness is comparable with standard antidepressants, while St. John's wort is associated with fewer and milder adverse reactions compared with conventional antidepressants. Benefit in reducing some climacteric symptoms in women with natural menopause has also been demonstrated. Unintended interactions with other drugs and quality control issues need to be considered prior to use. Limited data are available for several other areas of therapeutic use.
Preparations vary greatly in chemical content and quality, and may be standardized regarding quantity of hyperforin (commonly 3% to 5%) or hypericin (commonly 0.3%) constituents. Clinical trials evaluating the efficacy of St. John's wort in depression have commonly used 900 mg of extract daily in 3 divided doses for up to 12 weeks (range, 200 to 1,800 mg/day).
Use with various antineoplastics, anticoagulants, and anti-infectives (including antivirals), as well as boceprevir, cobicistat, telaprevir, and voriconazole is contraindicated.
Avoid use. Hypericin and hyperforin have been detected in breast milk. St. John's wort should be avoided during pregnancy and lactation until further long-term studies demonstrate a lack of toxicity in the developing fetus and breastfeeding infants.
St. John's wort has been reported to interact with numerous drugs. Drugs with a narrow therapeutic window should be monitored closely. Patients should be cautioned on the potential for interactions and consult their health care provider before taking St. John's wort with prescription or nonprescription drugs.
Adverse reactions are usually mild. Potential adverse reactions include GI symptoms (eg, dry mouth, dizziness, constipation) and confusion. Photosensitization may also occur. In clinical trials, adverse reactions and discontinuations due to adverse effects were usually less with St. John's wort than with standard antidepressants. Other possible rare adverse reactions include induction of mania and effects on male and female reproductive capabilities. Impaired glucose tolerance has been documented in healthy volunteers.
Information is lacking.
St. John's wort is a perennial plant native to Europe but found throughout the United States and parts of Canada. It is an aggressive weed that grows in the dry ground of roadsides, meadows, woods, and hedges. It generally reaches a height of 0.3 to 0.61 m, except on the Pacific coast where it has attained heights of 1.5 m.Awang 1991 The plant has oval-shaped leaves and yields golden-yellow flowers that bloom from June to September. The flower petals have black or yellow glandular dots and lines. There are approximately 370 species in the genus Hypericum, which is derived from the Greek words "hyper" and "eikon" meaning "over an apparition," alluding to the plant's ancient use to ward off evil spirits. "Perforatum" refers to the leaf's appearance; when held up to light, the translucent leaf glands resemble perforations.Hahn 1992, Upton 1997 Harvest of the plant for medicinal purposes occurs in July and August, and the plant material must be dried immediately to avoid loss of potency.Bombardelli 1995 The dried herb consists of the plant's flowering tops.Upton 1997
St. John's wort has been used as an herbal remedy for its anti-inflammatory and healing properties since the Middle Ages,Bombardelli 1995 with many herbalists, including Hippocrates and Pliny, recording its medicinal properties. It was noted for its wound-healing and diuretic properties, as well as for the treatment of neuralgic conditions such as back pain. In 1633, Gerard's Herbal recorded the plant's use as a balm for burns, and its oil was also popular during this time.Upton 1997 A reddish-colored olive oil extract made from the fresh flowers has been taken internally for the treatment of anxiety but has also been applied externally to relieve inflammation and promote healing.Hahn 1992
St. John's wort has been approved since 1984 by the German Commission E for the treatment of anxiety, depression, and insomnia. Although it fell into disuse for a time, a renewed interest, especially in Western countries, has led to use as a component of numerous preparations for treating anxiety and depression. The plant has been used in traditional medicine as an antidepressant and a diuretic, as well as for gastritis and insomnia.Hahn 1992, Ng 2017, Russo 2014 Topically, it was traditionally used in the management of wounds, bruises, skin ulcers, cuts, burns, contusions, myalgia, and hemorrhoids, and as an antiseptic.Samadi 2010, Yucel 2017 It is now licensed in many European countries and widely prescribed for depression.Ng 2017
Several reports regarding the chemical components in St. John's wort are available.Butterweck 2007, Mauri 2000, Schmitt 2006, Wurglics 2006 More than 150 constituents have been identified that interact in synergistic, additive, and antagonistic manners to produce a variety of actions. The most commonly described constituents are naphthodianthrones, flavonoids, phloroglucinols, and essential oils. The naphthodianthrones (hypericin, pseudohypericin) and the phloroglucinols (hyperforin, adhyperforin) are the most characterized.Russo 2014
Naphthodianthrons occur in St. John's wort in concentrations of less than 0.1% to 0.15%. The anthraquinone derivatives hypericin and pseudohypericin (also emodin-anthranol and cyclo-pseudohypericin) are the best known components of the plant. Isohypericin and protohypericin are also present. The reddish dianthrone pigment hypericin (Hypericum red) ranges from 0.02% to 2.5%, depending on harvesting period, drying process, and storage.Bombardelli 1995, Newall 1996 Hypericin content varies widely among growing regions, and concentrations are contingent on plant part, with flowers, buds, top leaves, and secondary stems yielding the highest percents.Upton 1997 Microscopic evaluation revealed that hypericin accumulates in secretory cell globules within these plant structures.Liu 1999 Numerous reports concerning high-performance liquid chromatography analysis of hypericin in St. John's wort exist.Balogh 1999, Chi 1999, Fourneron 1999, Michelitsch 2000, Mulinacci 1999, Sirvent 2000, Stochmal 1998, Tateo 1998 Liposoluble pigments from the plant, including hypericin, carotenoids, and chlorophylls, have also been reported.Omarova 1998 A review of the chemistry of phenanthroperylene quinones from hypericin reveals photosensory pigments.Falk 1999
Flavonoid concentrations in St. John's wort occur at less than 12% in flowers and approximately 7% in leaves/stalksUpton 1997 and include kaempferol, quercetin, quercitrin, isoquercitrin, amentoflavone, luteolin, myricetin, hyperin, hyperoside, rutin, miquelianin, and astilbin.Bombardelli 1995, Butterweck 2000, Newall 1996, Upton 1997 The proanthocyanidins (approximately 12% of aerial parts) are certain forms of catechin and epicatechin.Upton 1997
Other compounds present in St. John's wort include xanthones (1.28 mg per 100 g) and tannins (3% to 16%). One study reports that tannin content in extracts is influenced by parameters such as temperature of maceration.Rafajlovska 1998 Phenol constituents include caffeic, chlorogenic, and p-coumaric acids, and hyperfolin. Other plant constituents include acids (eg, nicotinic, myristic, palmitic, stearic), carotenoids, choline, pectin, hydrocarbons, and long-chain alcohols. Amino acids include cysteine, gamma-aminobutyric acid (GABA), glutamine, leucine, lysine, and others.Bombardelli 1995, Hahn 1992, Newall 1996, Upton 1997
St. John's wort products are not regulated by the US Food and Drug Administration because they are classified as dietary supplements.Congress 1994 Several reports evaluating commercial preparations of St. John's wort have found inconsistencies in active ingredients, such as potency variations of labeled hypericin concentrations (from 47% to 165%),Constantine 1998 different concentrations of major components among brands,Liu 1999 and marked deviations in hyperforin and adhyperforin amounts in certain preparations.Melzer 1998 Several reports address these issues, with various proposed standardization methods.Khwaja 1999, Kurth 1998, Mason 1999, Schempp 1999
Animal and human studies have elucidated the pharmacokinetic differences among the structurally similar components hypericin, pseudohypericin, and hyperforin. Bioavailability of these constituents after oral administration is low and ranges from approximately 15% to 20%. Penetration of the blood-brain barrier is similarly low with only about 5% of hypericin likely to reach the brain; hypericin's half-life in the brain appears to be a few weeks.(Russo 2014) Time to peak plasma levels (Cmax) ranges from 30 minutes to 3 hours for pseudohypericin, from 4.6 to 8.1 hours for hypericin, and about 2.8 to 3.6 hours for hyperforin after single doses of St. John's wort (range, 300 to 1,800 mg [approximately 0.3% of hypericins]).(Hammer 2014, Russo 2014) Steady-state levels of hypericin are reached at 4 days, with a prolonged plasma half-life of about 25 hours due to hypericin's high affinity for albumin and lipoprotein. Hyperforin exhibits linear pharmacokinetics at doses up to 600 mg, after which plasma levels tend to be lower than expected. After repeat doses of 900 mg/day of extract, hyperforin steady-state levels of about 100 ng/mL have been reported, with a half-life of 9 hours.(Russo 2014)
St. John's wort, particularly hyperforin, has been shown in vitro and in vivo to inhibit monoamine oxidase type A (MAO-A) and MAO-B as well as the reuptake of norepinephrine, dopamine, and serotonin. It has a strong affinity for GABA, glutamate, and adenosine receptors.(Sood 2010) It induces the cytochrome P450 (CYP-450) system, the uridine diphosphate glucuronosyltransferase (UGT) isozyme, and P-glycoprotein.(Kummer 2016, Markert 2015, Pereira 2013) Downregulation of beta-adrenergic receptors has also been documented.(Russo 2014) The major coactive constituents shown to mediate the broad-spectrum inhibition of neurotransmitter reuptake are hypericin, hyperforin, quercetin, and kaempferol.(Chrubasik-Hausmann 2018)
Bioactivities of the various constituents in St. John's wort are a result not only of their bioavailability but also of the complex interactions of the constituents themselves, some of which are light dependent. This complexity also highlights the challenge of interpreting existing data.(Hammer 2014)
In vitro studies revealed that St. John's wort at low concentrations is capable of increasing immunity, but at high concentrations can suppress immunity.(Cabrelle 2008, Evstifeeva 1996, Fidan 2008, Mukerjee 2008) A number of signaling pathways elicited by compounds in Hypericum have been identified in human and animal cell cultures and in vivo in animal models. Quercetin, amentoflavone, hyperforin, and hypericin have been shown to individually reduce nuclear factor kappa B, tumor necrosis factor alpha (TNF-alpha), cyclooxygenase-2, p38, and other key factors in inflammatory signaling pathways. Combining the individual compounds altered the resulting activities, reflecting apparent interactions among the constituents of St. John's wort when combined. Additionally, bioactivities of some compounds were dependent on light, whereas others were light independent. These interactions appear to provide a balance of both pro- and anti-inflammatory activities, as well as phototoxic and photoprotective actions. Pseudohypericin was a necessary element in the anti-inflammatory process, as it was required for the reduction in prostaglandin E2.(Hammer 2014) Similarly, St. John's wort ethanolic extract inhibited the increase in neutrophil recruitment and the inflammatory biomarkers interleukin 1beta (IL-1beta) and TNF-alpha as well as the decrease in glutathione that was induced by acetaminophen toxicity in mice. Subsequently, AST and ALT levels were also decreased. A dose-dependent reduction in acetaminophen-induced lethality was also observed.(Hohmann 2015)
Antiviral activity has been reported for influenza, herpes simplex types 1 and 2 (HSV-1, HSV-2), Sindbis virus, poliovirus, retrovirus infection in vitro and in vivo, murine cytomegalovirus, and hepatitis C.(Bombardelli 1995, Jacobson 2001, Müller 2004, Newall 1996, Upton 1997) Hypericin and pseudohypericin exert unique effective antiviral actions, possibly because of nonspecific associations with cellular and viral membranes. Hypericin and pseudohypericin inhibit a variety of encapsulated viruses, including HIV.(Upton 1997)
3-Hydroxy lauric acid obtained from H. perforatum exhibited light-independent, anti-HIV activity in an in vitro experiment.(Maury 2009)
Clinical trials of St. John's wort use in HIV are limited by the prevalence of interactions between St. John's wort and standard HIV therapy. In 1999, a phase 1 study evaluating hypericin's effects in 30 patients concluded that hypericin had no antiretroviral activity, with phototoxicity being observed.(Gulick 1999)
Antiviral activity may involve a photoactivation process, as exposure of hypericin to fluorescent light markedly increases antiviral activity.(Bombardelli 1995, Maury 2009) An example of this was demonstrated in a case series in which an approximate 50% improvement was observed in acyclovir-recalcitrant herpes skin lesions treated with a phototherapy protocol that included H. perforatum (10% extract containing 1% w/v hypericin and 0.5% w/v chlorophyll) as the photosensitizer compared to phototherapy with red laser therapy alone. Patients ranged in age from 7 to 77 years and presented with HSV-1, HSV-2, or combination-type lesions.(Tardivo 2012)
Platelet response improved significantly subsequent to administration of St. John's wort versus placebo in clopidogrel nonresponders with stable angina who underwent elective percutaneous coronary intervention (PCI). In a small, open-label, randomized clinical trial (N=23), known clopidogrel nonresponders were randomized 2:1 to receive St. John's wort 300 mg 3 times daily or placebo, in addition to dual antiplatelet therapy (aspirin 80 mg and clopidogrel 75 mg), for 2 weeks after PCI. Platelet response improved significantly when measured as P2Y12 reaction units to clopidogrel but not when measured as thrombin receptor activating peptide units to thrombin receptor activating peptide or as aspirin reaction units or arachidonic acid units to aspirin, which indicated a selective interaction of St. John's wort with the clopidogrel pathway.(Trana 2013)
There is no evidence of efficacy for St. John's wort in anxiety disorders in randomized controlled trials as a primary outcome, including generalized social anxiety disorder.(Kobak 2005b) Reduction in associated anxiety has been reported as a secondary outcome in 2 clinical trials of St. John's wort, one in patients with major depression, the other in patients with somatization disorder.(Mannel 2020, Volz 2003)
Meta-analyses, including Cochrane meta-analyses, of quality clinical trials have been conducted to examine effects of St. John's wort in comparison with placebo and antidepressant therapy for treatment of depression.(Kasper 2008, Linde 2000, Linde 2005, Linde 2015, Magni 2013, Rahimi 2009) In some studies of mild, moderate, and major(Linde 2000, Seifritz 2016) depression, St. John's wort was more effective than placebo and similarly effective as standard antidepressants.(Kasper 2008, Linde 2000, Linde 2005, Linde 2015, Rahimi 2009, Sarris 2007, Seifritz 2016, Thachil 2007) Adverse effects are lower for St. John's wort than for standard antidepressants.(Asher 2017, Knüppel 2004, Linde 2000, Qaseem 2016, Rahimi 2009, Thachil 2007) A previous Cochrane review found insufficient evidence to support a place in therapy for St. John's wort in treating major depression(Linde 2005); however, more recent trials and analysis of participants meeting criteria for major depression have led to a somewhat more positive, but cautious, recommendation for Hypericum.(Linde 2000, Qaseem 2016) Issues raised in the meta-analyses include the heterogeneity of older clinical trials, the wide variation and quality of Hypericum preparations, use of comparatively low doses of pharmaceutical antidepressants, and the emergence of more favorable trials.(Asher 2017, Linde 2000, Linde 2005, Qaseem 2016, Sarris 2007) Limited evidence is available for use in depression in adolescents(Charrois 2007, Sarris 2007, Walter 1999) or the elderly, or for patients with comorbid conditions such as Alzheimer disease(Chatterjee 1999) or anxiety.(Sarris 2009) However, one analysis of 4 studies (N=1,058) that used a stabilized dry extract of H. perforatum, WS 5570, showed a significant improvement in depression scores (P<0.01) compared to placebo in younger patients (younger than 60 years) as well as older patients (60 years of age and older).(Kasper 2015)
More recent meta-analyses examining the benefits and risks of St. John's wort compared to selective serotonin reuptake inhibitors (SSRIs), specifically in patients with major depressive disorder (MDD), found no statistically significant difference in response, remission, and depression scores between the 2 treatments. As in earlier studies, the risks of treatment were significantly higher for SSRIs than St. John's wort, as was treatment discontinuation due to adverse events.(Asher 2017, Magni 2013, Ng 2017, Purgato 2014) St. John's wort was also shown in head-to-head comparisons in network meta-analyses to have superior efficacy in MDD when compared to exercise and omega-3 fatty acids.(Asher 2017) Commercial extracts used were mostly standardized to hypericin 0.12% to 0.3% and hyperforin 2% to 5%; doses ranged from 300 to 1,800 mg/day given over 4 to 12 weeks. Two meta-analyses evaluating data on SSRIs as a group included 12 randomized controlled trials (RCTs) (N=1,806)(Asher 2017) and 27 RCTs (N=3,808), repsectively.(Ng 2017) Overall, the strength of evidence was considered low by one paper because of the moderate to low doses of comparator antidepressants used in the studies.(Asher 2017)
Further studies have shown St. John's wort to be effective in the acute treatment of mild depression at a range of dosages (600 to 1,200 mg daily),(Kasper 2008) while long-term studies describe clinical advantage over placebo with regard to time to relapse and overall relapse rates when St. John's wort 900 mg daily was administered over 26 and 52 weeks.(Brattström 2009, Kasper 2008) Unintended drug-herb interactions with St. John's wort may compromise the efficacy of other drugs; however, St John's wort as adjunctive therapy has been used clinically to reduce the dose needed for pharmaceutical antidepressants.(Izzo 2016, Ravindran 2016) Additionally, as in clinical trials with pharmaceutical antidepressants, a significant placebo effect and similar placebo response pattern occurs in MDD trials with St. John's wort, such that nonresponders will likely exhibit no clinical response early in the trial (ie, within the first 4 weeks) and placebo responders will experience a clinical response within the first 2 weeks of the trial.(Sarris 2013)
Guidelines discussing the use of St. John's wort in MDD have been published. The American Psychiatric Association practice guideline for the treatment of patients with MDD recognizes that while modest evidence supports the use of St. John's wort, data are conflicting and insufficient to make a recommendation for its use in the treatment of MDD. In addition, careful attention to drug-drug interactions is needed with St. John's wort. However, the guidelines also state that in patients who prefer complementary and alternative therapies, St. John's wort may be considered.(Gelenberg 2010) The Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of MDD in adults (2016) recommend St. John's wort as first-line monotherapy in mild to moderate MDD based on level 1 evidence (defined as at least 2 RCTs with adequate sample sizes, preferably placebo-controlled, and/or meta-analysis with narrow confidence interval). St. John's wort is recommended as second-line adjunctive therapy in moderate and higher-severity MDD, based on level 2 data (defined as at least 1 RCT with adequate sample size and/or meta-analysis with wide confidence intervals).(Ravindran 2016) The American College of Physicians clinical practice guideline for treatment of adults with MDD report no significant difference in response or remission (low-quality evidence) but better tolerability (moderate-quality evidence) with St. John's wort monotherapy compared to low-dose second-generation antidepressants. Due to the lack of rigorous standardization of product purity and potency in the United States, data were deemed insufficient to recommend a place in therapy for St. John's wort in the treatment of MDD.(Qaseem 2016) The Veteran’s Affairs and Department of Defense (VA/DoD) clinical practice guideline for the management of major depressive disorder (2022) recommends the use of standardized extract of St. John’s wort as monotherapy in patients with mild MDD who are not pregnant or breastfeeding and who prefer herbal treatments to first-line psychotherapy or pharmacotherapy (weak).(VA/DoD 2022)
Based on efficacy in depression, Hypericum extracts have been recommended as appropriate therapy in mild or moderate depression with bipolar disorder as an alternative to standard antidepressant therapy.(Andreescu 2008) A trial (N=54) evaluating the efficacy of 900 mg of Hypericum extract daily in adolescents with attention-deficit/hyperactivity disorder and a subsequent systematic review found no difference compared with placebo at 8 weeks(Sarris 2011, Weber 2008) and no difference using the same dosage in burning mouth syndrome.(Sardella 2008) St. John's wort 600 mg/day performed better than placebo in 6 primary outcome measures in patients with somatoform disorders.(Müller 2004) Equivocal results have been demonstrated for Hypericum extracts in the management of premenstrual symptoms, which may be reflective of the different dosages used.(Hicks 2004, Stevinson 2000) Improvement in total, behavioral, and physical symptoms in women diagnosed with premenstrual syndrome (PMS) has been demonstrated with Hypericum compared to placebo in double-blind RCTs that include a small crossover pilot study (N=36) and a larger prospective trial (N=170).(Canning 2010, Ghazanfarpour 2011)
Seasonal affective disorder, a type of depression in which symptoms occur in fall/winter and resolve in spring/summer, improved with St. John's wort in combination with light therapy.(Martinez 1994) In an open-label trial, statistically but not clinically significant improvements in several target behaviors in 3 young autistic males (19 to 22 years of age) were documented after 4 weeks of St. John's wort 20 mg/day. The patients were resistant to previous treatment with neuroleptics or methylphenidate.(Niederhofer 2009)
St. John's wort was identified as one of the 3 most common herbs used by certified or licensed midwives for postpartum depression based on state-wide surveys in California, Texas, and North Carolina.(Dennehy 2010)
The Scottish Intercollegiate Guidelines Network (SIGN) guidelines on the management of perinatal mood disorders (2012) state that St John's wort and other alternative medicines should not be used during pregnancy and lactation based on lack of evidence specific to use in perinatal mood disorders, the risk of drug interactions, and lack of regulation for such products.(SIGN 2012)
No significant effect was found with St John's wort compared to placebo in Yale-Brown Obsessive-Compulsive Scale total or subscale scores in patients with at least a 1-year history of primary obsessive-compulsive disorder (OCD). Patients received a flexible dose of St John's wort (minimum dose, 300 mg twice daily) or placebo for 12 weeks in a double-blind, randomized fashion. The most common adverse events reported with St John's wort were headache, GI symptoms, fatigue, agitation, and sleep disturbance.(Kobak 2005a)
A case of reduced hyperbilirubinemia, decreased fatigue, and improved quality of life has been reported in a patient with congenital Crigler-Najjar syndrome type II. The patient was administered 2 regimens given 18 months apart of Hypericum dry extract 300 mg 3 times daily for 8 weeks.(Kummer 2016)
Equivocal results have been reported by 2 studies using St. John's wort 900 mg/day in patients with irritable bowel syndrome (IBS).(Saito 2010, Wan 2010) In a small pilot study (N=30), 8 weeks of treatment with St. John's wort significantly improved psychological well-being, with improved scores on anxiety and depression scales (P<0.05). Autonomic response to physical stimuli was also significantly improved (P<0.01), but not to psychological stressors. Symptom improvement was reported for pain, bloating, and overall severity (P<0.05).(Wan 2010) However, in another study, placebo provided significantly better responses in overall symptom severity and diarrhea, and provided adequate relief in a 12-week double-blind RCT that enrolled 70 symptomatic adults with IBS.(Saito 2010)
A systematic review and meta-analysis assessing safety and efficacy of St. John's wort preparations in women who experienced natural menopause identified 9 studies (N=6,983) that met inclusion criteria, 6 of which were included in the efficacy meta-analysis (N=717). Interventions included H. perforatum as monotherapy (3 studies) as well as in combination with chaste tree or black cohosh. The meta-analysis revealed a significant improvement with St. John's wort in climacteric scale scores overall (standard mean difference, –1.08; 95% CI, –1.38 to –0.77; P<0.0001), with moderate heterogeneity, and in hot flush scores (standard mean difference, –0.64; 95% CI, –0.78 to –0.5; P<0.0001), with no heterogeneity. In addition to the overall improvement in hot flushes, hot flush severity, duration, and frequency also improved significantly (P<0.0001 each). However, no significant difference was found in depression scores. The 4 trials included in the safety analysis showed no difference between treatment and placebo.(Liu 2014) Similar results were reported with H. perforatum for hot flush frequency and intensity in a double-blind, randomized, placebo-controlled trial conducted in 80 postmenopausal women. However, in contrast, this study also reported a significant reduction in depression intensity for those taking hypericum. After the intervention, 80% vs 5.7% reported no depression in the treatment group vs control, respectively (P<0.001).(Eatemadnia 2019)
The updated American Association of Clinical Endocrinologists and American College of Endocrinology position statement on menopause (2017) advises against the use of St. John's wort for treatment of hot flushes in breast cancer survivors.(Cobin 2017) The Society of Obstetricians and Gynaecologists of Canada revised clinical practice guidelines on managing menopause (2014) recommend that complementary and alternative medicine that has demonstrated efficacy for mild menopausal symptoms, including St. John's wort for healthy mood balance and associated sleep disturbances, may be offered (level I-B evidence).(Reid 2014) Another Canadian organization, the Committee on the Evolution of Practices in Oncology (CEPO), recommends against the use of St. John's wort for managing hot flashes in breast cancer survivors (level II evidence [ie, evidence demonstrated by small randomized trials with uncertain results), as no benefit was shown over placebo; however, the single study reviewed did report significant improvements in sleep and quality-of-life measures in the St. John's wort group (900 mg/day for 3 months).(L'Espérance 2013)
St. John's wort was investigated in an open-label pilot study in 21 patients with restless legs syndrome. All 17 patients who reported at least a 70% improvement in symptom severity scores and improved sleep during the 10-day induction phase opted to enter the 3-month continuation phase. During phase 1, a St. John's wort 300 mg standardized extract was taken daily. However, during phase 2, a dose of 300 mg was recommended to be taken daily for 4 to 5 days, stopped until symptoms recurred, and then continued as needed for the duration of the study. After 3 months, median severity score had improved significantly from 24 (±5.1) at baseline to 4.1 (±1) (P<0.0001). The St. John's wort regimen was taken for a median of 40 days during the 3-month period, with symptom-free periods ranging from 2 to 7 days (median, 3 days). No adverse effects were reported.(Pereira 2013)
A double-blind, placebo-controlled trial conducted in 11 healthy volunteers demonstrated the ability of an H. perforatum extract cream (1.5%) rich in hyperforin to significantly improve protection of irradiated skin from radicals (80.6% reduction in radicals) compared to untreated skin; the placebo cream led to a 55.7% reduction in radical production.(Arndt 2013) Of the 8 trials included in a systematic review investigating topical herbal medicines for atopic eczema, one small double-blind, randomized, placebo-controlled trial published in 2003 assessed the safety and efficacy of a hyperforin topical cream in 21 patients (12 to 59 years of age). After 4 weeks, the topical H. perforatum cream significantly improved the intensity of eczema (ie, erythema, papulation, crust, excoriation, lichenification, scaling) as well as reduced S. aureus skin colonization compared to placebo. A few nonserious adverse events were reported. Risk of bias was low across all domains.(Thandar 2017) In a small pilot study (N=10), both St. John's wort and vehicle alone significantly improved erythema, scaling, and thickness in plaques of patients with mild psoriasis. Application of St. John's wort resulted in greater reduction in erythema scores, scaling scores, and thickness scores, with improvement in scaling being the most pronounced; on a 3-point scale, a mean difference of –1.8 and –0.3 was observed for treatment and vehicle, respectively. No between-group comparative statistics were provided.(Najafizadeh 2012)
The joint American Academy of Dermatology and National Psoriasis Foundation (AAD-NPF) guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures (2020) states that the use of topical St. John's wort may lower the severity of symptoms; however, the lack of standardized, commercially available products or robust clinical data prohibit recommendations for use.(Elmets 2020)
A limited number of animal studies exist evaluating the role of Hypericum extracts in reducing craving and symptoms of withdrawal from morphine, ethanol, and stimulant substances (eg, nicotine, caffeine, amphetamine). Decreased self-administration of ethanol and withdrawal syndrome have been demonstrated in rodents, as well as no increased ethanol intake after periods of deprivation.(De Vry 1999, Ebrahimie 2015, Uzbay 2008, Uzbay 2008)
A Cochrane review of antidepressants for smoking cessation also examined evidence for herbal products, including St. John's wort. The evidence for St. John's wort suggests that it is not significantly better than placebo for this indication (2 studies, N=261; relative risk [RR], 0.81; 95% CI, 0.26 to 2.53).(Hughes 2014) Clinical trials have produced equivocal results regarding a role in smoking cessation, with one small trial (N=24) without a control group showing efficacy in cessation rates with Hypericum at 12 weeks(Lawvere 2006) and others showing no difference from placebo.(Camfield 2013, Parsons 2009, Uzbay 2008) A larger randomized, blinded, placebo-controlled, dose-ranging study similarly found no difference in smoking cessation rates, mean cigarettes smoked per day, withdrawal symptoms, or tobacco cravings in the St. John's wort 900 mg/day or 1,800 mg/day groups compared to placebo. Of the 118 cigarette smokers enrolled in the 12-week study, 43% withdrew before study end and were smoking during their last study visit.(Sood 2010) Differences in study populations, dosing, and formulation of preparations make comparisons difficult. Further quality studies are needed with larger numbers of subjects.
Topical and internal use of St. John's wort has been reported to provide effective wound healing. It stimulates fibroblast motility, collagen production, and keratinocyte differentiation, as well as possesses antimicrobial and anti-inflammatory effects. Hyperforin, hypericin, and derivatives of these constituents have been effective in treating skin ulcers, abrasions, burns, scratches, decubitus, and surgical wounds.
In a case report, the oily extract of St. John's wort was used to facilitate healing of decubitus ulceration.(Yucel 2017) St. John's wort was also observed to provide significantly more benefit to wound healing and scar formation in women who underwent cesarean section compared to placebo and untreated controls (P<0.001).(Samadi 2010)
A Cochrane review exploring herbal treatments for neuropathic pain (diabetic and nondiabetic) identified 1 randomized, placebo-controlled, double-blind crossover trial (n=47) that used St. John's wort (2,700 mg/day for 5 weeks). No significant effect on total or individual pain scores was found between groups.(Boyd 2019)
Of 31 complementary and alternative medicine (CAM) remedies, St Johns wort was one of the least recommended remedies for dental issues (30%) by German dentists and maxillofacial surgeons according to a prospective, cross-sectional survey (N=250). As one might expect, perceived effectiveness was rated higher among CAM proponents than opponents.(Baatsch 2017)
Preparations vary greatly in chemical content and quality, and may be standardized regarding hyperforin (commonly 2% to 5%) or hypericin (commonly 0.12% to 0.3%) content.Asher 2017, Linde 2005, Ng 2017, Wurglics 2006 Doses used for a variety of indications in clinical studies most commonly ranged from 300 mg/day to 1,800 mg/day.
Clinical trials evaluating the efficacy of St. John's wort in depression have commonly used 900 mg of extract daily in 3 divided doses for periods of up to 12 weeks (range, 200 to 1,800 mg/day).Kasper 2008, Linde 2000, Papakostas 2007
The use of St. John's wort in perinatal depression has been considered; however, insufficient data exist to support its use.Freeman 2009 There is a lack of systematic evidence on the safety of Hypericum in pregnancy or lactation.Dugoua 2006, Freeman 2009 A small study of case-matched infants born to mothers consuming St. John's wort during pregnancy found an increase in colic, drowsiness, and lethargy.Dugoua 2006
In 2 separate studies, the rates of major postnatal malformations (eg, hypospadias, bilateral hip dislocation, heart septum defect, obstructed ureter) in children of women exposed to St. John's wort while pregnant were 5% and 8.1%. A total of 5 cases of malformation were reported in 75 exposed live births; comparatively, malformations expected in the general population range from 3% to 5%. The differences reported in the studies were not statistically significantly different compared to women taking prescription antidepressants (4%) or those who were otherwise healthy and/or not exposed (0%). However, the hypericum-exposed sample sizes were small (N=38 and N=37), and caution is warranted in interpreting these results.Kolding 2015, Russo 2014 Case reports exist of low levels of hypericin and hyperforin detected in breast milk, but not in the breastfeeding infants.Freeman 2009, Klier 2006
St. John's wort should be avoided during pregnancy and lactation until further long-term studies demonstrate a lack of toxicity in the developing fetus and breastfeeding newborn.Freeman 2009, Kalra 2005
SIGN guidelines on the management of perinatal mood disorders (2012) state that St John's wort and other alternative medicines should not be used during pregnancy and lactation based on a lack of evidence specific to use in pregnancy or lactation, the risk of drug interactions, and lack of regulation for such products.SIGN 2012
Support for use of St. John's wort in surgical wound healing has been demonstrated in women who underwent caesarean section.Izzo 2016
Drug interactions with St. John's wort are highly variable and often difficult to predict based solely on the St. John's wort dose because of the complex interactions among hypericum constituents in any particular product or doseform.(Chrubasik-Hausmann 2018, Hammer 2014, Mueller 2004) Additionally, single-dose compared to long-term administration (ie, at least 10 days) of St. John's wort in drug interaction studies has been shown to have opposite effects on the pharmacokinetics of coadministered substrate drugs.(Borrelli 2009)
St. John's wort enhances the expression of the CYP-450 system, apparently as a result of binding to the nuclear pregnane X receptor (PXR). Hyperforin appears to be the specific receptor ligand and it is hyperforin content, not hypericin, that seems to most consistently determine the extent of the drug interaction, with 1 mg/day suggested as the critical cut-off dose for clinically significant interactions.(Chrubasik-Hausmann 2018, Kummer 2016, Pereira 2013) UGT isozyme induction is also mediated by PXR, so drugs metabolized by UGT have the potential to be affected by St. John's wort. The expression of P-glycoprotein (P-gp) is also stimulated by St. John's wort. Induction of both the intestinal and hepatic CYP3A4 has been observed.(Arold 2005, Kummer 2016, Markert 2015, Pereira 2013) Studies with voriconazole indicate that St. John's wort may be a stronger inducer of CYP2C19 and CYP2C9 than CYP3A4. Clinical studies have also reported induction of CYP2E1. However, the Food and Drug Administration reportedly classifies St. John's wort as a strong inducer (80% or greater decrease in area under the curve [AUC]) of CYP3A4 and a weak inducer (20% to 50% decrease in AUC) of CYP2C9.(Berry-Bibee 2016, Li 2017, Markert 2015, Russo 2014) The extent of induction of CYP3A4 and P-gp appears to be comparable among ethnic groups (ie, African American, white, Chinese, Hispanic, Indian, Malay).(Russo 2014) Organic anion-transporting polypepetides (OATPs) do not appear to be affected.(Li 2017, Markert 2015)
Abemaciclib: CYP3A4 inducers (moderate) may decrease the serum concentration of abemaciclib. Avoid combination.(Verzenio August 2018)
Acalabrutinib: CYP3A4 inducers (moderate) may decrease the serum concentration of acalabrutinib. Monitor therapy.(Calquence November 2019)
Afatinib: P-gp/ABCB1 inducers may decrease the serum concentration of afatinib. Consider therapy modification.(Gilotrif January 2018, Wind 2014)
Alfentanil: CYP3A4 inducers (moderate) may decrease the serum concentration of alfentanil. Consider therapy modification.(Alfentanil October 2019, Kharasch 2012)
Aliskiren: P-gp/ABCB1 inducers may decrease the serum concentration of aliskiren. Monitor therapy.(Tapaninen 2010, Tekturna June 2020)
Ambrisentan: St. John's wort may decrease the serum concentration of ambrisentan. No action needed.(Markert 2015)
Amiodarone: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of amiodarone. CYP3A4 inducers (moderate) may decrease the serum concentration of amiodarone. No action needed.(Nexterone November 2016, Nolan 1990, Oude 2018, Zarembski 1999)
Antihepaciviral combination products: CYP3A4 inducers (moderate) may decrease the serum concentration of antihepaciviral combination products. Avoid combination.(Technivie December 2019, Viekira Pak December 2019)
Apremiliast: CYP3A4 inducers (moderate) may decrease the serum concentration of apremilast. Monitor therapy.(Liu 2014, Otezla April 2020)
Aprepitant: CYP3A4 inducers (moderate) may decrease the serum concentration of aprepitant. Monitor therapy.(Emend November 2019)
Artemether and lumafantrine: St. John's wort may decrease serum concentrations of the active metabolite(s) of artemether and lumafantrine. Specifically, dihydroartemisinin concentrations, the active metabolite of artemether, may be decreased. St John's wort may decrease the serum concentration of artemether and lumafantrine. Avoid combination.(Coartem August 2019, Francis 2020)
Asunaprevir: CYP3A4 inducers (moderate) may decrease the serum concentration of asunaprevir. Avoid combination.(Sunvepra March 2016)
Atazanavir: St. John's wort may decrease the serum concentration of atazanavir. Avoid combination.(Reyataz September 2020)
Atogepant: CYP3A4 inducers (moderate) may decrease the serum concentration of atogepant. Consider therapy modification.(Qulipta September 2021)
Avacopan: CYP3A4 inducers (moderate) may decrease the serum concentration of Avacopan. Avoid combination.(Tavneos October 2021)
Avanafil: CYP3A4 inducers (moderate) may decrease the serum concentration of avanafil. Avoid combination.(Stendra August 2018)
Avapritinib: CYP3A4 inducers (moderate) may decrease the serum concentration of avapritinib. Avoid combination.(Ayvakit January 2020)
Belumosudil: CYP3A4 inducers (moderate) may decrease the serum concentration of belumosudil. Monitor therapy.(Rezurock July 2021)
Benzhydrocodone: CYP3A4 inducers (moderate) may decrease the serum concentration of benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Monitor therapy.(Apadaz February 2018)
Berotralstat: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of berotralstat. Avoid combination.(Orladeyo December 2020)
Bosentan: St John's wort may decrease the serum concentration of bosentan. No action needed.(Markert 2014)
Bosutinib: St. John's wort may decrease the serum concentration of bosutinib. Avoid combination.(Bosulif September 2012)
Brentuximab vedotin: CYP3A4 inducers (moderate) may decrease the serum concentration of brentuximab vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. No action needed.(Adcentris October 2019, Han 2013)
Brexpiprazole: St. John's wort may decrease the serum concentration of brexpiprazole. Consider therapy modification.(Rexulti July 2015)
Brigatinib: St. John's wort may decrease the serum concentration of brigatinib. Avoid combination.(Alunbrig April 2017)
Bupropion: St John's wort may enhance the adverse/toxic effect of bupropion. St John's wort may decrease the serum concentration of bupropion. No action needed.(Detweiler 2002, Lei 2010, Milton 2007)
Cabozantinib: St. John's wort may decrease the serum concentration of cabozantinib. Avoid combination. Management recommendations differ between cabozantinib capsules used for the treatment of medullary thyroid cancer and cabozantinib tablets used for the treatment of renal cell carcinoma.(Cabometyx April 2016, Cometriq November 2012)
Cannabidiol: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of cannabidiol. CYP3A4 inducers (moderate) may decrease the serum concentration of cannabidiol. No action needed.(Epidiolex October 2020, Jiang 2011, Stott 2013)
Cannabis: CYP3A4 inducers (moderate) may decrease the serum concentration of cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be decreased. Monitor therapy.(Stott 2013, Watanabe 2007)
Capmatinib: CYP3A4 inducers (moderate) may decrease the serum concentration of capmatinib. Avoid combination.(Tabrecta May 2020)
Cariprazine: CYP3A4 inducers (moderate) may decrease the serum concentration of cariprazine. Avoid combination. This combination is contraindicated in some non-US labeling.(Vraylar May 2019, Vraylar September 2022)
Carisoprodol: St. John's wort may increase serum concentrations of the active metabolite(s) of carisoprodol. Specifically, meprobamate concentrations may be increased. St. John's wort may decrease the serum concentration of carisoprodol. Monitor therapy.(Soma February 2013)
Celiprolol: P-gp/ABCB1 inducers may decrease the serum concentration of celiprolol. Monitor therapy.(Lilja 2004, Selectol July 2017)
Ceritinib: CYP3A4 inducers (moderate) may decrease the serum concentration of Ceritinib. Monitor therapy.(Zykadia March 2019)
Cladribine: P-gp/ABCB1 inducers may decrease the serum concentration of cladribine. Monitor therapy. This interaction is likely only clinically significant with orally administered cladribine.(Mavenclad March 2019)
Clarithromycin: CYP3A4 inducers (moderate) may increase serum concentrations of the active metabolite(s) of clarithromycin. CYP3A4 inducers (moderate) may decrease the serum concentration of clarithromycin. Consider therapy modification.(Biaxin September 2019, Hafner 1998, Kakuda 2014, Sustiva October 2019, Wallace 1995)
Cobimetinib: CYP3A4 inducers (moderate) may decrease the serum concentration of cobimetinib. Avoid combination.(Cotellic November 2015)
Copanlisib: CYP3A4 inducers (moderate) may decrease the serum concentration of copanlisib. Monitor therapy.(Aliqopa February 2020)
Crizotinib: CYP3A4 inducers (moderate) may decrease the serum concentration of crizotinib. Monitor therapy.(Xalkori June 2019, Xu 2015)
Daclatasvir: St John's wort may decrease the serum concentration of daclatasvir. Avoid combination.(Daklinza October 2019)
Daridorexant: CYP3A4 inducers (moderate) may decrease the serum concentration of daridorexant. Avoid combination.(Gehin 2021, Quviviq January 2022)
Darolutamide: Inducers of CYP3A4 (moderate) and P-glycoprotein may decrease the serum concentration of darolutamide. Avoid combination.(Nubeqa July 2019)
Darunavir: St John's wort may decrease the serum concentration of darunavir. Avoid combination.(Prezista December 2020)
Dasatinib: St. John's wort may decrease the serum concentration of dasatinib. Avoid combination.(Sprycel December 2018)
Deflazacort: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of deflazacort. Avoid combination.(Emflaza February 2017)
Delamanid: CYP3A4 inducers (moderate) may decrease the serum concentration of delamanid. No action needed.(Mallikaarjun 2016, Sasahara 2015)
Delavirdine: St John's wort may decrease the serum concentration of delavirdine. Avoid combination.(Rescriptor August 2019)
Dexlansoprazole: St John's wort may decrease the serum concentration of dexlansoprazole. Avoid combination.(Dexilant June 2018)
Diazepam: CYP3A4 inducers (moderate) may decrease the serum concentration of diazepam. Monitor therapy.(Ochs 1981, Ohnhaus 1987)
Docetaxel: St. John's wort may increase clearance and decrease AUC. No action needed.(Goey 2014)
Doxorubicin (conventional): P-glycoprotein/ABCB1 inducers may decrease the serum concentration of doxorubicin (conventional). Avoid combination.(Adriamycin March 2018)
Dronedarone: St. John's wort may decrease the serum concentration of dronedarone. Avoid combination.(Multaq November 2020)
Duvelisib: CYP3A4 inducers (moderate) may decrease the serum concentration of duvelisib. Consider therapy modification.(Copiktra September 2021)
Dydrogesterone: CYP3A4 inducers (moderate) may decrease the serum concentration of dydrogesterone. Monitor therapy.(Duphaston July 2018)
Elbasvir and grazoprevir: St John's wort may decrease the serum concentration of elbasvir and grazoprevir. Avoid combination.(Zepatier December 2019)
Elexacaftor, tezacaftor, and ivacaftor: St John's wort may decrease the serum concentration of elexacaftor, tezacaftor, and ivacaftor. Specifically, the serum concentration of ivacaftor may be decreased. Avoid combination.(Dresser 2003, Piscitelli 2000, Sugimoto 2001, Trikafta October 2019, Wang 2001)
Eliglustat: CYP3A4 inducers (moderate) may decrease the serum concentration of eliglustat. Monitor therapy.(Cerdelga August 2018, Vu 2020)
Encorafenib: CYP3A4 inducers (moderate) may decrease the serum concentration of encorafenib. Avoid combination.(Braftovi June 2018)
Eplerenone: St John's wort may decrease the serum concentration of eplerenone. No action needed.(Inspra May 2018)
Eravacycline: CYP3A4 inducers (moderate) may decrease the serum concentration of eravacycline. No action needed.(Newman 2019, Xerava August 2018)
Erdafitinib: CYP3A4 inducers (moderate) may decrease the serum concentration of erdafitinib. Consider therapy modification.(April 2019)
Esomeprazole: St. John's wort may decrease the serum concentration of esomeprazole. Avoid combination.(Nexium August 2021, Wang 2004)
Etoposide and Etoposide phosphate: CYP3A4 inducers (moderate) may decrease the serum concentration of etoposide. Monitor therapy.(Jouinot 2018, Rodman 1994)
Exemestane: St. John's wort may decrease the serum concentration of exemestane. Consider therapy modification.(Aromasin May 2018, Schwartzberg 2017)
Felodipine: CYP3A4 inducers (moderate) may decrease the serum concentration of felodipine. Monitor therapy.(Felodipine December 2020, Zaccara 1993)
Fexinidazole: CYP3A4 inducers (moderate) may increase serum concentrations of the active metabolite(s) of fexinidazole. Avoid combination.(Fexinidazole July 2021)
Finerenone: CYP3A4 inducers (moderate) may decrease the serum concentration of finerenone. Avoid combination.(Kerendia July 2021)
Flibanserin: CYP3A4 inducers (moderate) may decrease the serum concentration of flibanserin. Avoid combination.(Addyi August 2015)
Filgotinib: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of filgotinib. No action needed.(Hsueh 2022, Jyseleca January 2022)
Fosamprenavir: St John's wort may decrease the serum concentration of fosamprenavir. Avoid combination.(Lexiva March 2019)
Fosaprepitant: CYP3A4 inducers (moderate) may decrease the serum concentration of fosaprepitant. Specifically, CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite aprepitant. Monitor therapy.(Emend November 2019)
Fosnetupitant: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of fosnetupitant. Monitor therapy.(Akynzeo October 2020, Calcagnile 2013)
Fostamatinib: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of fostamatinib. Monitor therapy.(Martin 2016, Tavalisse April 2018)
Fostemsavir: St. John's wort may decrease serum concentrations of the active metabolite(s) of fostemsavir. Avoid combination.(Rukobia July 2020)
Futibatinib: Inducers of CYP3A4 (moderate) and P-glycoprotein may decrease the serum concentration of futibatinib. Monitor therapy.(Lytgobi September 2022)
Ganaxolone: CYP3A4 inducers (moderate) may decrease the serum concentration of ganaxolone. Consider therapy modification.(Ztalmy March 2022)
Gemigliptin: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of gemigliptin. CYP3A4 inducers (moderate) may decrease the serum concentration of gemigliptin. Monitor therapy.(Noh 2012, Zemiglo June 2012)
Gilteritinib: Inducers of CYP3A4 (moderate) and P-glycoprotein may decrease the serum concentration of gilteritinib. Monitor therapy.(James 2020, Xospata May 2019)
Glasdegib: CYP3A4 inducers (moderate) may decrease the serum concentration of glasdegib. Consider therapy modification.(Daurismo March 2020, Shaik 2018)
Glecaprevir and pibrentasvir: St. John's wort may decrease the serum concentration of glecaprevir and pibrentasvir. Avoid combination.(Mavyret August 2017)
Gliclazide: St. John's wort may decrease the serum concentration of gliclazide. Monitor therapy.(Diamicron July 2016, Xu 2008)
Guanfacine: CYP3A4 Inducers (moderate) may decrease the serum concentration of guanfacine. Consider therapy modification. The management of this interaction depends on the formulation of guanfacine used (extended-release or immediate release).(Intuniv December 2019, Li 2018, Tenex July 2013)
HMG-CoA reductase inhibitors (statins): St John's wort may decrease serum concentrations of the active metabolite(s) of HMG-CoA reductase inhibitors (statins). Consider therapy modification.(Eggertsen 2007, Sugimoto 2001)
Hydrocodone: CYP3A4 inducers (moderate) may decrease the serum concentration of hydrocodone. Monitor therapy.(Zohydro ER August 2014)
Hydrocortisone (systemic): CYP3A4 inducers (moderate) may decrease the serum concentration of hydrocortisone (systemic). Monitor therapy.(Kyriazopoulou 1984, Solu-Cortef November 2019)
Ibrexafungerp: CYP3A4 inducers (moderate) may decrease the serum concentration of ibrexafungerp. Avoid combination.(Brexafemme June 2021)
Idelalisib: CYP3A4 inducers (moderate) may decrease the serum concentration of idelalisib. Monitor therapy.(Jin 2015, Zydelig October 2020)
Ifosfamide: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of ifosfamide. CYP3A4 inducers (moderate) may increase serum concentrations of the active metabolite(s) of ifosfamide. Monitor therapy.(Chang 1997, Ifex March 2012, Kerbusch 2001)
Infigratinib: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of infigratinib. CYP3A4 inducers (moderate) may decrease the serum concentration of Infigratinib. Avoid combination.(Truseltiq May 2021)
Irinotecan products: St John's wort may decrease serum concentrations of the active metabolite(s) of irinotecan products. Specifically, concentrations of SN-38 may be reduced. St John's wort may decrease the serum concentration of irinotecan products. Consider therapy modification.(Camptosar January 2020, Mathijssen 2002, Onivyde October 2015)
Isavuconazonium sulfate: St John's wort may decrease serum concentrations of the active metabolite(s) of isavuconazonium sulfate. Specifically, St John's wort may decrease isavuconazole serum concentrations. Avoid combination.(Cresemba December 2019, Townsend 2017)
Isradipine: CYP3A4 inducers (moderate) may decrease the serum concentration of Isradipine. Monitor therapy.(Isradipine October 2018)
Istradefylline: St John's Wort may decrease the serum concentration of istradefylline. Avoid combination.(Mukai 2018, Nourianz August 2019)
Ivabradine: St. John's wort may decrease the serum concentration of ivabradine. Avoid combination.(Corlanor May 2019, Portolés 2006)
Ivosidenib: CYP3A4 inducers (moderate) may decrease the serum concentration of ivosidenib. No action needed.(Prakash 2020, Tibsovo May 2019)
Ixazomib: St John's wort may decrease the serum concentration of ixazomib. Avoid combination.(Gupta 2018, Ninlaro March 2021)
Ketamine: CYP3A4 inducers (moderate) may decrease the serum concentration of ketamine.Monitor therapy. This interaction is likely more clinically significant when ketamine is administered orally than when ketamine is administered via routes that bypass the gastrointestinal tract (eg, intravenous, nasal).(Noopers 2011, Peltoniemi 2012, Peltoniemi 2012, Spravato March 2019)
Ketozonazole (systemic): CYP3A4 inducers (moderate) may decrease the serum concentration of ketoconazole (systemic). Monitor therapy.(Ketoconazole March 2018, Sriwiriyajan 2007)
Lansoprazole: St John's wort may decrease the serum concentration of lansoprazole. Avoid combination.(Prevacid November 2020)
Lapatinib: St. John's wort may decrease the serum concentration of lapatinib. Avoid combination.(Smith 2009, Tykerb August 2011)
Larotrectinib: St John's wort may decrease the serum concentration of larotrectinib. Consider therapy modification.(Vitrakvi November 2018)
Lefamulin: CYP3A4 inducers (moderate) may decrease the serum concentration of lefamulin and lefamulin (intravenous) and P-gp/ABCB1 inducers may decrease the serum concentration of lefamulin. Consider therapy modification. The clinical significance of the interaction with CYP3A4 inducers (moderate) and lefamulin may be greater when using oral lefamulin compared with IV lefamulin.(Xelenta August 2019)
Lemborexant: CYP3A4 inducers (moderate) may decrease the serum concentration of lemborexant. Avoid combination.(Dayvigo December 2019, Landry 2021)
Lercanidipine: CYP3A4 inducers (moderate) may decrease the serum concentration of lercanidipine. Monitor therapy.(Zan-Extra November 2019)
Letermovir: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of letermovir. Avoid combination.(Prevymis August 2019)
Levoketoconazole: CYP3A4 inducers (moderate) may decrease the serum concentration of levoketoconazole. Monitor therapy.(Recorlev January 2022, Sriwiriyajan 2007)
Lonafarnib: CYP3A4 inducers (moderate) may decrease the serum concentration of Lonafarnib. Avoid combination.(Zokinvy November 2020)
Lopinavir: St John's wort may decrease the serum concentration of lopinavir. Avoid combination.(Kaletra October 2020)
Lorlatinib: CYP3A4 inducers (moderate) may enhance the hepatotoxic effect of lorlatinib. CYP3A4 inducers (moderate) may decrease the serum concentration of Lorlatinib. Consider therapy modification.(Lorbrena February 2021)
Lumateperone: CYP3A4 inducers (moderate) may decrease the serum concentration of lumateperone. Avoid combination.(Caplyta December 2019)
Lurasidone: St. John's wort may decrease the serum concentration of lurasidone. Avoid combination.(Latuda January 2017)
Lurbinectedin: CYP3A4 inducers (moderate) may decrease the serum concentration of lurbinectedin. Avoid combination.(Zepzelca June 2020)
Macimorelin: St. John's wort may decrease the serum concentration of macimorelin. Avoid combination.(Macrelin December 2017)
Macitentan: CYP3A4 inducers (moderate) may decrease the serum concentration of macitentan. Monitor therapy.(Bruderer 2012, Opsumit April 2019)
Maribavir: St John's wort may decrease the serum concentration of maribavir. Avoid combination.(Livtencity November 2021)
Mavacamten: CYP3A4 inducers (moderate) may decrease the serum concentration of Mavacamten. Avoid combination.(Zamzyos April 2022)
Mefloquine: CYP3A4 inducers (moderate) may decrease the serum concentration of mefloquine. Monitor therapy.(Mefloquine August 2017, Ridtitid 2000)
Meperidine: CYP3A4 inducers (moderate) may decrease the serum concentration of meperidine. Monitor therapy.(Demerol April 2019, Ramirez 2004)
Metformin: St John's wort may decrease the renal clearance of metformin. Improved glucose response may occur that has been shown to result from an acute increase in insulin response, which is independent of the glucose-lowering action of metformin.(Stage 2015)
Methoxsalen (systemic): Photosensitizing agents may enhance the photosensitizing effect of methoxsalen (systemic). Monitor therapy.(Oxsoralen-Ultra March 2003, Uvadex March 2021)
Mirodenafil: CYP3A4 inducers (moderate) may decrease the serum concentration of mirodenafil. Monitor therapy.(Shin 2009)
Mitapivat: CYP3A4 inducers (moderate) may decrease the serum concentration of mitapivat. Consider therapy modification.(Pyrukynd February 2022)
Mobocertinib: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of mobocertinib. CYP3A4 inducers (moderate) may decrease the serum concentration of mobocertinib. Avoid combination.(Exkivity September 2021, Zhang 2021)
Nadolol: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of nadolol. No action needed.(Misak 2016, Misaka 2013)
Naldemedine: CYP3A4 inducers (moderate) may decrease the serum concentration of naldemedine. Monitor therapy.(Fukumura 2020, Symproic January 2018)
Naloxegol: St. John's wort may decrease the serum concentration of naloxegol. Avoid combination.(Movantik September 2014)
Nateglinide: CYP3A4 inducers (moderate) may decrease the serum concentration of nateglinide. No action needed.(Niemi 2003, Starlix March 2017)
Nelfinavir: CYP3A4 inducers (moderate) may decrease the serum concentration of nelfinavir. Monitor therapy.(Viracept September 2016)
Neratinib: CYP3A4 inducers (moderate) may decrease the serum concentration of neratinib. Avoid combination.(Nerlynx June 2021)
Netupitant: CYP3A4 inducers (moderate) may decrease the serum concentration of netupitant. Monitor therapy.(Akynzeo December 2020, Calcagnile 2013)
Nilotinib: CYP3A4 inducers (moderate) may decrease the serum concentration of nilotinib. Monitor therapy.(Tanaka 2011, Tasigna December 2020)
Nilvadipine: CYP3A4 inducers (moderate) may decrease the serum concentration of nilvadipine. Monitor therapy.(Saima 2002, Yasui-Furukori 2002)
Nintedanib: Inducers of CYP3A4 (Moderate) and P-gp may decrease the serum concentration of nintedanib. Avoid combination.(Ofev March 2020)
Nirmatrelvir and ritonavir: St John's wort may decrease the serum concentration of nirmatrelvir and ritonavir. Avoid combination.(Paxlovid August 2022)
Nisoldipine: CYP3A4 inducers (moderate) may decrease the serum concentration of nisoldipine. Avoid combination.(Michelucci 1996, Sular December 2016)
Olaparib: CYP3A4 inducers (moderate) may decrease the serum concentration of olaparib. Avoid combination.(Dirix 2016, Lynparza January 2018)
Oliceridine: CYP3A4 inducers (moderate) may decrease the serum concentration of oliceridine. Monitor therapy.(Olinvyk August 2020)
Olmutinib: CYP3A4 inducers (moderate) may decrease the serum concentration of olmutinib. Monitor therapy.(Olita May 2020)
Omeprazole: St. John's wort may decrease the serum concentration of omeprazole. Avoid combination.(Nexium August 2021, Wang 2004)
Oxycodone: St. John's wort may decrease the serum concentration of oxycodone. Monitor therapy.(Nieminen 2010)
Paclitaxel (conventional): CYP3A4 inducers (moderate) may decrease the serum concentration of paclitaxel (conventional). Monitor therapy.(Marzolini 2017, Paclitaxel May 2018, Rodon 2012)
Paclitaxel (protein bound): CYP3A4 inducers (,oderate) may decrease the serum concentration of paclitaxel (protein bound). Monitor therapy.(Abraxane August 2020, Marzolini 2017, Rodon 2012)
Pacritinib: CYP3A4 inducers (moderate) may decrease the serum concentration of pacritinib. Avoid combination.(Vonjo February 2022)
Pazopanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PAZOPanib. Monitor therapy.(Votrient July 2020)
Pemigatinib: CYP3A4 inducers (moderate) may decrease the serum concentration of pemigatinib. Avoid combination.(Ji 2021, Pemazyre February 2021)
Pexidartinib: St. John's wort may decrease the serum concentration of pexidartinib. Avoid combination.(Turalio August 2019, Zahir 2022)
Pimavanserin: CYP3A4 inducers (moderate) may decrease the serum concentration of pimavanserin. Avoid combination.(Nuplazid November 2020)
Pitolisant: CYP3A4 inducers (moderate) may decrease the serum concentration of pitolisant. No action needed.(Wakix October 2020)
Ponatinib: CYP3A4 inducers (moderate) may decrease the serum concentration of ponatinib. Monitor therapy.(Iclusig December 2020, Narasimhan 2015)
Pralsetinib: CYP3A4 inducers (moderate) may decrease the serum concentration of pralsetinib. Monitor therapy.(Gavreto September 2020)
Praziquantel: CYP3A4 inducers (moderate) may decrease the serum concentration of praziquantel. Consider therapy modification.(Biltricide January 2019, Mutiti 2021)
Pretomanid: CYP3A4 inducers (moderate) may decrease the serum concentration of pretomanid. Avoid combination.(Dooley 2014, Pretomanid August 2019)
Propafenone: CYP3A4 inducers (moderate) may decrease the serum concentration of propafenone. No action needed.(Castel 1990, Dilger 1999, Dilger 2000)
Radotinib: St. John's wort may decrease the serum concentration of radotinib. Consider therapy modification.(Supect 2014)
Ramelteon: CYP3A4 inducers (moderate) may decrease the serum concentration of ramelteon. No action needed.(Rozerem December 2018)
Ranolazine: CYP3A4 inducers (moderate) may decrease the serum concentration of ranolazine. Avoid combination.(Ranexa December 2013)
Regorafenib: St John's wort may increase serum concentrations of the active metabolite(s) of regorafenib. St John's wort may decrease the serum concentration of regorafenib. Avoid combination.(Stivarga June 2020)
Relugolix: Inducers of CYP3A4 (moderate) and P-glycoprotein may decrease the serum concentration of relugolix. Monitor therapy.(Orgovyx December 2020)
Relugolix, estradiol, and norethindrone: Inducers of CYP3A4 (moderate) and P-glycoprotein may decrease the serum concentration of relugolix, estradiol, and norethindrone. Monitor therapy.(Myfembree May 2021)
Ribociclib: St. John's wort may decrease the serum concentration of ribociclib. Avoid combination.(Kisqali July 2020, Samant 2020)
Rimegepant: CYP3A4 inducers (moderate) may decrease the serum concentration of rimegepant. Avoid combination.(Nurtec ODT February 2020)
Riociguat: CYP3A4 inducers (moderate) may decrease the serum concentration of riociguat. No action needed.(Adempas January 2018, Saleh 2016)
Ripretinib: CYP3A4 inducers (moderate) may decrease the serum concentration of ripretinib. Consider therapy modification.(Qinlock June 2021)
Rivaroxaban: St. John’s wort may decrease the serum concentration of rivaroxaban. Avoid combination.(Huppertz 2018, Xarelto March 2017)
Roflumilast (systemic): CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of roflumilast (systemic). CYP3A4 inducers (moderate) may decrease the serum concentration of roflumilast (systemic). Monitor therapy.(Daliresp June 2018, Daxas January 2018, Nassr 2009)
Rolapitant: CYP3A4 inducers (moderate) may decrease the serum concentration of rolapitant. Monitor therapy.(Varubi August 2020, Wang 2019)
Ruxolitinib (systemic): CYP3A4 inducers (moderate) may increase serum concentrations of the active metabolite(s) of ruxolitinib (systemic). CYP3A4 inducers (moderate) may decrease the serum concentration of ruxolitinib (systemic). No action needed.(Branco 2016, Jakafi January 2020, Shi 2012)
Samidorphan: CYP3A4 inducers (moderate) may decrease the serum concentration of samidorphan. Monitor therapy.(Lybalvi May 2021, Sun 2019, Sun 2021)
Saxagliptin: CYP3A4 inducers (moderate) may decrease the serum concentration of saxagliptin. No action needed.(Onglyza February 2017, Upreti 2011)
Selpercatinib: CYP3A4 inducers (moderate) may decrease the serum concentration of selpercatinib. Avoid combination.(Retevmo May 2020)
Selumetinib: CYP3A4 inducers (moderate) may decrease the serum concentration of selumetinib. Avoid combination.(Dymond 2017, Koselugo April 2020)
Simeprevir: CYP3A4 inducers (moderate) may decrease the serum concentration of simeprevir. Avoid combination.(Olysio November 2017)
Siponimod: CYP3A4 inducers (moderate) may decrease the serum concentration of siponimod. Avoid use of CYP3A4 inducers (moderate) and siponimod in patients with the CYP2C9*1/*3 or CYP2C9*2/*3 genotypes. No action needed. The combination of siponimod and strong CYP3A4 inducers should not be used in patients who are CYP2C9 intermediate or poor metabolizers.(Gardin 2018, Huth 2019, Mayzent January 2021)
Sonidegib: CYP3A4 inducers (moderate) may decrease the serum concentration of sonidegib. Avoid combination.(Odomzo July 2015)
Sorafenib: St. John's wort may decrease the serum concentration of sorafenib. Monitor therapy.(Harding 2020, Nexavar July 2020)
Sotorasib: CYP3A4 inducers (moderate) may decrease the serum concentration of sotorasib. Monitor therapy.(Lumakras May 2021)
Sunitinib: St. John's wort may decrease the serum concentration of sunitinib. Avoid combination.(Sutent May 2011)
Suvorexant: CYP3A4 inducers (moderate) may decrease the serum concentration of suvorexant. Monitor therapy.(Belsomra March 2021, Wrishko 2019)
Tacrolimus (systemic): St. John's wort may decrease the serum concentration of tacrolimus (systemic). Consider therapy modification.(Herbert 2004, Mai 2003)
Tamoxifen: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of tamoxifen. CYP3A4 inducers (moderate) may decrease the serum concentration of tamoxifen. Monitor therapy.(Binkhorst 2012, Kivisto 1998, Soltamox April 2019, Targretin July 2015)
Tasimelteon: CYP3A4 inducers (moderate) may decrease the serum concentration of Tasimelteon. Monitor therapy.(Hetlioz December 2020, Ogilvie 2015)
Tazemetostat: CYP3A4 inducers (moderate) may decrease the serum concentration of tazemetostat. Avoid combination.(Tazverik January 2020)
Telithromycin: CYP3A4 inducers (moderate) may decrease the serum concentration of telithromycin. Monitor therapy.(Ketek December 2015)
Temsirolimus: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of temsirolimus. Specifically, sirolimus concentrations may be decreased. CYP3A4 inducers (moderate) may decrease the serum concentration of temsirolimus. Monitor therapy.(Boni 2007, Coriat 2011, Torisel March 2018)
Teniposide: CYP3A4 inducers (moderate) may decrease the serum concentration of teniposide. No action needed.(Baker 1992, Relling 2000)
Tetrahydrocannabinol: CYP3A4 inducers (moderate) may decrease the serum concentration of tetrahydrocannabinol. Monitor therapy.(Stott 2013, Watanabe 2007)
Tetrahydrocannabinol and cannabidiol: St John's wort may decrease the serum concentration of tetrahydrocannabinol and cannabidiol. Consider therapy modification.(Sativex December 2019, Stott 2013)
Thiopental: St. John's wort may enhance the CNS depressant effect of thiopental. Monitor therapy.(Thiopental January 2014)
Thiotepa: CYP3A4 inducers (moderate) may increase serum concentrations of the active metabolite(s) of thiotepa. CYP3A4 inducers (moderate) may decrease the serum concentration of thiotepa. Monitor therapy.(de Jonge 2005, Ekhart 2009, Tepadina January 2017)
Tiagabine: CYP3A4 inducers (moderate) may decrease the serum concentration of tiagabine. No action needed.(Gabitril August 2016, So 1995)
Ticagrelor: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of ticagrelor. CYP3A4 inducers (moderate) may decrease the serum concentration of ticagrelor. Monitor therapy.(Brilinta May 2020, Teng 2013, Weeks 2014)
Tipranavir: St. John's wort may decrease the serum concentration of tipranavir. Avoid combination.(Aptivus June 2020)
Tivozanib: CYP3A4 inducers (moderate) may decrease the serum concentration of tivozanib. Monitor therapy.(Cotreau 2015, Fotivda March 2021)
Tofacitinib: CYP3A4 inducers (moderate) may decrease the serum concentration of tofacitinib. Monitor therapy.(Nam 2020, Xeljanz December 2019)
Toremifene: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolite(s) of toremifene. CYP3A4 inducers (moderate) may decrease the serum concentration of toremifene. Monitor therapy.(Fareston May 2017, Kivisto 1998)
Trabectedin: St. John's wort may decrease the serum concentration of trabectedin. Avoid combination.(Machiels 2014, Yondelis July 2014)
Trazodone: CYP3A4 inducers (moderate) may decrease the serum concentration of trazodone. Monitor therapy.(Otani 1996, Trazodone October 2020)
Triazolam: CYP3A4 inducers (moderate) may decrease the serum concentration of triazolam. Monitor therapy.(Robertson 2002)
Ubrogepant: St John's wort may decrease the serum concentration of ubrogepant. Avoid combination.(Ubrelvy December 2019)
Ulipristal: CYP3A4 inducers (moderate) may decrease the serum concentration of ulipristal. Avoid combination.(Ella May 2018)
Upadacitinib: CYP3A4 inducers (moderate) may decrease the serum concentration of upadacitinib. Monitor therapy.(Mohamed 2017, Rinvoq August 2019)
Valbenazine: St. John's wort may decrease the serum concentration of valbenazine. Avoid combination.(Ingrezza April 2017)
Vandetanib: St. John's wort may decrease the serum concentration of vandetanib. Avoid combination.(Caprelsa June 2020, Martin 2011)
Vemurafenib: CYP3A4 inducers (moderate) may decrease the serum concentration of vemurafenib. Monitor therapy.(Zelboraf May 2020, Zhang 2019)
Venetoclax: CYP3A4 inducers (moderate) may decrease the serum concentration of venetoclax. Avoid combination.(Venclexta April 2016)
Vilazodone: CYP3A4 inducers (moderate) may decrease the serum concentration of vilazodone. Monitor therapy.(Boinpally 2014, Viibryd January 2020)
Vincristine (liposomal): P-glycoprotein/ABCB1 inducers may decrease the serum concentration of vincristine (liposomal). Avoid combination.(Marqibo June 2020, Villikka 1999)
Vinflunine: St. John's wort may decrease the serum concentration of vinflunine. Avoid combination.(Javlor September 2014, Zhao 2007)
Vitamin K antagonists: St. John's wort may increase the metabolism of vitamin K antagonists. Consider therapy modification.(De Smet 2000, Jiang 2004, Yue 2000)
Voclosporin: CYP3A4 inducers (moderate) may decrease the serum concentration of voclosporin. Avoid combination.(Ling 2014, Lupkynis January 2021)
Voriconazole: St. John's wort may decrease the serum concentration of voriconazole. Avoid combination.(Rengelshausen 2005, Vfend April 2021)
Vortioxetine: CYP3A4 inducers (moderate) may decrease the serum concentration of vortioxetine. Monitor therapy.(Brintellix September 2013, Chen 2013)
Voxelotor: CYP3A4 inducers (moderate) may decrease the serum concentration of voxelotor. Consider therapy modification.(Oxbryta December 2021)
Voxilaprevir: CYP3A4 inducers (moderate) may decrease the serum concentration of voxilaprevir. Avoid combination.(Vosevi September 2019)
Zaleplon: CYP3A4 inducers (moderate) may decrease the serum concentration of zaleplon. Monitor therapy.(Sonata August 2019)
Zanubrutinib: CYP3A4 inducers (moderate) may decrease the serum concentration of zanubrutinib. Avoid combination.(Brukinsa November 2019, Mu 2020, Wang 2021)
Zopiclone: CYP3A4 inducers (moderate) may decrease the serum concentration of zopiclone. Monitor therapy.(Villikka 1997, Zopiclone April 2020)
St John's wort interacts significantly with digoxin, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, amiodarone, and warfarin; avoid use in patients with heart failure.(Page 2016)
Some studies have reported insignificant pharmacokinetic drug interactions with natural products. Limited information, a lack of consistent use of standardized product formulations, as well as potentially high interpatient variability in clinical response warrants cautious interpretation and/or application of these data in practice.(Arold 2005)
A systematic review of current evidence concluded that Hypericum extracts are well tolerated and safe, aside from the potential for unintended interactions with other drugs.Clauson 2008,, Knüppel 2004, Schulz 2006, Stevinson 1999 A number of studies report no serious adverse effects, and in a review of clinical trials, St. John's wort was associated with fewer and milder adverse reactions compared with conventional antidepressants.Stevinson 1999 Adverse effects from H. perforatum were rare and mild. The most frequently described adverse reactions in clinical trials were GI complaints (eg, dry mouth, nausea, change in bowel habits), itching, rash, photosensitization, fatigue, dizziness, confusion, jitteriness, restlessness, insomnia, sedation, sleep disorders, and headache, most of which are attributed to hypericin and pseudohypericin content.Knüppel 2004, Qaseem 2016, Russo 2014, Schulz 2006, Stevinson 1999 Induction of mania has been associated with St. John's wort.Moses 2000, Nierenberg 1999 The volatile oil of St. John's wort is an irritant.Newall 1996 A case report also associated use of St. John's wort with hyponatremia that resulted from syndrome of inappropriate secretion of antidiuretic hormone (SIADH), which has been reported with all classes of synthetic antidepressants.Jones 2014 The contribution of St. John's wort consumption could not be ruled out in a case of development of an extremely rare form of hepatocellular carcinoma in a patient with chronic alcoholism.Lampri 2014
One case report describes acute neuropathy after sun exposure in a patient using St. John's wort.Bove 1998 When ingested, hypericin can induce photosensitization characterized by inflammation of the skin and mucous membranes (including human keratinocytes and lens epithelial cells) following exposure to light, which generates reactive oxidative species that damage axonal membranes directly and activates a calcium-ion channel (transient receptor potential cation channel A1, TRPA1) expressed on peripheral sensory neurons. Pseudohypericin and hyperforin also act as photoirritants.Araya 1981, Beattie 2005, Bernd 1999, He 2004, Hohmann 2016, Kümper 1989, Schempp 1999 However, most reports of photosensitivity have been limited to patients taking excessive doses of H. perforatum, primarily to treat HIV.Murray 1997 For example, both IV (eg, 0.5 mg/kg twice weekly) and oral dosing (eg, 0.5 mg/kg/day) of H. perforatum caused phototoxicity in 30 patients with HIV, with 16 of 30 discontinuing treatment for this reason.Jacobson 2001 Adverse phototoxic neurological effects have also been shown to have a gender-specific association. Specifically 5 of 6 females, but 0 of 6 males, developed dermatologic and neurologic symptoms on sun-exposed areas of the back of the hands and perioral and nasal areas within 6 days of increasing the dose of St. John's wort from 300 mg to 600 mg (3 times daily). Gender specificity for neuropathic effects has also been noted in the German Federal Institute for Drugs and Medical Devices. Gender differences in the dermal expression of interleukins may be involved in this differential response.Hohmann 2016 An interaction of constituents, as found in the whole plant, has been shown to reduce the toxicity of hypericum extracts.Hammer 2014
Long-term treatment (up to 21 days) with St. John's wort significantly increased 2-hour plasma glucose levels (by approximately 40%), total glucose AUC (by 18%), and incremental blood glucose AUC (by 48%) in 10 healthy men. This effect was not only sustained but increased at 6 weeks following the last dose (240 to 294 mg of dry extract and 900 mcg total hypericin twice daily). Six weeks after the last dose, total glucose AUC increased by an additional 17% and incrementally by an additional 31%. Insulin disposition indices suggest that St. John's wort reduces glucose-stimulated insulin secretion during the oral glucose tolerance test.Stage 2016
Limited information on genotoxicity exists. Potent inhibition of sperm motility was observed in vitro.Ondrizek 1999
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
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