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SCIENTIFIC NAME:
Hypericum perforatum
FAMILY NAME:
Clusiaceae/Hypericaceae/Guttiferae
COMMON NAME:
St. John's Wort
  Evidence for Efficacy (Human Data)
   Clinical Trials  (176)
   Observational Studies/Case Reports  (96)
   Traditional and Folk Use  (65)
  Safety Data
   Adverse Effects & Toxicity  (70)
   Interactions  (115)
   Contraindications  (12)
  Evidence of Activity
   Animal Studies  (96)
   Pharmacodynamics  (307)
   Analytical Chemistry  (141)
   Pharmacokinetics (ADME)  (41)
   Genetics & Molecular Biology  (27)
  Formulas/Blends
   Modern Methods of Preparation  (33)
   Patents  (25)
   Folk Blends (component)  (0)
   Contemporary Mixtures (component)  (0)
  Other Information
   Pictures & Distribution Maps  (6)
   Cultivation, Conservation & Ecology  (24)
   Related Links  (6)
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  History of Records
   History of Record (1)
 
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EVIDENCE FOR EFFICACY (HUMAN DATA)
 
Clinical Trials
  A preliminary clinical study 28 smokers of 10 or more cigarettes per day for at least one year has not provided convincing evidence that a St John's wort herb extract plus individual motivational/behavioural support is likely to be effective as an aid in smoking cessation. Barnes 2006
  A systematic review of randomized controlled trials on St. John's Wort (SJW) and the treatment of mild to moderate depression demonstrated a drop in the Hamilton Depression Rating Scale scores for clients taking SJW compared with placebo or pharmaceutical antidepressants. Clement 2006
  In women using oral contraceptive pills (OCPs) and St. John's wort (SJW) simultaneously, it appears that SJW does not interfere with the antiandrogenic properties of OCPs. Fogle 2006
  Hypericum perforatum may enhance salivary cortisol via a U-shaped dose-response relationship in 20 healthy male volunteers which may be mediated through a 5-HT2 mechanism. Franklin 2006
  The quality of reporting of randomized controlled trials of herbal medicine interventions including echinacea, ginkgo, St. John's wort, and kava have been reviewed. Gagnier 2006
  A double-blind, randomised, placebo-controlled, multicentre clinical study reveals that St John's wort is a good alternative to chemically defined antidepressants in the treatment of 388 outpatients with moderate depression. Gastpar 2006
  Hypericum perforatum extract WS 5570 at doses of 600 mg once daily and 600 mg twice daily were found to be safe in 332 patients and more effective than placebo, with comparable efficacy of the WS 5570 groups for the treatment of mild to moderate major depression. Kasper 2006
  Standardized St. John's Wort as 450 mg capsules twice daily in 37 smokers, exhibited feasibility for use in smoking cessation. Lawvere 2006
  In the analyses of 72 outpatients with mild to moderate depression, patients receiving Hypericum perforatum had the lowest remission rates compared to fluoxetine (34.6%) and placebo (45%). Moreno 2006
  It was found in a study conducted on 42 male, healthy volunteers who were administered St. John's wort & hyperforin that the extent of induction of CYP3A varies with St. John's wort products and also depends on hyperforin dose. Mueller 2006
  Hypericum extract LI160 has demonstrated a ketamine-antagonising effect and it is examined whether LI160 reverses changes of a low dose ketamine on auditory evoked potentials in healthy subjects. Murck 2006
  Only in a secondary analysis, pooling of both lower (0.12%) or a higher (0.18%) hypericine formulation treated groups showed that Hypericum has a clinical significant effect in minor depressed patients with HAM-D up to 17 and the finding was significant only in non-dysthymic patients. Randlov 2006
  The effect of two different hypericum extracts (STW 3, STW 3-VI) on photosensitivity with respect to minimal erythema dose (MED) after 14 days treatment was investigated by open, multiple-dose & one-phase studies which were conducted in 20 healthy men, receiving one tablet/day. Schulz 2006
  Of the 100 participants with eating disorder symptoms 64% used an herbal product including Dexatrim and St. John's Wort for weight loss and they had the highest reported use. Steffen 2006
  Enough data are available on three herbs (ginkgo (Ginkgo biloba), St John's wort (Hypericum perforatum) and saw palmetto (Serenoa repens)) for meta-analyses of single-herb interventions. Walker 2006
  [St. John's wort reduces effectiveness of anticancer medication.] [No authors listed] 2005
  The pharmacokinetic interaction between a low-hyperforin St John's wort extract and alprazolam, caffeine, tolbutamide, and digoxin was evaluated in 28 healthy volunteers. Arold 2005
  Comparision of efficacy of Hypericum LI 160 (H LI 160) to fluoxetine & placebo in a 4-week randomized, double-blind trial with 163 patients revealed that H LI 160 or fluoxetine were not more effective in short-term treatment in mild to moderate depression than placebo. Bjerkenstedt 2005
  Recent clinical studies, have reported potential therapeutic effects for hypericum in the treatment of smoking cessation, for prickly pear extract in the prevention of alcohol hangover and magnesium supplementation as an adjunct to methadone treatment. Dean 2005
  [St John's wort is at least as effective as paroxetine in reducing severity of depression and is better tolerated.] Ernst 2005
  The presence of early improvement on the 17-item Hamilton Rating Scale for Depression concerning fatigue and general somatic symptoms is significantly predictive of achieving remission at endpoint with hypericum treatment but not with placebo. Farabaugh 2005
  Comparision of antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo & fluoxetine in patients with major depressive disorder revealed that St John's wort was significantly more effective than fluoxetine & showed a trend toward superiority over placebo. Fava 2005
  Review on the effectiveness(EFNS) of treatments for depression in older people reveals that there is limited evidence to support the EFNS of transcranial magnetic stimulation, dialectical behaviour therapy, interpersonal therapy,light therapy, St John's wort & folate in reducing depressive symptoms. Frazer 2005
  Hypericum extract STW 3 at a dose of 612 mg once daily for up to 24 weeks in 123 patients with moderate depression is not inferior to sertraline and it is a well-tolerated drug for the treatment of moderate depression. Gastpar 2005
  A substantial fraction of the 594 patients treated with Hypericum extracts WS(R) 5570/5572 showed a meaningful reduction of depressive symptoms during the first two weeks of treatment, which was found to be a sensitive predictor of sustained response. Kieser 2005
  A double-blind study of St John's wort versus placebo in obsessive-compulsive disorder (OCD) with 60 subjects fail to support the efficacy of St John's wort for OCD. Kobak 2005
  The results from a placebo-controlled pilot study with 40 subjects failed to provide evidence for the efficacy of St. John's wort in social phobia. Kobak 2005a
  St. John's wort has been found to be superior to placebo and equivalent to standard antidepressants for the treatment of mild to moderate depression. Lawvere 2005
  Performance of a systematic review and meta-analysis of 37 double-blind randomised controlled trials reveals that Hypericum has minimal beneficial effects while other trials suggest that Hypericum and standard antidepressants have similar beneficial effects. Linde 2005a
  Update of 1998 Cochrane evidence-based review of SJW for depression found that the tested extracts seem more effective than placebo and similarly effective as standard antidepressants for treating mild to moderate depressive symptoms. Beneficial effects for treating major depression appear minimal. Linde 2005b
  An exploratory subgroup analysis of a three-armed study to compare Hypericum extract, fluoxetine, and placebo in 135 patients with major depressive disorder in a 12 week trial was performed. Murck 2005
  Coadministration of St. John's wort leads to a short-term but clinically irrelevant increase followed by a prolonged extensive reduction in voriconazole exposure in 16 healthy men stratified for CYP2C19 genotype. Rengelshausen 2005
  St John's wort is well tolerated in 26 patients and may be clinically effective in the treatment of some adolescents with mild depression. Simeon 2005
  In the treatment of moderate to severe major depression in 251 adult outpatients, hypericum extract WS 5570 was at least as effective as paroxetine and was better tolerated. Szegedi 2005
  Lack of herbal supplement characterization in published randomized controlled trials evaluating single-herb preparations of echinacea, garlic, ginkgo, saw palmetto, or St. John's wort has been reviewed. Wolsko 2005
  [CYP3A and P-glycoprotein activity induction with St. John's Wort in healthy volunteers from 6 ethnic populations.] Xie 2005
  The clinical effect of administering sufficient Hypericum perforatum to cattle to deliver quadruple the reported oral toxic dose was investigated which revealed that the reported bovine oral toxic dose of narrow leaved flowering stage biotype, H. perforatum was 3 g dried plant/kg body weight. Bourke 2004
  A review on several integrative treatments for depression, including omega-3 fatty acids, Hypericum perforatum (St. John's Wort), S-adenosyl-methionine, folate, 5-Hydroxytryptophan, acupuncture, exercise, & light therapy, with emphasis on issues pertinent to women has been evaluated. Freeman 2004
  During antidepressant treatment with 17 subjects, mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly (p <.0001), with no significant difference between St. John's wort nonresponders and placebo nonresponders. Gelenberg 2004
  The efficacy of St. John's wort (SJW) extract as a treatment for premenstrual symptoms was investigated as a randomized, double-blinded, placebo-controlled trial, with two parallel treatment groups which showed that there was a trend for SJW to be superior to placebo.. Hicks 2004
  In a placebo-controlled, double blind study, using 33 healthy volunteers it was found that Hypericin and pseudohypericin pharmacokinetics were only marginally influenced by comedication with the enzyme inhibitors and inducers cimetidine and carbamazepine. Johne 2004
  A study on150 patients aged > or = 18 yearsrevealed that unrecognized use of St John's wort is frequent and may have an important influence on the effectiveness and safety of drug therapy during hospital stay. Martin-Facklam 2004
  Investigation of St. John's wort (SJW) on pharmacokinetics of theophylline in 12 healthy Japanese male volunteers showed that SJW caused no changes in pharmacokinetics of theophylline in plasma and SJW administration tended to increase ratio of 1U/the total amount excreted in urine. Morimoto 2004
  Administration of 600 mg of St. John's wort extract LI 160 daily in 184 outpatients was found to be effective and safe in the treatment of somatoform disorders. Muller 2004
  A randomised double-blind crossover study was performed with 19 healthy subjects to examine the effects of Hypericum extract (LI160) on intravenously administered cortisol on auditory evoked potentials (AEPs) and salivary cortisol concentration. Murck 2004
  Compared to synthetic antidepressants St. John's Wort demonstrated similar effectiveness and in the sub-group of mild to moderate depression, the herbal antidepressant showed better results against the synthetic antidepressants. [Article in German] Roder 2004
  A post-marketing surveillance was conducted to investigate if the single-dose-administration of highlydosed St. John's Wort extract improves quality of life. [Article in German] Rudolf 2004
  In a double-blind, randomized, placebo-controlled, crossover study, with 16 healthy subjects, it is found that St John's wort had no effect on blood pressure, heart rate, heart rate variability, or blood pressure variability. Schroeder 2004
  The effects of acute oral administration of high-dose Hypericum perforatum extract WS 5570 on the cortisol (COR), adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL) secretions were examined in 12 healthy male volunteers. Schule 2004
  The randomized, double-blind, placebo-controlled study showed that St. John's wort extract had no effect on vasoconstrictory response of cutaneous blood flow and skin conductance response in healthy volunteers. Siepmann 2004
  Hypericum extract STW 3-VI in a once-daily dosing regimen may be an effective and well-tolerated option for 140 outpatients with moderate depressive disorders. Uebelhack 2004
  Clinical trial with 12 healthy adult men indicates that St. John's wort was an inducer to the human CYP2C19. Wang 2004a
  Meta-analysis to reevaluate the effectiveness of St. John's wort as an antidepressant, funnel plot analysis, and meta-regression to assess the impact of publication bias, small-study effects, and variation in trial characteristics were performed. Werneke 2004
  Survey of prevalence and patterns of use of psychoactive medicines among individuals with autism in the Autism Society of Ohio in 747 families reveals that a total of 45.6% were taking some form of psychotropic agent (including St. John's wort and melatonin). Aman 2003
  Administration of St. John's wort extract to renal transplant patients receiving cyclosporin A (CSA) treatment resulted in a rapid and significant reduction of plasma CSA concentrations. Bauer 2003
  A survey of herbal use in children with attention-deficit-hyperactivity disorder or depression shows that herbal medicines were given most frequently for a behavioral condition, with ginkgo biloba, echinacea, and St. John's wort most prevalent. Cala 2003
  Primary care patients experiencing common menopausal symptoms are likely to use 4 herbal products including St. John's wort, Ginkgo biloba, and ginseng that are purported to provide menopause symptom relief, and many believe that these products improve their menopausal symptoms. Dailey 2003
  The effects of 12 days' pretreatment with St John's wort on the disposition of selected in vivo probe drugs were determined in 21 young healthy subjects. Dresser 2003
  An open-label pilot study of St. John's wort in juvenile depression indicate that St. John's wort may be an effective treatment for youths diagnosed with major depressive disorder. Findling 2003
  A prospective, observational, cohort study was conducted to examine the safety of St. John's wort to 33 nursing mothers and their infants, provided a framework for the management of breastfeeding women receiving St. John's wort. Lee 2003
  In the evaluation of drug therapy knowledge in liver transplant patients after pharmacy counseling, two women were identified as regularly using St John's Wort and were informed that this herbal medicine can endanger the success of organ transplantation. [Article in French] Monnier 2003
  It is proved that the symptoms associated with anxiety that severely afflict patients can be clearly improved more quickly with a combination therapy of St John's wort extract and valerian extract than with St John's wort monotherapy. Muller 2003
  A randomized controlled trial on interaction of St John's wort with low-dose oral contraceptive(LDOC) therapy in 18 healthy females showed that there was no evidence of ovulation during LDOC and St John's wort extract combination therapy, but intracyclic bleeding episodes increased. Pfrunder 2003
  The efficacy of a cream containing Hypericum extract standardised to 1.5% hyperforin in comparison to the corresponding vehicle (placebo) for the treatment of subacute Atopic Dermatitis was assessed in 21 patients. Schempp 2003
  The effect of Hypericum extract LI 160 on skin sensitivity to ultraviolet B (UVB), ultraviolet A (UVA), visible light (VIS) and solar simulated radiation was investigated in 72 volunteers of skin types II and III. Schempp 2003a
  Hypericum cream was found to be significantly superior to its vehicle in the topical treatment of mild to moderate atopic dermatitis in 21 patients. [Article in German] Schempp 2003a
  Hypericum preparation found to be therapeutically equivalent to fluoxetine and is therefore a rational alternative to synthetic antidepressants. Behnke 2002
  [Efficacy of continuation treatment with hypericum perforatum in depression.] Brenner 2002
  [St John's wort was not better than placebo for reducing depression scores.] Hawley 2002
  St John's wort increased expression and enhanced the drug efflux function of the multi drug transporter P-glycoprotein in peripheral blood lymphocytes of healthy volunteers. Hennessy 2002
  Study failed to support efficacy of H. perforatum for major depression. Hypericum Depression Trial Study Group
  St. John's wort extract may induce cytochrome P-450 enzymes or drug transporters (P-glycoprotein). Johne 2002
  The results of meta-analysis indicate that Hypericum extract accelerated the recovery from depression in a rather general manner, by influencing all investigated signs and symptoms of the disease in 544 out-patients suffering from mild to moderate depression. Kasper 2002
  Individuals harboring the *0/*0 genotype of glutathione-S-transferases mu 1 and theta 1 showed enhanced UVB-induced cutaneous damage after administration of Hypericum extract and GST genotypes modulated Hypericum-induced photosensitization. Kerb 2002
  H. perforatum extract was found to be safe and more effective than placebo for the treatment of mild to moderate depression. Lecrubier 2002
  It is reported that in a double-blind, placebo-controlled, randomized study the subjects receiving a combination of Citrus aurantium, caffeine and St John's Wort, lost significant amounts of total body weight while on a strict diet and exercise. Preuss 2002
  Review finds doses of 500-1000 mg of extract per day of preparations of St. John's Wort are of comparable efficiency to synthetic antidepressants in their normally prescribed dosages. Schulz 2002
  [St John's wort for the treatment of depression.] Shelton 2002
  Multiple doses of St John's wort extract do not affect heart rate variability nor cognitive function. Siepmann 2002
  Significantly more side effects were reported with the sertraline than with H. perforatum but no important differences in changes in mean Ham-D and BDI scores (using intention-to-treat analysis), with and without adjustment for baseline demographic characteristic. van Gurp 2002
  A multicentre, randomised, 6-week trial was carried out to compare efficacy of St John's wort extract (LI 160) (600 mg/day) & placebo in 151 out-patients suffering from somatization disorder (ICD-10: F45.0), undifferentiated somatoform disorder (F45.1), or somatoform autonomic dysfunctions (F45.3). Volz 2002
  A single dose of St John's wort resulted in significant inhibition of intestinal P-glycoprotein. Long-term treatment with St John's wort reversed changes in fexofenadine disposition observed with single-dose administration. Wang 2002
  [St. John's wort extract found not helpful for hepatitis C.] [No authors listed] 2001
  Hypericum, an antidepressant and antiviral medicine, was reported in 23 randomized clinical trials and found to be significantly more effective than placebo and had a similar level of effectiveness as standard antidepressants. [Article in Hebrew] Boniel 2001
  Hypericum does not have an acute nootropic effect in healthy humans at doses of 900 mg and 1800 mg but showed some impairing effect on accuracy of numeric working memory and delayed picture recognition at the higher dose. Ellis 2001
  H. perforatum extract may effect plasma hormonal changes via both 5-HT and DA-mediated mechanisms but do not involve noradrenaline, and hyperforin may be more important than hypericin for effecting these changes. Franklin 2001
  St. John's wort extract is equivalent to fluoxetine in treating depression and anxiety symptoms, with better safety and tolerability data. Friede 2001
  Hypericum is a potentially safe and effective treatment for children with symptoms of depression with good tolerability and no adverse events displayed. Hubner 2001
  Hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection. Jacobson 2001
  Kalb 2001
  A review showing that Safety and tolerability studies have revealed that St. John's wort preparations have better safety and tolerability profiles than synthetic antidepressants. Kasper 2001
  Evaluation of tissue regenerating action of a mixture of oily extracts of Hypericum perforatum and Calendula arvensis on surgical wounds from childbirth with caesarean section. Lavagna 2001
  The examination of effectiveness & tolerability of an extract of herba hyperici WS 5572 in multi-centre study with 2,166 patients, suffering from mild to moderate depression, shows its effectiveness & tolerability in patients suffering from mild & moderate depressive episodes. [Article in German] Rychlik 2001
  Otikon Otic Solution, a naturopathic herbal extract containing Allium sativum, Verbascum thapsus, Calendula flores, and H. perforatum in olive oil, is as effective as Anaesthetic ear drops and shown to be appropriate for the management of AOM-associated ear pain. Sarrell 2001
  Hypericum extract is able to influence central neurotransmitters, thereby causing COR stimulation in a dose-dependent manner. Schule 2001
  St John's wort was safe and well tolerated but not effective for treatment of major depression. Shelton 2001
  St. John's wort has no significant effect on pain in polyneuropathy. Sindrup 2001
  Hypericum had neutral effects on performance of psychological tests but showed a dose-related impairment on digit symbol substitution test. Timoshanko 2001
  Long-term SJW administration resulted in significant and selective induction of CYP3A activity of intestinal wall, but did not alter the CYP2C9, CYP1A2, or CYP2D6 activities. Wang 2001
  Meta-analysis showed St John's wort to be significantly more effective than placebo but not significantly different in efficacy from active antidepressants. Whiskey 2001
  "Antidepressive therapy. Hypericum extract Ll 160 highly effective " (German, no abstract) anon 2000
  50% reduction in depression scores (HAM-D & CGI) in 47% of the hypericum group (900 mg/d LI 160) and 40% of the sertraline/Zoloft group (75 mg/d) in a 7 week study with 28 mild to moderate depressed patients Brenner 2000
  Treatment with SJW for 14 days did not further induce the clearance of carbamazepine. Burstein 2000
  Early detection of bladder cancer by red hypericin fluorescence using 40 ml. of a 8 muM. solution which lasted 16 hours and gave 93% sensitivity and 98.5% specificity for detecting carcinoma in 40 patients D'Hallewin 2000
  The most recommended herb by both medical doctors & naturopaths was echinacea, followed by St John's Wort; in a survey of 242 practitioners Einarson 2000
  Exponential mixed-effects model of curve fitting for the results of antidepressant trials with an example from a placebo-controlled study with St. John's Wort Friede 2000
  Review found response rate of depression treated with St John's Wort was 23-55% higher than placebo, but 6-18% lower than tricyclic antidepressants. Rates of side effects were low, only 2.4% of 3250 patients, most commonly nausea (0.6%) Gaster 2000
  "Study provides additional support for hypericum extract " (news, no abstract) Miller 2000
  "Current pharmacologic therapy of depression " (German review, no abstract) Moller 2000
  Treatment with SJW for 14 days resulted in significant increases in the urinary 6-beta-hydroxycortisol/cortisol ratio suggesting that it induces CYP3A4. Roby 2000
  Topical application of St John's wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells. Schempp 2000
  While results do not provide evidence for a severe phototoxic potential of Hypericum oil and Hypericum ointment, detectable by the clinically relevant visual erythema score, there may be cause for concern in people with fair or diseased skin. Schempp 2000
  HAM-D decreased from 16-24 to 11.5 on Hypericum (Ze 117) or 12.2 on fluoxetine (SSRI) in a 6 week, double-blind trial with 240 patients. Hypericum safety was substantially superior with adverse events being only 8% vs. 23% Schrader 2000
  Modern antidepressants are no better than Hypericum of plant origin; meaning that safety, tolerability & acceptability of a medicine must be given much greater weight than its pharmacodynamics of simply testing against a placebo Schulz 2000
  PMS symptoms (diary and psychological tests) of depression, anxiety, etc were reduced in a study with 19 women taking 300 mg/d St John's Wort for 2 months Stevinson 2000
  H. perforatum showed 51% improvement in overall premenstrual syndrome scores with over two-thirds of the sample demonstrating at least a 50% decrease in symptom severity. Stevinson 2000
  Significant improvement of obsessive-compulsive disorder with a drop in Yale-Brown Obsessive Compulsive Scale score and most common side effects being diarrhea and restless sleep. Taylor 2000
  22% of presurgical patients reported the use of herbal remedies; especially echinacea, gingko biloba, St. John's wort, garlic & ginseng Tsen 2000
  Mean HAM-D reduction of all St. John's wort studies was 10.2 (52.9%), and for fluoxetine was 12.5 points (55.5%) in a review of controlled trials Volz 2000
  St John's wort may be a useful alternative to benzodiazepines to avoid nontreatment of early depression. Better tolerability than tricyclic antidepressants suggests benefit for elderly people. A review Vorbach 2000
  Evaluation of 315 clinical trials shows Hypericum was more effective than placebo for mild to moderate depression (risk ratio 1.9) but publication bias might inflate the benefit Williams 2000
  H. perforatum extract is therapeutically equivalent to imipramine in treating mild to moderate depression, but patients tolerate hypericum better. Woelk 2000
  Review finds safety and effectiveness with Hypericum for depression, Kava for anxiety and Valerian, catnip, chamomile, gotu kola, hops, lavender, passionflower, skullcap for sleep Cauffield 1999
  Evidence of herbs for the elderly includes Hypericum for depression, Ginkgo to delay dementia, Aesculus for venous insufficiency, Serenoa for BPH, Yohimbe for erectile dysfunction but still equivocal about Valerian for insomnia Ernst 1999
  "Is the antidepressant effect of Hypericum extracts depending on their hyperforin content? " (no abstract) Firenzuoli 1999
  Menopause psychological & psychosomatic symptoms diminished in 76% of participants by 900 mg/d Hypericum for 12 weeks in a trial with 111 women aged 43-65 Grube 1999
  HAMILTON global score fell from 16.6 to 7.9 with 800 mg of St. John's wort or from 17.2 to 8.11 with 20 mg fluoxetine in a study with 149 outpatients Harrer 1999
  800 mg/d St. John's wort (LoHyp-57) was equivalent to 20 mg/d fluoxetine (CAS 54910-89-3) in a 6 week trial with 149 elderly patients with mild or moderate depression, with HAMD decreasing from 14 to 6 and 15 to 7, respectively Harrer 1999
  von Zerssen depression score improved in 75% from 19.8-21.2 to 8.1-9.3 at week 6 for 647 mild to moderate depression patients taking hypericum extract LI 160 (Jarsin 300), 1 tablet t.i.d. Adverse events in 17% were mainly gastrointestinal (10%) Holsboer-Trachsler 1999
  Review of clinical trials indicates Hypericum is as effective as other antidepressants and more effective than placebo and side effects are less than current U.S.-approved antidepressants Josey 1999
  Review of 20 studies with 1,787 patients finds 600-900 mg is the effective dose and side effects are substantially fewer than with synthetic antidepressants. Photosensitization lacks clinical relevance at normal dosage Kasper 1999
  Meta-analysis utilizing only well-defined clinical trials found Hypericum was 1.5 times more likely to get an antidepressant response than placebo and was as effective as tricyclic antidepressants with only half the side effects Kim 1999
  "Hypericum special extract. Effectiveness in the elderly and in chronic disease " (German, no abstract) Lemmer 1999
  Hamilton depression score was reduced to half in 2/3 of 348 mild to moderate depression patients taking hypericin @ 0.17, 0.33 or 1 mg/d for 6 weeks. Mild adverse reaction were seen in 7 (2%) Lenoir 1999
  Inhibiting reuptake of all 3 major monoamines - 5-HT, noradrenaline & dopamine makes Hypericum the only antidepressant affecting all 3 with similar potencies. Better long-term studies are needed Nathan 1999
  "New discoveries on St John's wort can improve pharmacotherapy in depression " (Swedish, no abstract) Nordfors 1999
  Hamilton depression scores declined more with Hypericum extract (1050 mg/d) than imipramine (100 mg/d). Comparable results for Hamilton anxiety & clinical global impressions scales; in 8 week trial with 263 moderately depressed patients Philipp 1999
  "Special dialogue: Herbal remedies for depression " (no abstract) Stanga 1999
  More clinical studies since the Linde meta analysis (1996) provide further evidence that hypericum is superior to placebo in treating mild or moderate depression but comparison with modern antidepressants is insufficient Stevinson 1999
  Limitations on available clinical trials should temper our enthusiasm and argue for more research before accepting Hypericum extracts into our pharmacopoeia; a critical review and proposal for further research Vitiello 1999
  Seasonal affective disorder benefited after 8 weeks treatment with Hypericum (Kira) alone with a decline from 21.3 to 13 (n=168) or Hypericum plus light with a decline from 20.6 to 11.8 (n=133) Wheatley 1999
  SJW is a safe antidepressant with an apparently unique mode of action . It demonstrated efficacy in mild and moderate depression when compared with placebo or tricyclic antidepressants and needs to be compared with serotonin reuptake inhibitors Cott 1998
  High placebo response in Hypericum trials suggests mild transient depressions in participants so extrapolation to more serious or chronic depressions is unwarranted Deltito 1998
  Depression is one of the most common reasons for using complementary and alternative therapies but, except for exercise, Hypericum & acupuncture, the amount of rigorous scientific data to support the efficacy is extremely limited Ernst 1998
  Growing interest has led to a large randomized multicenter clinical trial of St. John's wort sponsored by NIMH Eskinazi 1998
  Review of therapeutic efficacy, mechanisms of actions, dosages and regimens, preparations, and adverse effects for melatonin, St John's wort, valerian, and kava-kava Heiligenstein 1998
  Review indicates 60-70% effectiveness for depression. It is well tolerated and adverse reactions are rare & mild (gastrointestinal, dizziness). If 900 mg/d does not help in 4-6 weeks other treatments should be tried Hippius 1998
  Hyperforin decreased Hamilton scale by 10.3 (45 mg/d), 8.5 (4.5 mg/d), 7.9 (placebo) in a 6 week, randomized, double-blind, trial with 147 outpatients suffering from mild or moderate depression Laakmann 1998
  Review indicates benefit for depression, seasonal affective disorder and in vitro antiviral activity. Traditionally used for wound healing, anti-inflammatory and analgesic activity Miller 1998
  Review finds 14 trials with Hypericum showing it is more effective than placebo for mild to moderate depression (risk ratio 1.9) but insufficient data comparing with standard antidepressants Mulrow 1998
  900 or 1800 mg, in a placebo controlled trial with healthy people, increased the latency to rapid eye movement (REM) sleep without producing any other effect on sleep, which is consistent with antidepressant activity Sharpley 1998
  Review indicates good evidence for the efficacy of St John's wort for depression and for ginkgo in the treatment of memory impairment caused by dementia Wong 1998
  "St. John's wort study launched " (no abstract) anon 1997
  After six-weeks treatment, increase in ECG first degree AV-blocks and abnormalities of repolarization for imipramine but a significant reduction for Hypericum in double blind study with 209 depression patients taking up to 1800 mg Czekalla 1997
  900 mg of hypericum for 4 weeks had reduced Hamilton Depression Rating Scale for seasonal affective disorder (SAD) patients. No added benefit was seen when bright light therapy was combined Kasper 1997
  Review of 25 controlled clinical trials shows improvement in 61% of patients on low-dose treatment (<1.2 mg hypericum extract) & 75% on a higher dose (2.7 mg). Side effects were mild and occurred at lower frequency than with other antidepressants Nordfors 1997
  Review of 12 placebo controlled trials with hypericum extracts shows mostly positive results Volz 1997
  6-week trial comparing 1800 mg extract LI 160 to 150 mg imipramine in severely depressed patients found similar reduction in the Hamilton Depression Scale Vorbach 1997
  6-week trial comparing 900 mg extract LI 160 to 75 mg amitriptyline in moderately depressed patients found similar reduction in the Hamilton Depression Scale. Adverse events with LI 160 in 37% vs. 64% in the amitriptyline group Wheatley 1997
  Pharmacokinetics of hypericin: 250, 750, & 1,500 micrograms orally to 13 healthy adults causes dose dependent rise in plasma to 1.3, 7.2, & 16.6 micrograms/liter with a halflife of 2 days Kerb 1996
  Meta-analysis of 23 trials with 1757 depressed patients shows Hypericum is about as effective as standard antidepressive treatment with far fewer side effects. More dropped out for placebo side effects than hypericum side effects Linde 1996
  Review of psychotropic applications of Ginkgo biloba, Hypericum perforatum, Valerian officinalis, and Panex ginseng Cott 1995
  Review of usage as antidepressive therapy Ernst 1995
  70% response rate (similar to chemical antidepressants) in a placebo-controlled, double-blind trial with 97 depression outpatients treated with 100 - 120 mg of hypericum extract bid Witte 1995
  Hypericum extract LI 160 was better than placebo in a 4 week study with 72 depressed patients. Hamilton depression score (HAMD) decreased more (21.8 to 9.2) than placebo (18.8 to 17.9) and response rate was 81% vs. 26% Hansgen 1994
  900 mg hypericum extract gave similar benefit and less side effects compared with 75 mg maprotiline in a study with 102 depressed patients Harrer 1994
  Meta-analysis of 25 controlled studies (15 with placebo) including 1592 depressed patients reveals dose was typically 300 - 900 mg/day of extract and duration 2 - 6 weeks Harrer 1994
  900 mg hypericum extract LI 160 was better than placebo in a 4 week study with 39 depressed patients Hubner 1994
  Randomized double-blind comparison of hypericum extract with maprotiline in 24 healthy volunteers showed similarity in EEG and improved cognitive functions mainly with hypericum Johnson 1994
  900 mg/day of LI 160 to 12 healthy older volunteers for 4 weeks showed increased deep sleep during the total sleeping period without hypostatic influence of the REM sleep phases (which is typical for tricyclic antidepressants and MAOI) Schulz 1994
  Hamilton Depression Scale fell from 15.8 to 7.2 by 900 mg/d hypericum extract for 4 weeks or to 11.3 in placebo group in a trial with 105 mildly depressed patients Sommer 1994
  Pharmacokinetics: 250, 750, or 1500 micrograms hypericin or 526, 1578, or 3156 micrograms pseudohypericin) to 12 healthy men results in plasma levels1.5, 4.1, 14.2 ng/mL for hypericin or 2.7, 11.7, 30.6 ng/mL for pseudohypericin; halflife 1 - 2 days Staffeldt 1994
  900 mg hypericum extract gave similar benefit and less side effects (fatigue 5%, restlessness 6%) compared with 75 mg imipramine in a study with 135 depressed patients Vorbach 1994
  A trial with 3250 patients (49% moderate, 46% intermediate) showed 30% improvement in 4-weeks of extract LI 160. 2.4% had undesirable effects: GI upset (0.6%), fatigue (0.4%), restlessness (0.3%) Woelk 1994
  LI 160 benefited 66.6% of depression outpatients compared with 26.7% in the placebo placebo group Schmidt 1993
  The Cochrane Library contains evidenced based systematic reviews prepared by the Cochrane Collaboration. Cochrane Library
Observational Studies/Case Reports
  The prevalence and perceived benefit of complementary and alternative medicine (CAM) use for perceived body-shape changes among a cohort of HIV-positive patients was investigated and several subjects reported using ginseng, St John's wort, etc. Cho 2006
  St. John's wort was prescribed 40 times in a 1-year prevalence study of 68,403 nursing home residents living in 557 nursing facilities throughout the United States. Harms 2006
  The fixed combination of black cohosh and St. John's wort extract is found to be superior to placebo in 301 women alleviating climacteric complaints, including the related psychological component. Uebelhack 2006
  It has been found that St John's wort extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals. Beattie 2005
  It is shown that short term administration of St John's wort extract significantly induce cytochrome P-450 3A4, it does not alter the concentrations of most circulating androgens in men and women but may produce a diminution in some of the circulating 5alpha-reduced androgens. Donovan 2005
  12 elderly subjects between the ages of 60 and 76 years, like their younger counterparts, are susceptible to herb-mediated changes in CYP activity, especially those involving St John's wort. Gurley 2005
  Ephedra was associated with 7 of the 13 possibly related cases, and caffeine was contained in 5 of these supplement products. Creatine, St. John's wort, and ginkgo biloba were other DS implicated in possibly related seizure events. Haller 2005
  A systematic review on large-scale observational studies of hypericum extracts in the treatment of depressive disorders reveals that hypericum extracts are well tolerated and seem to be effective in routine treatment of mild to moderate depressive disorders. Linde 2005
  Long-term users of certain supplements like garlic, ginkgo, ginseng, melatonin, soy, and St. John's wort (Hypericum perforatum) experienced less weight gain than individuals who did not use the supplements. Nachtigal 2005
  A 51-year-old woman had been having frightening suicidal and homicidal thoughts as a result of taking vitamin C and a herbal extract of St. John's wort. [Article in Dutch] Nanayakkara 2005
  It is shown that the combination of hypericin and UVA light increased the genotoxic burden, and the risk of significant photogenotoxic damage incurred by the combination of Hypericum extracts and UVA phototherapy may be low in the majority of individuals. Traynor 2005
  Review on antidepressants and pregnancy reveals that there exists no reservation against the use of St. John's wort during pregnancy and breastfeeding. [Article in German] Tschudin 2005
  Review on increasing trends in elderly persons' use of nonvitamin, nonmineral dietary supplements and concurrent use of medications reveals that for women, there was a significant linear trend over time for these 12 supplements including St John's wort. Wold 2005
  [In moderate depression. St. John's wort maintains effectiveness] [Article in German] [No authors listed] 2004
  Review on the safety and efficacy of herbal sedatives in cancer care reveals that milder sedatives or anxiolytics in need of clinical study include German chamomile, lavender, hops, lemon balm, and passionflower; St. John's wort may have anxiolytic effects with relevance to sleep. Block 2004
  Review on the use of antidepressant drugs in transplant recipients includes a brief discussion of St. John's wort and its impact on posttransplant drug therapy. Kim 2004
  Three case studies aimed at discovering the molecular targets responsible for Hypericum perforatum, Salvia divinorum, and Ephedra sinica actions are presented. Roth 2004
  Because of insufficient or conflicting evidence regarding the efficacy of conjugated linoleic acid, ginseng, psyllium, St. John's wort, etc. in weight loss, physicians should caution patients about the use of these supplements. Saper 2004
  [First-episode psychosis after taking an extract of Hypericum perforatum (St John's Wort).] Shimizu 2004
  Seventeen case reports associated the use of St. John's Wort with psychotic events was reported and in 12 instances, the diagnosis was mania or hypomania. Stevinson 2004
  The Hypericum extract was found to be devoid of effects of sedation, anticholinergic reactions, gastrointestinal disturbances and sexual dysfunction often found in patients treated with tricyclic antidepressants or selective serotonin reuptake inhibitors. Trautmann-Sponsel 2004
  In addition to a psychotherapeutic intervention or psychodynamic treatment or behavioral treatment, the first positive results of a psychopharmacological treatment regimen with opipramol and the St. John's Wort extract LI 160 has been reported. [Article in German] Volz 2004
  An 80-yrs old man, previously on long-term digoxin treatment, started consuming St John's wort(SJW) herbal tea(HT)(2,000 ml/daily) because of frequent episodes of depression. After cessation of consuming HT containing SJW, digoxin poisoning developed in our patient.[Article in Serbian] Andelic 2003
  A 23-year-old patient who had been taking St John's wort for postpartum depression for about 2 years was not recommended to use St John's wort during her pregnancy. Goldman 2003
  A case with premenstrual dysphoric disorder (PMDD) previously treated with selective serotonin reuptake inhibitors, was substituted with St. John's wort and much improvement in PMDD symptoms was noted for at least five-month follow-up. Huang 2003
  [St. John's wort in generalized anxiety disorder: three more case reports.] Kobak 2003
  Among 500 peri- and postmenopausal women outpatients between the ages of 40 and 60 years at the University of Illinois at Chicago clinics, botanical dietary supplements were used by 79% of respondents and St. John's wort were used by 7.34%. Mahady 2003
  [Hypertension induced by St. John's Wort - a case report.] Zullino 2003
  [Depression: St. John's wort is only effective after 2 to 3 weeks. Initial phase can be bridged with baldrian] [Article in German] [No authors listed] 2002
  [Study shows St. John's wort ineffective for major depression.] [No authors listed] 2002
  [St. John's Wort for depression. 900 mg per day should an effective dose] [Article in German] [No authors listed] 2002
  [Review: St. John's wort, ginkgo, saw palmetto, and kava may be effective for some conditions.] Baime 2002
  High-dose treatment with Saint John's wort extract induced CYP3A activity in healthy volunteers was evidenced by increased 6beta-hydroxycortisol excretion. Bauer 2002
  [Delayed emergence and St. John's wort.] Crowe 2002
  Reported case of mania induced by high doses of Hypericum perforatum in depressed woman with no past history of mania or hypomania and no concomitant use of antidepressants. Fahmi 2002
  Comparisons of presupplementation & postsupplementation ratios indicated that St John's wort induced activity of CYP2E1 and CYP3A4 (P <.0001). Among female subjects, St John's wort produced greater increases in CYP3A4 phenotypic ratios that appeared to be unrelated to body mass index. Gurley 2002
  Review on the peri-operative implications of herbal medicines indicates that an increasing number of patients are taking herbal medicines such as echinacea, garlic, ginkgo biloba, ginseng, St John's Wort, valerian, ephedra, kava, grapefruit juice and ginger. Hodges 2002
  Hyperforin is excreted into breast milk at a low level, hypericin is not. Both hyperforin and hypericin were below the lower limit of quantification in infant plasma. Klier 2002
  Evidence for alternative treatments for depression, anxiety, and insomnia are reviewed and treatment of depression with St. John's wort, L-tryptophan, 5-hydroxytryptophan, S-adenosylmethionine, dehydroepiandosterone, folate, exercise, acupuncture, and meditation are examined. Larzelere 2002
  Hypericum perforatum extract WS 5570 was found to be safe and more effective than placebo for the treatment of mild to moderate depression in male and female adult outpatients. Lecrubier 2002
  [St. John's Wort: more implications for cancer patients.] Mansky 2002
  It is shown that experienced physicians achieve virtually the same treatment results with suitable St. John's wort preparations as they do with modern synthetic antidepressants. [Article in German] Schulz 2002
  Review on gynecology shows that some evidence points to the efficacy of black cohosh, exercise, and possibly Kava and St. John's wort, in the treatment of menopausal symptoms. Sidani 2002
  Case of female patient with history of mild traumatic brain injury and resulting depression experiencing hypomania after adding SJW and Ginkgo biloba to her regimen of fluoxetine and buspirone. Spinella 2002
  [St John's wort was not better than placebo for reducing symptoms in major depressive disorder.] Swann 2002
  Comparision of the change in severity of depressive symptoms and occurrence of side effects in primary care patients treated with St John's wort (SJW) and sertraline shows that the more benign side effects of SJW make it a good first choice for this patient population. van Gurp 2002
  [For mild to moderate depression. Thesis paper recommends Hypericum] [Article in German] [No authors listed] 2001
  [Disappointing St. John's wort.] [No authors listed] 2001
  Drop in plasma cyclosporine was attributed to treatment with St John's wort. Beer 2001
  [Effectiveness of St. John's Wort in major depression apparently not indicated] [Article in German] Berner 2001
  A patient taking SJW developed a severe phototoxic reaction to laser light at 532 nm and also an exaggerated and unexpectedly severe response to pulsed dye laser light at 585 nm. Cotterill 2001
  [St. John's wort in generalized anxiety disorder: three case reports.] Davidson 2001
  A probable association between St. John's wort and elevated thyroid-stimulating hormone levels have been evaluated in 37 subjects. Ferko 2001
  [Is St John's wort a 'Prozac-like' herbal antidepressant?] Gobbi 2001
  Review on herbal medicines today and the roots of modern pharmacology indicates that many herbs have been evaluated in randomized, controlled trials, and several-St. John's wort and ginkgo, for example-are apparently effective. Goldman 2001
  23-year-old woman with no psychiatric history developed acute mania and psychosis while using a combination of valerian extract and hypericin. Guzelcan 2001
  Review on herbs and alternative therapies in the hypertension clinic reveals that herbals including ma huang, St. John's wort, yohimbine, garlic, and licorice all may cause important consequences in the hypertensive patient. Mansoor 2001
  [Vitamin C causes cancer! St. John's wort useless for depression!] Miller 2001
  [General practice research study of St. Johns Wort extract WS 5572. Normally 600 mg per day is enough] [Article in German] Rychlik 2001
  Review on herbal medicines and epilepsy indicates that St. John's wort has the potential to alter medication pharmacokinetics and the seizure threshold. Spinella 2001
  [Is St. John's wort safe in HIV?] Williams 2001
  "St. John's Wort and HAART " (no abstract) anon 2000
  SJW supplements caused subtherapeutic cyclosporine concentrations in a 29-year-old kidney and pancreas transplants recipient. Barone 2000
  Evidence based psychiatry & clinical examples Berner 2000
  Development of severe acute rejection 14 months after liver transplantation in 63-year-old patient was attributed to interaction between cyclosporin A and H. perforatum. Karliova 2000
  Re-calculating the sample size in internal pilot study designs with control of the type I error rate; Hypericum example Kieser 2000
  A kidney transplantation patient showed temporal relationship to hypericum extract comedication experienced as a sudden drop in her cyclosporin trough concentrations. Mai 2000
  "Experience with the treatment of depressive patients wtih deprim " (Russian, no abstract) Tochilov 2000
  Review of evidence for echinacea, garlic, ginger, ginkgo, St John's wort, and valerian Barrett 1999
  "A depressed man requesting St John's wort " (case report, review, no abstract) Ernst 1999
  Alternative therapies for advanced prostate cancer may include St John's Wort Moyad 1999
  St John's Wort may have use for depression associated with cancer Moyad 1999
  Interviews with 22 SJW users noted trend of belief in the need for personal control of health and self-diagnosis of "minor" depressed mood Wagner 1999
  Three of 4 adolescents who used Hypericum while under psychiatric care were reluctant to reveal this, believing the doctor would disapprove. Clinicians are advised to routinely ask about alternative medicine use Walter 1999
  Three nervines which have attracted considerable attention recently are St John's Wort, Gingko biloba and Valeriana officinalis. The extent of use for mental illness suggests that psychiatrists should become more knowledgeable about them Walter 1999
  Selective tumor-targeting by topical intralesional hypericin, 40-200 microgm, 3-5 times per week for a few weeks, for 19 patients (8 squamous cell & 11 basal cell). No necrosis was seen and new epithelium formed at the surface of the malignancy Alecu 1998
  "St John's wort during pregnancy" (no abstract) Grush 1998
  "St. John's wort: an alternative therapy in treating depression " (no abstract) Kupecz 1998
  ""Goodbye to the life I used to live" St. John's wort " (no abstract) Mack 1998
  "Can an herb really help depression?" (no abstract, review) Myers 1998
  "Hypomania and St John's wort" (no abstract) O'Breasail 1998
  "St. John's wort " (review, no abstract) Salzman 1998
  "St. John's wort and hypomania " (no abstract) Schneck 1998
  There is good evidence for the efficacy of St John's wort for the treatment of depression Wong 1998
  St John's wort shows promise as a treatment for depression so physicians should educate themselves and their patients about the efficacy and adverse interactions Zink 1998
  "St. John's wort: an herbal remedy for depression? " (no abstract) Evans 1997
  "St John's wort for depression " (no abstract) Houghton 1996
  Hypericin (polycyclic quinone) as a photosensitizer (632 nm activation) for a case of malignant mesothelioma Koren 1996
  A glioma that was treated with and developed resistance to radiation and tamoxifen was still sensitive to hypericin Zhang 1996
  The use of unconventional remedies among 63 HIV-positive men in California Dwyer 1995
  Staphylococci, shigellae & E. coli treatment with extract from oak cork, St. John's wort leaves & flowers and pine buds which may be useful for otorhinolaryngological diseases, enterocolitis in children and bacterial eczema Kolesnikova 1986
  Hypericum extract benefited 15 depressed women Muldner 1984
  Chronic colitis pains along the large intestine disappeared in 96% of 24 patients by the 15th day with a combination of Taraxacum, Hypericum, Melissa, Calendula officinalis and Foeniculum Chakurski 1981
  "Use of St.-John's-wort for the x-ray study of the large intestine " (Russian, no abstract) Omarov 1979
  "Treatment of suppurative infection with St. John's-wort and kalanchoe preparations " (Russian, no abstract) Kiriliuk 1977
  "Photodynamic action of extractum hyperici in the treatment of vitiligo" (no abstract, Polish) Nowak 1974
Traditional and Folk Use
  [Understanding St. John's wort.] [No authors listed] 2006
  St John's Wort products, which are approved for antidepressant use by the German drug agency, and tricyclic antidepressants (TCAs), accounted for more than 80% of antidepressant use in children and adolescents in Germany. Fegert 2006
  Reviews on the literature for alternatives to plant estrogens for menopausal symptoms indicates that St. John's wort can improve mood disorders related to the menopausal transition. Geller 2006
  The most important medicinal plants, including Ginkgo biloba, St John's wort, Kava-kava, Valerian, Bacopa monniera and Convolvulus pluricaulis, which are widely used for their reputed effectiveness in CNS disorders have been reviewed. Kumar 2006
  Herbs with safety issues, such as St John's wort, dong quai, and kava were used by Kansas and Wisconsin women, infants, and children participants. Lohse 2006
  Review on the evidence of efficacy of different types of Complementary and Alternative Medicine in depression indicates Grade 1 evidence on the use of St. John's wort, Tryptophan/5-Hydroxytryptophan, S-adenosyl methionine, Folate, Inositol, etc. Thachil 2006
  The potentially useful complementary medicines used in psychiatry include ginkgo and hydergine as cognitive enhancers, passion flower and valerian as sedatives, St John's wort and s-adenosylmethionine as antidepressants, and selenium and folate to complement antidepressants. Werneke 2006
  [St. John's wort in depression. The question is not whether it is effective but how do we use it.] [Article in German] Anghelescu 2005
  Effective psychoactive agents to self-treat many common psychiatric problems include 'medical' psycho-pharmacological agents such as analgesics and antihistamines, a plant extract called St. John's Wort (Hypericum), & physical treatments such as early morning bright light therapy. Charlton 2005
  St. John's wort has been shown to improve mild to moderate depression in the general population and appears to show efficacy for mood disorders related to the menopausal transition. Geller 2005
  Review on trends in ethnopharmocology shows that Ispaghula, Garlic, Ginseng, Ginger, Ginkgo, St. John's Wort, and Saw palmetto are a few examples of botanicals which are gaining popularity amongst modern physicians. Gilani 2005
  [St. John's wort for depression.] Malaty 2005
  [St John's for depression, worts and all.] Williams 2005
  [Monograph. Hypericum perforatum.] [No authors listed] 2004
  Soy, St. John's Wort, Silybum marianum, Ginkgo biloba, Citrus species, Vaccinum mirtillus, Hawthorn and tea are medicinal plants containing flavonoids whose efficacy in the treatment of a variety of diseases has been demonstrated in numerous clinical studies. [Article in Italian] Firenzuoli 2004
  Use of a syrup prepared from wild-growing grasses of the Far East including dog rose, herbs St. John's wort, parsley, Nettle and Laminal were studied in preventive maintenance of respiratory diseases and microelementoza at children. [Article in Russian] Kosolapov 2004
  The chemical diversity of spontaneous populations is one of the main directions of investigations on medicinal and aromatic plants and the target species under research includes Thymus spp., Hypericum spp., etc. [Article in Lithuanian] Radusiene 2004
  [Review: St John's Wort may be less effective than previously thought in people with depression.] Reddy 2004
  [Johanniskraut. Hypericum perforatum L.] [Article in German] Tschupp 2004
  A review on herbal supplement use among US women revealed that bivariate & multivariate analyses conducted to examine relationship between sociodemographic, health status & behavior characteristics & use of 1) any herbal supplement 2) Echinacea, Ginkgo biloba, ginseng, or St. John's wort. Yu 2004
  [Patient information. Straight talk about St. John's wort.] [No authors listed] 2003
  [From a 2500 year old apotropic comes a current antidepressive. The cultural history and mistique of St. John's wort] [Article in German] Czygan 2003
  St. John's wort, an unregulated herbal supplement widely used as a self-treatment for depression, can cause side effects and drug interactions. Deshmukh 2003
  [St. John's wort flowers and basis for use...] [Article in German] Dingermann 2003
  The historical background, active ingredients of St. John's Wort and the major double-blind placebo-controlled studies have been reviewed which shows that hypericum extracts are more effective than placebo for the treatment of mild to moderate depressive illness. Gupta 2003
  The certain & potential spectrum of internal & external uses of St. John's Wort includes gastro intestinal complaint & illness,skin disease, mucosal lesion, depressive upset & depression, restlessness, nervosity, convalescence, exhaustion, sleep disturbance & nursing treatment.[Article in German] Saller 2003
  A study was undertaken to investigate 500 registered nurses' knowledge about and use of five common herbal products such as ginkgo, St. John's wort, ginseng, garlic, and echinacea. Sand-Jecklin 2003
  Review on herbs commonly used by women reveals that St John's Wort is efficacious for treating mild to moderate depression but has many drug interactions. Tesch 2003
  It is proved that Hypericum is beneficial for the treatment of mild-to-moderate depression, with a very favorable side effect profile. Verotta 2003
  [Cancer, depression, and St. John's wort.] [No authors listed] 2002
  Review on the use of alternative medicine in the treatment of hepatitis C indicates that some patients with hepatitis C take St. John's Wort and ginger to treat the side effects caused by interferon therapy. Bean 2002
  [St John's wort and depression.] Cott 2002
  Review on the effectiveness of complementary and self-help treatments for depression indicates that the treatments with the best evidence of effectiveness are St John's wort, exercise, bibliotherapy involving cognitive behaviour therapy and light therapy (for winter depression). Jorm 2002
  The paper reviews current scientific data on the most important herbal substances including St. John's wort, kava, valerian, and gingko. [Article in German] Kalus 2002
  The efficacy of selected alternative treatments for unipolar depression including exercise, stress management techniques, acupuncture, St. John's wort, bright light, and sleep deprivation was reviewed. Manber 2002
  The efficacy and safety of Ginkgo biloba, St. John's wort, ginseng, Echinacea, saw palmetto and kava have been overviewed based on American experiences. [Article in Swedish] Mattsson 2002
  Review on alternative therapies for traditional disease states of menopause shows that the evidence for St. John's wort is equivocal. Morelli 2002
  St. John's wort is used in several therapeutic fields like neuropsychiatry, dermatology and in rheumatology. In herbal remedies and homeopathy, the flower heads are often prescribed as antidepressor in the treatment of mild to moderate depression. [Article in French] Neuman 2002
  [St John's wort as treatment for depression.] Oppel 2002
  Women and patients aged 40-60 yr were most likely to be taking a herbal product (P<0.05 and P<0.001 respectively). The most commonly used compounds were, in descending order, garlic, ginseng, ginkgo, St John's wort and echinacea. Skinner 2002
  An evidence-based review on herbs commonly used by women indicates that St John's Wort is efficacious for treating mild to moderate depression but has many drug interactions. Tesch 2002
  [Pharmacy through the ages. Hypericum perforatum.] Worthen 2002
  Data on the use of St. John's Wort, S-adenosyl-methionine, B vitamins, inositol, omega-3 fatty acids, & choline for mood disorders; data on the use of kava and other herbal agents & fish extract for anxiety and insomnia; and data on valerian and melatonin for insomnia were reviewed. Brown 2001
  [St. Johns wort--the mystery of change] [Article in Norwegian] Glad 2001
  In addition to antidepressant effect, new psychiatric uses for hypericum in obsessive-compulsive disorder, generalized anxiety disorder, menopausal symptoms, and alcohol dependence have been reported. Meltzer-Brody 2001
  FTC reaches settlements on AIDS claims for St. John's Wort.] Muris 2001
  The most frequently used nonvitamin, nonmineral dietary supplements products among college students were echinacea, ginseng, and St John's wort. Newberry 2001
  [St. John's wort for depression.] Ogletree 2001
  Review on herbal medicine shows that drugs such as St John's wort, ginkgo, saw palmetto have sufficient clinical studies to consider orthodox use. Pinn 2001
  Examination of the rate of utilization of complementary and alternative medicine (CAM) in Amish women, indicates that ten pregnant Amish women reported using echinacea, St. John's Wort, red clover, garlic and ginseng. von Gruenigen 2001
  Survey of 43 SJW users indicates most take it for depression, 74% without medical advice. 36 report benefit; 20 report side effects. Mean dosage=475 mg/day (300-1200), mean duration=7.3 weeks (1 day -5 yr) Beckman 2000
  The history of transitioning from being considered alternative to being orthodox remedies indicates that suggestions for greater regulation and licensing of herbal remedies will increase healthcare costs so should only be done selectively Ashcroft 1999
  Of 20 toothbrush sticks from Ethiopia, only Agave sisalana, Birbira & Hypericum revolutum showed weak toxicity to brine shrimp while all were antibacterial against Staphylococcus aureus and Bacillus cereus Kassu 1999
  "Hypericum perforatum L., St. John's wort, a medicinal plant in folk medicine " (German, no abstract) Kopp 1999
  Review of nine nutrient and herbal remedies commonly used for diabetes Mozersky 1999
  In 1996 131.5 million daily doses of preparations containing extracts of Hypericum perforatum L. were prescribed in Germany for treating mild to moderately severe depressive disorders Orth 1999
  [Listening to St. John's wort.] [No authors listed] 1997
  Of 21 Nepalese medicinal plants the methanol extracts from Hypericum, Lygodium & Maesa were effective in assays against 3 viruses Taylor 1996
  "Han-lian-cao" a Taiwanese drug derived from Wedelia and Hypericum Chen 1992
  Sarothralin G: a new antimicrobial compound from Hypericum japonicum, contains phloroglucinol and filicinic acid moieties. It is used traditionally for infectious hepatitis, bacterial diseases, gastrointestinal disorders, and tumors Ishiguro 1990
  Traditional antileukodermic herbal recipes Capitanio 1989
  Folk use of mint, thyme, red juniper, Hypericum in northwestern Greece coincides with usage elsewhere in the Mediterranean region Tammaro 1986
         Monograph in "A Modern Herbal" by Mrs. M. Grieve at botanical.com
         Type "Hypericum perforatum" in the search field of D. Moerman's Native American Ethnobotany
         Search for ethnobotanical uses of Hypericum in Dr. Duke's Phytochem and Ethnobot DB
SAFETY DATA
 
Adverse Effects & Toxicity
  Hyperforin, an acylphloroglucinol compound, isolated from Hypericum perforatum, may be useful to decrease amyloid burden and toxicity in Alzheimer's disease patients, and may be a putative therapeutic agent to fight the disease. Dinamarca 2006
  Among the identification of 34 studies of variable methodologic quality on anti-depressive therapies after heart transplantation, St John's wort, an alternative herbal drug, has been associated with life-threatening immunosuppression. Fusar-Poli 2006
  In a 48-year-old female patient, acute hepatitis with transaminase increase inconspicuous hepatitis serology findings, negative autoantibody status & negative virus serology was observed after a 10-week intake of kava-kava (1-3 x 200 mg/day) & St John's Wort (1 x 425 mg/day). [Article in German] Musch 2006
  Hypericin combined with Hypericum perforatum extracts or constituents exert less phototoxicity than pure hypericin, possibly not through a reduction in arachidonic acid peroxidation. Schmitt 2006
  All extracts of Hypericum perforatum exhibited significant cytotoxicity, those prepared in ethanol showed between 7.7 and 77.4% cell survival, whereas the chloroform and hexane extracts showed approximately 9.0 (p < 0.0001) and 4.0% (p < 0.0001) survival. Schmitt 2006a
  The toxicity of Hypericum perforatum administered to female rats during organogenesis (9th to 15th day of pregnancy) was evaluated. H. perforatum does not seem to be toxic with 36 mg/Kg body weight of Jarsin dried extract administered in 0.5 ml of saline. [Article in Portuguese] Borges 2005
  Hypericum perforatum does not seem to be toxic to mother Wistar rats or to interfere with the progress of gestation during organogenesis. Borges 2005a
  A 22-year-old man who had taken 1000 mg/day of flowering herbs of Hypericum perforatum L, for treatment of depression had severe hematologic toxicity, with conditions involving bone marrow necrosis. Demiroglu 2005
  Aerobic exercise, St. John's wort (SJW), and S-Adenosylmethionine have considerable empirical support in otherwise healthy persons, but SJW may have undesirable side effects for coronary heart disease patients. Lett 2005
  The nature and mechanism of action of the phytochemicals presently receiving increased attention in the field of food toxicology was described which relates to 17 compounds including beta-carotene, coumarin, anisatin, St. John's wort ingredients. Rietjens 2005
  [Review: hypericum extracts are safer and lead to fewer adverse effects than older standard antidepressants, but have similar tolerability to SSRIs.] Valerio 2005
  It is shown that the complementary and alternative medicinal agents including angelica, German chamomile flower, ephedra, gingko, grape seed extract, licorice root, St. John's wort, kava kava rhizome, peppermint, stinging nettle, and ginseng, are also associated with significant adverse effects. Bielory 2004
  The effects of a treatment with hypericum administered prenatally and during breastfeeding was investigated in Wistar rats which revealed a severe damage in the livers and kidneys of treated animals. Gregoretti 2004
  Exposure of human lens epithelial cells to 0.1-10 microM hypericin and irradiation with 4 J/cm2 UV-A or 0.9 J/cm2 visible light shows that ingested St. John's Wort is potentially phototoxic to the eye and could contribute to early cataractogenesis. He 2004
  Data from 35 double-blind trials showed that dropout & adverse effects in patients receiving hypericum extracts were similar to placebo, lower than with older antidepressants, & selective serotonin reuptake inhibitors suggesting that hypericum extracts are well tolerated & safe. Knuppel 2004
  The literature on the potential risks of commonly used herbal medications of Ginkgo Biloba, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, Garlic, Kava and Ephedra was reviewed. [Article in Hebrew] Zlotogorski Hurvitz 2004
  Some of the more noteworthy medicinal plants for which neurological toxicity has been reported are Hypericum perforatum, kava kava (Piper methysticum), Aconitum sp. and Callilepis laureola. [Article in Spanish] Carod Artal 2003
  [Suspected withdrawal syndrome after cessation of St. John's wort.] Dean 2003
  A brief description of pharmacodynamics and clinical applications, followed by a systematic review of adverse effects, toxicity, and drug interactions have been presented. Hammerness 2003
  [Adverse drug effects and interactions. What is the current thinking about the use of St. John's wort?] [Article in German] Johne 2003
  Some adverse side-effects connected with the plant, Saint-John's-wort includes photosensitivity, and the interactions with other drugs or foodstuffs. [Article in Slovak] Kapusta 2003
  [Hypericum perforatum L. and Chamomilla recutita (L.) Rausch.--accumulators of some toxic metals.] Kral'ova 2003
  Photosensitivity, an abnormal skin reaction to light, is a rare adverse event associated with herbal medicine use and case reports in the literature most commonly implicate St. John's wort. Palanisamy 2003
  Some of the side effects of Hypericum perforatum extracts like nausea, rash, fatigue, restlessness, photosensitivity, acute neuropathy, and even episodes of mania and serotonergic syndrome when administered simultaneously with other antidepressant drugs have been reviewed. Rodriguez-Landa 2003
  Current research findings suggest that St. John's wort may be an effective treatment for mild depression; however, evidence of significant adverse drug interactions with St. John's wort should not be overlooked. Boehnlein 2002
  A case of mania induced by high doses of Hypericum perforatum in a 28-year-old depressed woman with no past history of mania or hypomania and no concomitant use of antidepressants was reported. Fahmi 2002
  The herbs, identified on the basis of California Poison Control System-San Francisco division call frequency were: St John's wort, ma huang, echinacea, guarana, ginkgo, ginseng, valerian, tea tree oil, goldenseal, arnica, yohimbe and kava kava. Haller 2002
  [Hypertensive crisis associated with St. John's Wort.] Patel 2002
  Adverse reactions to Hypericum extract in the clinical treatment of depression include skin reddening and itching, dizziness, constipation, fatigue, anxiety, and tiredness. [No authors listed] 2001
  A patient who developed a severe phototoxic reaction to laser light at 532 nm and also an exaggerated and unexpectedly severe response to pulsed dye laser light at 585 nm is described. It subsequently transpired that the patient was taking St John's Wort at the time of laser treatment. Cotterill 2001
  A 23-year-old lady with no psychiatric history developed acute mania & psychosis while using St. John's wort at a high dosage (Valdispert 'balans', a combination of valerian extract & hypericin) & she was diagnosed as having substance-induced mood disorder, with mania. [Article in Dutch]. Guzelcan 2001
  St John's wort may cause serotonin syndrome in sensitive patients. Parker 2001
  Review of incidence and clinical relevance of the interactions and side effects of Hypericum preparations. Schulz 2001
  [St. John's Wort warning.] [No authors listed] 2000
  [St. John's Wort linked to kidney rejection.] [No authors listed] 2000
  "Drug interactions with st. John's wort " (no abstract) anon 2000
  Case of a patient who developed depression following bilateral orchidectomy for cryptorchidism, taking both SSRI & Hypericum who developed a manic episode where testosterone replacement might have been affected Barbenel 2000
  "Acute St. John's wort toxicity " (case report, no abstract) Brown 2000
  "Photosensitivity associated with herbal preparations of St John's wort " (letter, no abstract) Lane-Brown 2000
  "From the Food and Drug Administration " (no abstract) news 2000
  "Patients being treated for HIV should avoid St. John's Wort: NIH " (no abstract) news item 2000
  "Drug interactions with Hypericum. Is nature not so mild after all? " (German, no abstract) Roots 2000
  Minimal erythema dose of Hypericum oil (hypericin 110 microg/mL) or ointment (hypericin 30 microg/mL) on forearm of 16 people was unchanged by visual score but some increase seen with the more sensitive photometric measurement Schempp 2000
  Adverse events for fluoxetine were 23%: agitation (8%), GI disturbances (6%), retching (4%), dizziness (4%), tiredness, anxiety/nervousness & erectile dysfunction (3% each); and 8% for Hypericum: GI disturbances (5%) in a clinical trial with 240 patients Schrader 2000
  "Herbal supplements and prescription drugs. A risky combination? " (news, no abstract) Stein 2000
  Bromodeoxyuridine incorporation into keratinocyte DNA was decreased by hypericin (>50 microgm/mL) with visible (2.6 mumol/m2s) or UVA (1 J/cm2), but not UVB (150 mJ/cm2) light. Absorbance spectrum of Hypericum extract has maxima in the whole UV range Bernd 1999
  "St. John's Wort: is it effective and harmless? " (no abstract) Biron 1999
  Common culprits of phytophotodermatitis are Umbelliferae, Rutaceae, and Moraceae and St John's Wort Bowers 1999
  Review of phytophotodermatitis by common culprit plant families of Umbelliferae, Rutaceae, Moraceae & St. John's Wort; including the mechanism involved, clinical features, and treatment options Bowers 1999
  "Second thoughts about safety of St John's wort" Case reports affecting blood levels for 1 patient on theophylline, 3 on cyclosporin, 1 on warfarin, 3 on ethinylestradiol/desogestrel raise the possibility of regulation (comments in Feb 12 Lancet) Ernst 1999
  "Toxicity of Hypericum perforatum " (case report, no abstract) Firenzuoli 1999
  "Safety of Hypericum perforatum " (letter, no abstract) Firenzuoli 1999
  Of 30 HIV patients who tried hypericin (0.25 or 0.5 mg/kg i.v. 2-3 times weekly, or 0.5 mg/kg/d orally) 16 discontinued early because of toxic effects. Severe cutaneous phototoxicity was seen in 11. Virologic markers did not significantly change Gulick 1999
  Hypericin (40 mg/kg i.p.) with light (108 J/cm2) was lethal to mice. Erythema, desquamation & erosions resulted from hypericin-solketal ointment with light (> 4.5 J/cm2). There is potential for treating psoriasis Kamuhabwa 1999
  Hypericin was only slightly photogenotoxic to V79 cells Kersten 1999
  Photofrin II & mTHPC induced photosensitivity is reversed by hypericin in Staphylococcus aureus Kubin 1999
  Two cases of mania temporally associated with the use of St. John's wort suggesting evaluation of its propensity to cause affective switching is needed Nierenberg 1999
  Sperm motility was inhibited by high concentration (0.6 mg/mL) of St. John's wort. Also by saw-palmetto, echinacea & gikgo Ondrizek 1999
  Pretreatment of oocytes with 0.6 mg/mL of St. John's wort resulted in zero sperm penetration and denatured DNA. A lower concentration (0.06 mg/mL) had no effect. Echinacea and Ginkgo were also imhibitory. Saw palmetto had no effect Ondrizek 1999
  Intracutaneous application of 100 ng/ml hypericin gives no phototoxic reaction. Hypericin has Abs peaks of 330, 550 & 588 nm. PDT 1200 SOA (520-750 nm) is four (in vitro) or ten times (in vivo) more effective than a 1000 watt solar simulator (290-2500 nm) Schempp 1999
  Ma huang, St. John's wort, and kava are examples of readily available psychotropic herbs with the potential for negative effects Tinsley 1999
  "Acute neuropathy after exposure to sun in a patient treated with St John's Wort " (no abstract) Bove 1998
  A case of stinging pain in the face & hands after taking 500 mg/d Hypericum for 4 weeks. Symptoms began to clear after 3 weeks and were gone in 2 months Bove 1998
  "Beware "St. John's Wort," potential herbal danger " (no abstract) Ciordia 1998
  A systematic review of adverse drug reactions of Hypericum found some gastrointestinal symptoms, dizziness/confusion and tiredness/sedation with an incidence similar to that of placebo. Photosensitivity is extremely rare Ernst 1998
  Albumin extensively inhibits the photocytotoxic effect of pseudohypericin against A431 tumour cells Vandenbogaerde 1998
  Case report of depression patient taking St. John's Wort-extract for three years having itching erythematous lesions in light-exposed areas Golsch 1997
  A 4-week trial with 3250 patients showed 30% improved, 2.4% had undesirable effects: gastrointestinal irritations (0.6%), allergic reactions (0.5%), tiredness (0.4%), and restlessness (0.3%) Woelk 1994
  Sheep experimentally poisoned with Hypericum perforatum had lower hemoglobin, RBC, glucose, cholesterol, alk. phosphotase and higher BUN, bilrubin, aminotransferase, etc Kako 1993
  A case of St. John's wort photosensitization poisoning in sheep is given Kumper 1989
Interactions
  Significant interactions of St. John's wort include decreased efficacy of antiretrovirals, cyclosporine, tacrolimus, antiepileptics, irinotecan, and other chemotherapeutic agents. Adverse events include nausea, headache, constipation, dizziness, confusion, fatigue and dry mouth. [No authors listed] 2006
  [HIV patients taking antiretrovirals should avoid garlic, St. John's wort. Other health products were fine.] [No authors listed] 2006
  St John's wort, a popular herbal antidepressant, increases clearance of many drugs, and abnormally low cyclosporine, digoxin, theophylline, or protease inhibitor concentrations may be observed in a patient taking any of these drugs in combination with St John's wort. Dasgupta 2006
  Co-medication with St John's Wort resulted in decreased plasma concentrations of a number of drugs including amitriptyline, cyclosporine, digoxin, indinavir, irinotecan, warfarin, phenprocoumon, alprazolam, dextrometorphane, simvastatin, and oral contraceptives. Madabushi 2006
  Some complementary and alternative medicines like kava-kava, vitamin E, quercetin, ginseng, garlic, beta-carotene, and Echinacea are capable of causing interactions with anticancer drugs. Meijerman 2006
  It has been reported that the interactions between drugs and grapefruit juice or St John's wort are frequent. [Article in Spanish] Morales-Olivas 2006
  St John's wort (SJW) found to decreases the blood concentration of ciclosporin A (CsA), which may result in allograft rejection and an optimal dosage regimens of CsA during and after the intake of SJW to prevent an adverse drug interaction between CsA and SJW was identified. Murakami 2006
  St. John's Wort preparations should not be taken concurrently with other antidepressants, with coumarin-type anticoagulants, immuno-suppressants cyclosporine and tacrolimus, protease & reverse transcriptase inhibitors used in anti-HIV treatment or with certain antineoplastic agents. Schulz 2006
  St John's wort was the first and most frequently reported source of induction-style herb-drug interactions and this type of interaction is likely to be relevant to other herbal products. Tirona 2006
  Several herbal medicines including Echinacea, garlic, ginkgo, milk thistle, and St. John's wort have the potential to cause significant interactions with antiretroviral drugs. van den Bout-van den Beukel 2006
  It has been shown that since Ginkgo and onion contain quercetin and its glycosides as St. John's Wort and the coadministration of cyclosporin with ginkgo or onion may be subject to clinically relevant interactions as St. John's Wort. Yang 2006
  [Herb-drug interactions. St. John's wort and prescription medications.] Bressler 2005
  Review on interaction of warfarin with drugs, natural substances, and foods reveals that St. John's wort and possibly some ginseng formulations may have the potential to diminish warfarin anticoagulation, apparently by inducing CYP2C9 activity. Greenblatt 2005
  Interactions are likely between herbal remedies with antiplatelet or nephrotoxic effects and NSAIDs, hepatotoxic herbal remedies and disease-modifying antirheumatic medication, and between St. John's Wort and cyclosporin. Holden 2005
  Toxicity and drug interactions associated with herbal products like ephedra and St. John's Wort have been reviewed. Holstege 2005
  Review on herb-drug interactions revealed that St. John's Wort decreased blood concentrations of ciclosporin, midazolam, tacrolimus, amitriptyline, digoxin,indinavir, warfarin, & theophylline, but did not alter pharmacokinetics of carbamazepine, pravastatin, mofetil mycophenolate & dextromethorphan. Hu 2005
  Through induction of cytochrome P450 enzymes and/or P-glycoprotein, St John's wort has been shown to lower plasma concentration (and/or pharmacological effect) of a number of conventional drugs, including cyclosporine, indinavir, irinotecan, nevirapine, oral contraceptives & digoxin. Izzo 2005
  Gum guar, St. John's wort, Siberian ginseng and wheat bran were found to decrease plasma digoxin concentration. Decreased plasma concentration of simvastatin or lovastatin was observed after co-administration with St. John's wort and wheat bran, respectively. Izzo 2005a
  Review on clinical trials examining natural health product-HIV drug interactions and their methodological characteristics reveals that significant interactions were observed with St John's wort, garlic and vitamin C. Mills 2005
  Potentially clinically significant drug interactions were observed with St. John wort (16/24 studies), garlic (2/5 studies), and American ginseng (1 study). Mills 2005
  St. John's Wort (SJW) is associated with increased metabolism of norethindrone and ethinyl estradiol, breakthrough bleeding, follicle growth and ovulation & the women using oral contraceptives should be cautioned that SJW might interfere with contraceptive effectiveness. Murphy 2005
  Investigation of the time-dependent effects of St. John's wort (SJW) on midazolam 1-hydroxylation in Wistar rats shows that it is important for persons receiving SJW for an extended time to consider its interactions with prescription drugs. Qi 2005
  Hyperforin is an active ingredient of the herbal remedy St. John's wort, and activates gene transcription of cytochrome p450-3A4, causing significant botanical-drug interactions. Shay 2005
  There is very little evidence to substantiate actual pharmacokinetic and/or pharmacodynamic interaction between drugs and kava or St. John's wort. Singh 2005
  Only a few herbal drugs have been cited in interaction reports, for e.g.St John's Wort, Ginkgo biloba, Dan Shen,liquorice,Ma huang & garlic, & main drugs involved are those which are already susceptible to interactions with many other drugs, such as warfarin, protease inhibitors & anti-cancer drugs. Williamson 2005
  [St John's wort-associated drug interactions: short-term inhibition and long-term induction?] Xie 2005
  St John's wort reduces the efficacy of several drug groups including: immunosuppressants (risk of graft rejection), oral contraceptives (risk of pregnancy), oral anticoagulants (risk of thrombosis), and HIV protease inhibitors. It can also reduce the bioavailability of digoxin. [No authors listed] 2004
  Clinically significant drug interactions of Atazanavir, the first once-daily protease inhibitor for the treatment of human immunodeficiency virus type 1 infection, include antacids, diltiazem, St. John's wort, and warfarin. Busti 2004
  A total of 16.6% of children had a current or past history of ingestion of herbal medicines. A significant number of children had taken agents which may interact with anesthesia and surgery: St John's Wort, valerian, garlic and gingko. Crowe 2004
  Review on food-drug interactions via human cytochrome P450 3A indicates that grapefruit juice interacts with felodipine and cyclosporine, red wine with cyclosporine, and St John's wort with various medicines including cyclosporine. Fujita 2004
  When combined with serotonin reuptake inhibitor, antidepressants or buspirone, St John's wort can cause serotonergic syndrome. Izzo 2004
  Hyperforin content of St John's wort (SJW) extracts significantly affects the extent of the pharmacokinetic interaction between cyclosporine and SJW. Mai 2004
  Combinations of St John's wort with serotonergic agents and other antidepressants should be restricted to prescription-only, by experienced clinicians, due to potential central pharmacodynamic interactions. Mannel 2004
  Systematic review of clinical trials on interactions of St John's wort with conventional drugs indicates that Clinicians and patients should beware of possible decreases in the systemic bioavailability of conventional drugs when taken concomitantly with St John's wort. Mills 2004
  Black lipid membrane experiments were performed to investigate the effect of the ethanolic Hyperici herba extract on the electrical properties of artificial lipid bilayers. Neagoe 2004
  [Induction of imatinib metabolism by hypericum perforatum.] Smith 2004
  Coadministration of imatinib with St. John's wort in ten healthy adult volunteers may compromise imatinib's clinical efficacy. Smith 2004
  Herbs with the potential to significantly modulate the activity of drug-metabolizing enzymes and/or the drug transporter P-glycoprotein include garlic, ginkgo, echinacea, ginseng, St John' s wort and kava. Sparreboom 2004
  St John's wort was found to induce both CYP3A4-catalyzed sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole and enormously decreases the plasma concentrations of omeprazole, in 12 healthy adult men. Wang 2004
  Investigation of possible interactions of St John's wort extract & its constituents with transport activity of P-Glycoprotein (Pgp) suggests that plasma levels of constituents of St John's wort are very likely too low to interfere with Pgp at blood-brain-barrier with possible exception of quercetin. Weber 2004
  It is indicated that Hypericum perforatum, an increasingly used herbal antidepressant drug should be used with caution due to severe and possibly dangerous interaction with cardioactive drugs. Zellweger 2004
  St John's wort decreased the plasma concentration of the active metabolite SN-38 in cancer patients receiving irinotecan treatment. It caused breakthrough bleeding and unplanned pregnancies when used concomitantly with oral contraceptives. Zhou 2004
  Various herbal supplements have been reported or are suspected to interact with certain oral health drugs, the most important one being kava, St. John's wort, chamomile, and valerian interacting with central nervous system (CNS) depressant drugs. Abebe 2003
  [Drug interaction of herbal tea containing St. John's wort with cyclosporine.] Alscher 2003
  Review on drug-herb interaction among commonly used conventional medicines, indicates that warfarin was the most common drug and St. John's wort was the most common herbal product reported in drug-herb interactions. Brazier 2003
  Drugherb interactions can result in unexpected concentrations of therapeutic drugs. For example, low concentrations of several drugs (e.g., cyclosporine, theophylline, digoxin) can be observed in patients who initiated self-medication with St John's wort. Dasgupta 2003
  Prescription of St. John's wort might decrease methadone blood levels and induce withdrawal symptoms which, if not correctly identified and handled (by changing the antidepressant or by increasing the methadone dose), might cause unnecessary discomfort to the patient. Eich-Hochli 2003
  Interactions of grapefruit juice with cyclosporin and felodipine, St John's wort with cyclosporin and indinavir, and red wine with cyclosporin, have the potential to require dosage adjustment to maintain drug concentrations within their therapeutic windows. Harris 2003
  The pharmacology of irinotecan is complicated by existence of genetic inter-individual differences in activation and deactivation enzymes of irinotecan (e.g., CYP3A4, CYP3A5, UGT1A1) & sharing competitive elimination pathways with many concomitant medications, including St. John's Wort. Ma 2003
  Administration of St. John's wort extract to patients receiving tacrolimus (TAC) treatment can result in a serious drug interaction leading to reduced TAC blood concentrations associated with risk of organ rejection. But mycophenolic acid pharmacokinetics remained unaffected with hypericum. Mai 2003
  Review on current St John's wort (SJW) research from mode of action to clinical efficacy confirmed the good tolerability of St. John's wort extract and the very low frequency of adverse events, however, some drug interactions have been found to occur with SJW extract. Muller 2003
  It is suggested that most of the potential deleterious effects of natural products on unborn may be related to hormonal effects (e.g., phytoestrogens) and nutriceutical drug interactions (e.g., St. John's Wort & antidepressants), rather than direct embryotoxicity per se. Rousseaux 2003
  [Dangerous interaction of St. John's wort with chemotherapy?] [Article in German] Schmitt 2003
  [Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception.] Schwarz 2003
  Interactions between the herb St John's wort and the drugs such as cyclosporin, anticoagulants, digoxin, antidepressants and protease inhibitors have been reported. Williamson 2003
  Review on herbal interactions with cardiovascular drugs reveals that some herbs, including garlic, ginkgo, ginseng, and St John's wort, can have a significant influence on concurrently administered drugs. Awang 2002
  St. John's Wort may potentiate certain enzymes of the cytochrome P450 enzyme system which resulted in a lowering of serum concentration of a number of concomitant drugs, including warfarin, digoxin, theophylline, cyclosporin, and indinavir. Bilia 2002
  [Tacrolimus-induced nephrotoxicity unmasked by induction of the CYP3A4 system with St John's wort.] Bolley 2002
  [Possible serotonin syndrome after combination of buspirone and St John's Wort.] Dannawi 2002
  St. John's wort is efficacious for mild to moderate depression, but serious concerns exist about its interactions with several conventional drugs. Ernst 2002
  5 independent computerized literature searches of reports of interactions of SJW with cyclosporine showing that SJW can endanger organ transplantations. Ernst 2002
  St John's wort, for example, induces the expression of p-glycoprotein and CYP3A4 in liver and intestine and thereby decreases the activity of other drugs. [Article in German] Fattinger 2002
  A number of clinically significant interactions of St John's wort have been identified with prescribed medicines including warfarin, phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin & oral contraceptives resulting in a decrease in concentration or effect of medicines. Henderson 2002
  H. perforatum increased P-glycoprotein expression, P-glycoprotein mediated rhodamine efflux, and attenuated Ritonavir inhibited P-glycoprotein mediated efflux. Hennessy 2002
  [Interactions of the oral contraceptive pill with antibiotics and St John's wort: knowledge of female college students.] Hindmarch 2002
  Review of recent studies on interactions between SJW and other drugs including cyclosporine, indinavir, nevirapine, oral contraceptives, and amitriptyline. Ioannides 2002
  An evidence-based literature review of 5 commonly used herbs in Denmark: St John's wort, ginkgo biloba, valerian, garlic, and ginseng has been presented. Attention to clinical practice & recommendations for discontinuation of the 5 herbs are given before surgery. [Article in Danish] Kistorp 2002
  If inducers (e.g. rifampicin, anticonvulsants, St John's wort) or inhibitors (ketoconazole, grapefruit juice, etc.) of CYP3A4 are concomitantly administered pharmacokinetic interactions could be expected to a variable extent. Klotz 2002
  Patients on irinotecan treatment should refrain from taking SJW because plasma levels of SN-38 were dramatically reduced. Mathijssen 2002
  St. John's wort has been implicated as an inducer of the P450 enzyme system, and as such, may cause increased metabolism of certain drugs, including oral contraceptives. Women using oral contraceptives have been warned against using St. John's wort. Murphy 2002
  Natural products that have been reported to interact with drugs in humans include coenzyme Q10, dong quai, ephedra, Ginkgo biloba, ginseng, glucosamine sulfate, ipriflavone, melatonin, and St. John's wort. Scott 2002
  [Taking St. John's wort with other drugs can be trouble.] [No authors listed] 2001
  Review on interactions of herbal remedies with prescription cardiovascular medications shows that limited data exists regarding the efficacy of herbs such as echinacea, garlic, ginseng, gingko, ephedra, and St. John's wort. Aggarwal 2001
  Review on the use of alternative pharmacotherapy (AP) in management of cardiovascular disease (CVD) indicates that some APs interact with common prescription CVD medications (eg, gingko and ginseng with warfarin, St. John's Wort with digoxin). Chagan 2002
  Studies have shown that St. John's wort (SJW) (Hypericum perforatum) can reduce plasma levels of indinavir, cyclosporin, digoxin, and possibly other drugs as well. It has been reported that the P-glycoprotein transmembrane pump is also induced by SJW. Cott 2001
  Review on herb-drug interactions and assessment of report reliability shows that among 180 cases of suspected interactions, warfarin was the most common drug (18 cases) and St John's wort the most common herb (54 cases) involved. Fugh-Berman 2001
  St John's wort lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon & theophylline & it causes intermenstrual bleeding, delirium or serotonin syndrome, when used with oral contraceptives, loperamide or serotonin-reuptake inhibitors. Izzo 2001
  Psychopharmacologic interventions in transplant patients, including the use of antidepressant medication pre- & post-transplant, and interactions between over-the-counter and herbal agents (e.g., St. John's Wort) and immunosuppressive agents have been reviewed. Jowsey 2001
  Examples of conventional medications which may undergo significant CYP 3A4 induction by St. John's wort include cyclosporine, indinavir, and oral contraceptives. Markowitz 2001
  A kidney transplant recipient who developed marked reduction of cyclosporine therapeutic activity after the self-initiation of St. John's wort has been described. Moschella 2001
  A kidney transplant recipient developed marked reduction of cyclosporine therapeutic activity after the self-initiation of St. John's wort. Moschella 2001
  Reported case of irregular bleeding with oral contraception and SJW and discussion of drug interactions and the mechanisms. Ratz 2001
  SJW decreases plasma concentrations of simvastatin but not of pravastatin probably due to the enhancement of the CYP3A4-mediated first-pass metabolism of simvastatin in the small intestine and liver. Sugimoto 2001
  Many commonly ingested substances such as grapefruit juice and Hypericum perforatum (St John's wort) have been found to interact with important therapeutic agents such as cyclosporine. Tsunoda 2001
  2 kidney transplant recipients started self-medicating with St John's wort causing significant reduction in cyclosporine concentrations. Turton-Weeks 2001
  St. John's Wort can induce the CYP3A family of activation enzymes through which approximately 50% of drugs are metabolized. This poses some risk of inadvertently reducing the half-life of such drugs as indinavir, cyclosporin and cyclophosphamide. Wargovich 2001
  Herbs like Ginkgo biloba, Piper methysticum (Kava-Kava), Glycyrrhiza glabra, Hypericum perforatum, Valeriana officinalis, Cannabis sativa, Salix alba, etc. have been included for the study of synergy and other interactions in phytomedicines. Williamson 2001
  [Toxicity. St. John's wort--interactions with indinavir and other drugs.] [No authors listed] 2000
  Review of reported interactions and reduced therapeutic activity with warfarin, cyclosporin, oral contraceptives, theophylline, fenprocoumon, digoxin & indinavir. Sudden discontinuance of hypericum may cause a rebound effect Baede-van Dijk 2000
  "Drug interaction of St John's wort with cyclosporin " (letter, no abstract) Breidenbach 2000
  Cyclosporin blood level fell 47% in 35 kidney transplant patients taking St. John's Wort. Cyclosporin dose was increased 46% to compensate and on discontinuation of the herb cyclosporin bounced up 187% Breidenbach 2000
         Risk of drug interactions with St. Johnswort and Indinivar and other drugs. FDA Center for Drug Evaluation and Rearch Public Health Advisory
  Review finds decreased bioavailability of digoxin, theophylline, cyclosporin & phenprocoumon when combined with St John's wort and mild serotonin syndrome when combined with SSRI. Many interactions reports are sketchy and lack lab analysis Fugh-Berman 2000
  [St John's wort and drugs: what nurses need to know. Harding-Price 2000
  "Pericon interactions " (Danish, no abstract) Jensen 2000
  "Harmless herbs: a cause for concern? " (letter, no abstract) Koupparis 2000
  Effect of Hypericum on P-450 was probed by urinary dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) in 7 people. No significant differences were found Markowitz 2000
  Editorial summarizes reports of Hypericum's inhibition of CYP3A4 &/or p-glycoprotein and calls for a sense of proportion - keeping in mind that many ordinary fruits & vegetables have similar effects McIntyre 2000
  "Interaction between indinavir and St. John's wort reported " (news report of Piscitelli) Miller 2000
  Hyperforin is a potent ligand (K(i)=27 nM) for the pregnane X receptor, a nuclear receptor that regulates expression of CYP3A4 monooxygenase. Hyperforin induces CYP3A4 expression in human hepatocytes Moore 2000
  "St. John's Wort: three cases of possible mania induction " (no abstract) Moses 2000
  Antiimmobility effect of dry extract containing 0.3% hypericin & 3.8% hyperforin is completely suppressed by rimcazole pretreatment and reduced by 5, 7-dihydroxytryptamine in rats Panocka 2000
  Indinavir (AIDS drug) plasma level area under the curve (AUC) was reduced 57% in 16 healthy volunteers after two weeks of 900 mg/d St John's Wort (0.3% hypericin) Piscitelli 2000
  Urinary 6-beta-hydroxycortisol/cortisol ratio (a sign of CYP3A4 activity) increased from 7 to 13 in 13 people taking 900 mg/d for 14 days of an extract standardized to 0.3% hypericin Roby 2000
  Acute rejection in two heart transplant patients due to a metabolic interaction of St John's wort and cyclosporin. Plasma cyclosporin levels returned to normal after Hypericum was discontinued Ruschitzka 2000
  Synaptosome uptake inhibition by hyperforin of glutamate (Vmax 8.3 to 1.8 pmol) & GABA (Vmax 2.8 to 0.8 pmol). Effect is reduced by amiloride derivatives; mimiced but reduced by monesin or ouabain indicating role of Na+ channels Wonnemann 2000
  Cyclosporin A or bongkrekic acid, inhibitors of mitochondrial permeability, don't protect cells from hypericin-induced mitochondrial permeability. Bcl-2 delays hypericin induced caspase-3 activation Chaloupka 1999
  Review warns about interactions of Ginkgo with anticoagulants; St. John's wort with prescription antidepressants and effects on neurotransmitters; Ephedrine with cardiovascular events & seizures; Ginseng with warfarin Cupp 1999
  Increased plasma growth hormone, decreased plasma prolactin and unchanged plasma cortisol in 12 healthy volunteers taking 9 tablets of Jarsin 300 (2700 mg LI160) possibly indicating effect on brain dopamine Franklin 1999
  Reduction of animal models of depression by Hypericum is partially prevented by SCH 23390 (dopamine antagonist) or (-)-pindolol Gambarana 1999
  Digoxin plasma level area under the curve (AUC) was unaffected at day one but reduced 25% after 10 days of 900 mg/d Hypericum (LI160) in healthy volunteers. This might be due to P-glycoprotein induction Johne 1999
  Five cases of clinically diagnosed central serotonergic syndrome in elderly patients who combined prescription antidepressants with St. John's wort Lantz 1999
  Omeprazole, an inhibitor of H+K+-ATPase, and amiloride, an inhibitor of the Na+/H+ exchanger, potentiate the effect of hypericin (microM) on HL-60 cells Mirossay 1999
  Hypericin and pseudohypericin solubility are remarkably increased in the presence of a fraction containing procyanidins, especially procyanidin B2, which also significantly increased the in vivo effects Butterweck 1998
  Fagopyrum esculentum (buckwheat) contains red fluorescent compounds having photosensitizing properties and spectrum similar to hypericin, inhibits kinases, PKC, EGF-R & Ins-R at ng/ml Samel 1996
Contraindications
  Cyclosporin blood level fell 49% in 45 kidney & liver transplant patients taking St. John's Wort leading to rejection episodes in two patients Breidenbach 2000
  Patients on phenprocoumon or digoxin should not injudiciously discontinue St John's wort by themselves, as this could lead to toxic reactions of rebound in stabilised patients (comment on Ernst '99) De Smet 2000
  P450 induction by Hypericum must be kept in perspective with other unregulated inducers like cruciferous vegetables, alcohol, smoke and inhibition by grapefruit. Labelling with precautions is appropriate (comment on Ernst '99) Jobst 2000
  Pregnane X receptor, a regulator of P450 CYP3A4 monooxygenase expression in the nucleus, binds hyperforin (Ki=27 nM). Hepatocytes treated with hypericum extracts or hyperforin induced CYP3A4 expression Moore 2000
  7 warfarin patients with increased bleeding time and 8 women with intermenstrual bleeding possibly due to increased metabolism of oral contraceptives induced by St John's Wort (comment on Ernst '99) Yue 2000
  Review of the pharmacology, efficacy, safety, and pharmokinetics St. John's Wort, chromium, and garlic used for depression, diabetes, and hypercholesterolemia, respectively. Safety with renal patients is unstudied Duncan 1999
  Pharmacology, precautions, therapeutic uses, and adverse effects of ginkgo biloba, St. John's wort, saw palmetto, and soy reviewed Glisson 1999
  Hormonal effect raises concern about use by women and children Klepser 1999
  "Potential metabolic interaction between St. John's wort and theophylline " (no abstract) Nebel 1999
  A case of a woman switching from paroxetine (40 mg/d) to Hypericum (600 mg/d) for 10 days became lethargic after adding a 20 mg dose of paroxetine. She returned to normal the next day Gordon 1998
  "St John's wort during pregnancy " (no abstract) Grush 1998
  A measurable increease in erythema in light sensitive volunteers mainly after the highest dose, 600 mg 3 times daily for 15 days (11 mg hypericin). UV-A sensitivity increased from 10.8 J/cm2 to 8.7 J/cm2 Brockmoller 1997
EVIDENCE OF ACTIVITY
 
Animal Studies
  Hypericum perforatum extract (25-200 mg/kg) produced inhibitory effects on locomotor hyperactivity and reduced the number of stereotyped behaviors on ethanol withdrawal in male Wistar rats at second and sixth hour. Coskun 2006
  In Wistar rats, the effect of a treatment with high doses of SJW extract (100 and 1000 mg/kg/day) administered prenatally and during breastfeeding, on the level of transcripts of mdr1a, mdr1b, mrp1, mrp2 and cyp3A2 genes was investigated. Garrovo 2006
  The evaluation of the antioxidant effect of Hypericum perforatum in an experimental animal model of spinal cord injury, which was induced by the application of vascular clips to the dura via a four-level T5 through T8 laminectomy showed that it ameliorated the recovery of limb function. Genovese 2006
  Hypericum perforatum extract reduces the development of acute pancreatitis induced by cerulein administration in male CD mice. Genovese 2006a
  The combined treatment of bromocriptine (BRC) and Hypericum perforatum extract (HPE) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease in male Swiss Albino mice was more pronounced than BRC or HPE alone. Mohanasundari 2006
  Drugs that reliably decrease alcohol intake in the inbred Fawn-Hooded rats include 5-hydroxytryptamine-2A receptor antagonist, amperozide, the mGlu5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and herbal derivatives such as ibogaine, St. John's wort and kudzu extract. Overstreet 2006
  Hypericum perforatum extract found to attenuate the degree of zymosan-induced multiple organ dysfunction syndrome in mice. Paola 2006
  St John's wort extract and fluoxetine elevated brain and plasma corticosterone concentrations after subchronic treatment and St John's wort is the only antidepressant tested which slightly elevated P-glycoprotein level in the brain of mice. Weber 2006
  Hypericum perforatum exhibits antiedematogenic and antinociceptive properties in rats, which may be of value for the management of inflammatory painful conditions. Abdel-Salam 2005
  Fractionated administration of hypericin in C3H/DiSn mice found to produce a better antitumour effect than single administration. Cavarga 2005
  The ester derivative IDN 5491 (hyperforin-trimethoxybenzoate) showed antidepressant-like properties in the forced swimming test (FST) in rats, with no effect on open-field activity, when given as three intraperitoneal injections in 24 h at 3.125 and 6.25 mg/kg. Cervo 2005
  A 15-day oral treatment of male rats with Echinacea purpurea and Hypericum perforatum at the higher dose significantly inhibits prolactin production. Di Carlo 2005
  It is suggested based on studies conducted on rats that the antidepressant action of Hypericum perforatum is not mediated by a circadian mechanism. Francis 2005
  Aristoforin, a novel stable derivative of hyperforin, retains the antitumor properties of the parental compound without inducing toxicity in experimental animals. Gartner 2005
  Co-administered St. John's Wort (SJW) significantly ameliorated the toxicities induced by CPT-11 in rats and the protective effect of SJW is partially due to pharmacokinetic interaction between CPT-11 and SJW. Hu 2005
  Nelumbinis Semen provides greater anti-depression effects than Hypericum Perforatum in rats and the effects might be due to the modulation of the amount of neurotransmitters involved in depression. Kang 2005
  St. John's wort extract at 500 mg/kg in rats reduced prepulse inhibition response through enhancing monoaminergic transmission in brainstem, thalamus, cortex and/or hippocampus. Khalifa 2005
  The selective and pronounced effect of CO2 Hypericum perforatum extract, alone or combined with naltrexone, on ethanol intake in conditions of chronic treatment, without development of tolerance in rats was demonstrated. Perfumi 2005
  CO(2) Hypericum perforatum extract, markedly reduces the reinforcing properties of ethanol in the self-administration paradigm, as well as the increase of ethanol intake following ethanol deprivation in alcohol-preferring rats. Perfumi 2005a
  The effect of a Hypericum perforatum extract on the labeling of blood elements with technetium-99m and in the bioavailability of the radiopharmaceutical sodium pertechnetate in Wistar rats revealed its effect on erythrocytes and plasma and cellular proteins. [Article in Portuguese] Santos-Filho 2005
  It was observed that Hypericum perforatum prevented the deleterious effects of both chronic restraint stress and long-term corticosterone on learning and memory as measured in both, the object recognition and the water maze tests carried out with rats. Trofimiuk 2005
  The total flavonoids in St. John's Wort decreased activity of monoamine oxidase,inhibited ptosis & attenuation of autonomous behavior induced by reserpine respectively, and it was shown to inhibit behavioral despair & acquired helplessness & to prolong the sleep time in mice.[Article in Chinese] Xu 2005
  The hypocholesterolemic effects of a flavonoid-rich extract of St.John's Wort in Wistar rats might be due to its abilities to lower serum total cholesterol, total triglycerides, & LDL cholesterol levels as well as to slow the lipid peroxidation process & to enhance the antioxidant enzyme activity. Zou 2005
  The investigation of the antidepressant effect of Hypericum perforatum at doses 7, 35 and 70 mg kg(-1) b. m.) was described on mice using the forced-swimming and tail-suspension methods. Bach-Rojecky 2004
  The intraperitoneal administration of 30-100 mg/kg of St. John's Wort preparation in adult albino mice produced significant analgesic effect (75%) in acetic acid induced writhing and formalin licking tests. Bukhari 2004
  The two different commercially available Brazilian hydroalcoholic Hypericum perforatum extracts did not show the expected effects in a screening test for antidepressant agents, on the contrary, one of the extracts promoted a depressant-like effect in rats, in the forced swimming test. Guilhermano 2004
  In the rats treated with multiple administrations (15 mg/kg/d) of St. John's wort extract (SJW) for 2 weeks, the plasma concentration of nifedipine (NF) after oral administration was significantly decreased. Kobayashi 2004
  St. John's Wort given at a dose of 400 mg/kg/day in rats for 30 days induces hepatic multidrug resistance protein 2, glutathione S-transferase-P and cytochrome P450 1A2, overexpressions, and thus, it could affect drug metabolism, conjugation and disposition. Shibayama 2004
  Magnesium-depletion leads to enhanced depression- and anxiety-related behavior in mice and was further validated by the reversibility of the behavioral changes by desipramine and Hypericum perforatum extract. Singewald 2004
  Hypericum perforatum extract at 300 mg/kg, p.o, exerts an acute anxiolytic drug effect in mice on the marble-burying test, which could indicate a potential anti-obsessive effect, although the development of tolerance could be an important drawback. Skalisz 2004
  Evaluation of the effect of acute, subchronic (7 days), and chronic (21 days) Hypericum perforatum (150 and 300 mg/kg) extract administration in mice submitted to the mouse defense test battery, suggest anxiolytic-like and antipanic-like effects of H. perforatum extract. Beijamini 2003
  The putative antipanic/anxiolytic effect of standardised Hypericum perforatum extract (LI 160) on rats tested in the elevated T-maze, an animal model of innate (panic) and learned (generalised) anxiety, at doses that exhibit antidepressant-like activity was evaluated. Beijamini 2003a
  The roles of shade, fleece length and wool type in the protection of sheep from Hypericum perforatum poisoning was investigated and it was found that the ability of ruminant livestock to safely ingest Hypericum is determined by the amount of skin protection they have against incident sunlight. Bourke 2003
  It is shown that an St. John's wort extract (SJW) free of hyperforin and hypericin exerts antidepressant activity in behavioral models, and the flavonoids are part of the constituents responsible for the therapeutic efficacy of SJW extracts. Butterweck 2003a
  Investigation of the effects of an extract of Hypericum perforatum (Ph-50) on withdrawal signs produced by nicotine abstinence in mice reveals that treatment with Ph-50 attenuates nicotine withdrawal signs in mice. Catania 2003
  The review summarizes the findings of the effects on alcohol intake in alcohol-preferring rats of extracts or purified compounds from two of the most promising herbs: kudzu (Pueraria lobata) and St. John's Wort (Hypericum perforatum). Overstreet 2003
  It is found that Hypericum perforatum CO2 extract and opiate receptor antagonists act synergistically to induce a pronounced and selective reduction of voluntary ethanol consumption in alcohol-preferring rats. Perfumi 2003
  It is clear that pure compounds (daidzin, puerarin), extracts from St. John's wort, ibogaine and an ibogaine analog suppress alcohol intake in animal models of excessive drinking with minimal effects on other appetitive behaviors. Rezvani 2003
  Ethanol extracts of sect. Hypericum medicinal plants significantly shortened motionless time of mice forced swimming & espair time of mouse tail suspension in the two behavior despair animal models of depression. The effect of H. faberi was weaker than that of H. perforatum. [Article in Chinese] Wan 2003
  It is suggested that the effects of Hypericum perforatum extracts on alcohol drinking behaviour of alcohol-preferring rats are due to the hyperforin content of the herb rather than to other, more polar constituents. Wright 2003
  H. perforatum administered to mice for 4 days did not affect catalytic activities of CYP1A2, CYP2E1 and CYP3A and caused no significant change in the polypeptide levels. Bray 2002
  Low doses of hyperforin stimulate striatal ACh release by an unknown mechanism, whereas high doses inhibit synaptic choline uptake and ACh release in mice. Buchholzer 2002
  Long-term, but not short-term, administration to rats of Hypericum extract and hypericin modify levels of neurotransmitters in brain regions involved in the pathophysiology of depression. Butterweck 2002
  H. perforatum extract alone failed to offer neuroprotection to injured retinal ganglion cells but when mixed with Panax quinquefolius extract and Ginkgo biloba extract significantly augmented survival and regeneration. Cheung 2002
  In rats submitted to elevated T-maze, light/dark transition, and cat odor test, H. perforatum exerted anxiolytic-like effects in a specific subset of defensive behaviors, particularly those related to generalized anxiety. Flausino 2002
  The most polar constituents of crude ethanol extract of Hypericum perforatum exerted highest antiepileptic activity in Chinchilla rabbits. Lipid-soluble constituents in ether fraction potentated epileptic activity. Ivetic 2002
  Indian Hypericum perforatum treatment caused a significant decrease in the binding of [3H] spiroperone (DA-D2 receptor) to the striatum and increase in the binding of [3H] ketanserin (5-HT2A receptor) and [3H] flunitrazepam (BDZ receptor) to the frontal cortex in rats. Kumar 2002
  Addition of rutin to the inactive aqueous alcoholic extract of H. perforatum resulted in increased activity. Noldner 2002
  A CO2 Hypericum perforatum extract (HPE) given by intragastric injection, markedly reduces ethanol intake in msP rats & it is suggested that inhibitory effects of HPE on ethanol intake are not mediated by GABA agonist actions. Perfumi 2002
  Echinacea purpurea & Hypericum perforatum were evaluated for their anti-inflammatory activity against carrageenan-induced paw oedema in mice & found that anti-inflammatory effect of these extracts could be in part related to their modulation of COX-2 expression. Raso 2002
  It is found that antioxidants and herbal products like St. Johns wort and GS-02 could be useful in the treatment of chronic fatigue syndrome in mice. Singh 2002
  Co-administration of antioxidants carvedilol, melatonin, Withania somnifera, quercetin or St. John's wort significantly reduced lipid peroxidation and restored the GSH levels decreased by chronic swimming in mice. Singh 2002a
  It is found that the long-term administration of Hypericum perforatum in rats, can improve learning and spatial memory with significant changes in the content of monoamines in several brain regions. Widy-Tyszkiewicz 2002
  Hypericum and hypericin have delayed effects on HPA axis control centers similar to those of imipramine, and long-term treatment can prevent select stress-induced changes in gene transcription in particular brain areas. Butterweck 2001
  Imipramine, Hypericum extract and hypericin given daily for 2 weeks reduced immobility time in the FST, decreased plasma ACTH and corticosterone levels with no pronounced effects on plasma prolactin or LH levels. Butterweck 2001
  Pregnant rats treated with SJW showed no effects on maternal weight gain or duration of gestation, no behavioral alterations and no significant effects on whole and regional brain weights of offspring at adulthood. Cada 2001
  Administration of Hypericum extract to male interleukin-6 knock-out and wild type mice indicate that IL-6 could be necessary to the antidepressant action, and that this cytokine may mediate through activation of the serotonin system. Calapai 2001
  Hypericum extract enhanced serotonin, norepinephrine and dopamine content in the brain and reduced the immobility time of rats in the forced-swimming test. Further addition of Sulpiride, metergoline and 6-OH-DA increased immobility time. Calapai 2001
  Lyophilised aqueous extracts of H. perforatum, devoid of hyperforin, showed a clear sedative and anxiolytic effect of mice in the elevated plus maze, open-field, and horizontal-wire tests. Coleta 2001
  Systemic administration of 2 clinical preparations of H. perforatum were found to have no effect on discharge rate of serotonin-containing neurons in the dorsal raphe nucleus of awake cats. Fornal 2001
  2 mg/kg intravenous bolus dose of Hypericin in nonhuman primates maintained plasma concentrations equal to in vitro concentration required for growth inhibition of human glioma cell lines, with severe photosensitivity skin rash seen at the 5 mg/kg dose level. Fox 2001
  In the acute-escape deficit model in rats, hyperforin showed ten times the potency of total extract in protecting rats from sequelae of unavoidable stress and appears to be the most likely active component responsible for antidepressant activity. Gambarana 2001
  The facilitatory effect of Hypericum extract on retrieval memory in mice showed involvement of adrenergic and serotonergic 5-HT1A receptors. Khalifa 2001
  Hypericum extract improved learning ability, memory in rats and almost completely reversed scopolamine-induced amnesia in mice with pure hyperforin being a more potent antidementia agent than an antidepressant. Klusa 2001
  Extract of H. perforatum showed significant anti-inflammatory and analgesic activity and potentiated the anti-inflammatory activity of indomethacin and analgesic activities of pentazocine and aspirin. Kumar 2001
  Ethanolic extract of Indian Hypericum perforatum decreased serotonin and 5-hydroxy indole acetic acid levels, augmented levels of norepinephrine, methylhydroxy phenyl glycol, dopamine and dihydroxyphenyl acetic acid in rats. Kumar 2001
  Treatment with Hypericum extract improved resistance to stress and prevented exhausting of the hypothalamic-pituitary-adrenal system in rats. Makina 2001
  Hypericum may enhance 5-HT and noradrenaline transmission with high doses affecting neuronal 5-HT uptake mechanisms more like TCAs than SSRIs. Hyperforin may play a major role in the action of hypericum, both are active in the scopolamine test. Misane 2001
  Hyperforin conjugates exhibit significant antidepressant activity as evidenced by the reduced immobility period in the FST in rats. Muruganandam 2001
  H. perforatum extracts dose-dependently reduced ethanol intake in alcohol-preferring rats with Hyperforin showing importance. Mechanisms differ for reduction of ethanol intake and antidepressant-like effect. Perfumi 2001
  A review of in vivo experiments suggesting that hyperforin may be more beneficial than Hypericum extract in the treatment of depressive disorders. Philippu 2001
  Maternal administration of hypericum before and throughout gestation did not affect long-term growth and physical maturation of exposed mouse offspring. Rayburn 2001
  Prenatal exposure to a therapeutic dose of hypericum did not have a major impact on certain cognitive tasks in mice offspring. Rayburn 2001
  Methanolic Hypericum extract and hyperforin showed imipramine-like effect on mesolimbic, dopaminergic and serotonergic neurones in acute and chronic experiments in rats. Rommelspacher 2001
  Ingestion of H perforatum by sheep followed by exposure to bright sunlight frequently resulted in skin irritation and increase in body temperature in a dose dependent manner. Bourke 2000
  Dopamine release increased in the rat brain 80-100 min after H. perforatum-CO2 extract (1 mg/kg, p.o.) without affecting 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) Di Matteo 2000
  St John's Wort induces intestinal P-glycoprotein/MDR1 in rats and humans, hepatic CYP3A2 in rats, and intestinal and hepatic CYP3A4 in humans. Durr 2000
  Extracts of H. perforatum showed stimulatory and antidepressant effects on the CNS, prolonged sleep, reduced myorelaxant activity of diazepam, reduced abdominal stretching induced by acetic acid by nearly 50 %, and reduced intestine motility. Jakovljevic 2000
  Possible nootropic action in rats of ethanolic extract of Indian H. perforatum, which was qualitatively comparable with that induced by piracetam. Kumar 2000
  Sarcoid tumor volume in a donkey was reduced 81% by photodynamic therapy with 4 hypericin injections and illumination daily for 25 days Martens 2000
  Wound healing was improved by ointment containing H. hookerianum leaf methanol extract for rats Mukherjee 2000
  Wound contracting, wound closure time, regeneration of tissues & tensile strength of the wound improved over control with Hypericum patulum (5% w/w ointment of leaf methanol extract in ointment) in rats Mukherjee 2000
  Antidepressant-like effect of H. perforatum may be mediated by sigma receptors and to some extent by increased serotonergic neurotransmission, but these mechanisms appear to be unimportant for the effect on ethanol intake. Panocka 2000
  Antenatal exposure to Saint John's wort showed no long-term deficits on selected behavioral tasks by developing mice offspring. Rayburn 2000
  Activity increase & anxiolytic effect by H. perforatum extract in rats is blocked by Flumazenil (benzodiazepine antagonist). GABA-activated currents are reduced by hypericin & increased by pseudohypericin. NMDA receptors are blocked by both Vandenbogaerde 2000
  5-HIAA levels were increased in mouse brain 3 h after Hypericum extract @ 10 mg/Kg. Increased brain 5-HT and reduced plasma tryptophan was also observed Yu 2000
  Inhibition of formalin induced hindpaw licking and increased tail flick latencies of mice given Hypericum triquetrifolium @ 10, 25, 50 & 60 mg/kg Apaydin 1999
  Cortex 5-HT is increased by Hypericum (Li 160 or Ph-50) or fluoxetine in rats. Brainstem 5-HT is increased only by the latter two. Both Hypericum preparations increased diencephalon noradrenalin & dopamine Calapai 1999
  Rat depression & alcoholic models benefit from imipramine (3-30 mg/kg), fluoxetine (3-30 mg/kg) and hypericum extracts Ze 117 (Remotiv) & LI 160 (Jarsin), 5-40 mg/kg, i.p., triple application De Vry 1999
  Like Ro 04-1284 (reserpine analog) H. peforatum depletes nerve storage vesicles to raise cytoplasmic levels of 5-HT, rather than acting on receptors. 5-HT accumulation in synaptosomes is inhibited by hyperforin & H. perforatum, IC50=1.8 & 7.9 microg/ml Gobbi 1999
  Dopamine, noradrenaline, serotonin & glutamate are increased by hyperforin (10 mg/kg, i.p.) in rat locus coeruleus whereas 5-HIAA, GABA, taurine, aspartate, serine and arginine, were not influenced Kaehler 1999
  Antidepressant effects in rodent behavior tests by Hypericum perforatum (100 mg/kg) were comparable to imipramine (15 mg/kg) after 3 days Kumar 1999
  Alcohol consumption decreased in genetic alcohol-preferring rats by hypericin extract (0.3% hypericin) @ 250 mg/kg i.g. without affecting blood-alcohol levels. 500 mg/kg induced immobility & general suppression of ingestion Perfumi 1999
  Alcohol consumption decreased in 2 genetic animal models of alcoholism treated with Hypericum (100-800 mg/kg) Rezvani 1999
  Proliferative vitreoretinopathy (which depends on PKC) induced in rabbits was less severe in those getting an intravitreal injection of 10 or 100 muM hypericin Tahara 1999
  Iron chelation and scavenging of superoxide & hydroxyl radicals by H. perforatum shoot alcoholic extract Tripathi 1999
Pharmacodynamics
  Hyperforin, a polyprenylated acylphloroglucinol derivative from St. John's wort exhibits antidepressant activity, antibiotic activity and antitumoral activity in vivo. Beerhues 2006
  An in vitro model system consisting of human epidermoid carcinoma cells (A431) and hypericin as a photosensitizer was used to study the time- and dose-dependent characteristics of hypericin-photodynamic treatment-based induction of cytotoxicity and apoptotic cell death. Berlanda 2006
  It has been demonstrated that expression of p27(SJ), a novel protein in St John's Wort decreases the level of viral replication in HIV-1-infected cells. Darbinian-Sarkissian 2006
  The psychoactive herbal extracts from Hypericum, Passiflora and Valeriana, found to act on gamma-amino butyric acid and serotonin (5-HT) receptors, which are recognized targets of pharmacological antidepressant treatment. Gramowski 2006
  St John's wort extracts (SJWE) containing hyperforin induced significantly multidrug resistance gene 1mRNA expression, whereas no hepatic cytochrome P450 3A4 induction was observed after treatment with any of the investigated SJWE. Gutmann 2006
  Investigation among different St John's Wort commercial preparations available on the French market, which are used to treat depression showed that only one preparation gave significant results in the forced swimming test. Jean 2006
  The light-dependent tumor destructive properties of Hypericin, a naturally occurring secondary metabolite in Hypericum perforatum, have drawn attention to its promising application as a photosensitizer in the frame of Photodynamic Therapy. Kiesslich 2006
  Hyperforin, a constituent of St. John's wort, was found to inhibit the N-methyl-D-aspartate (NMDA)-induced calcium influx into cortical neurons and it exhibited potential neuroprotective effects in vitro. Kumar 2006
  Hyperforin is a lipophilic compound that is present in great amounts in St. John's wort has been attributed for the antidepressant effects of this medicinal plant and it has effects on inflammation, as well as antibacterial, antitumoral and antiangiogenic effects. Medina 2006
  It has been indicated that prevention of nuclear factor-kappaB and signal transducer and activator transcription-3 activation by Hypericum perforatum extract reduces the development of acute inflammation. Menegazzi 2006
  It has been suggested that hypericin derivatives may serve as powerful necrosis-avid diagnostic agents for assessment of tissue viability. Ni 2006
  Hyperforin isolated from St John's wort, promotes apoptosis of various cancer cells from solid tumors & hematological malignancies, including B-cell chronic lymphocytic leukemia & it inhibits the capacity of migration & invasion of different tumor cells, as well as exhibiting antiangiogenic effects. Quiney 2006
  The effects of the hyperforin, a natural phloroglucinol purified from Hypericum perforatum, were investigated ex vivo on leukemic cells from patients with B-cell chronic lymphocytic leukemia. Quiney 2006
  Upon light emission the naphthodianthrone derivatives (in 1.37% w/w), and chlorophylls (in 0.08% w/w) of Hypericum perforatum can be activated, and making them a potent, natural photosensitizers for use in photodynamic therapy, and photodynamic diagnosis. Skalkos 2006
  The polar methanolic fraction of the Hypericum perforatum L. extract has recently been developed and tested as a novel, natural photosensitizer for use in the photodynamic therapy, and photodynamic diagnosis. Stavropoulos 2006
  [St. John's Wort and its Active Principles in Depression and Anxiety.] Szabadi 2006
  Essential oils extracted from 24 different plants including Foeniculum vulgare L., and Hypericum perforatum L., were screened in guinea pig and rat plasma in order to assess antiplatelet activity and inhibition of clot retraction. Tognolini 2006
  It is found that Hypericum perforatum prevents stress-induced deterioration of memory in rats. Trofimiuk 2006
  Hypericum perforatum was found to protect the rat pulmonary microvascular endothelial cells from acute injury induced by paraquat. [Article in Chinese] Wei 2006
  The in vitro photoactivity of Hypericin-loaded polymeric nanoparticles was investigated on the NuTu-19 ovarian cancer cell model derived from Fischer 344 rats and compared to free drug. Zeisser-Labouebe 2006
  Study of the mechanism of development of neurological disorders in AIDS patients showed that St. John's Wort contains a protein that inhibits HIV-1 replication. [No authors listed] 2005
  Testosterone hydroxylase activity and Western blots indicate that St. John's Wort did not activate detoxication pathways in a similar manner to 4-Nonylphenol. Baldwin 2005
  The evaluation of St John's wort on contractions induced by electrical field stimulation or exogenous agonists in isolated rat and human vas deferens demonstrate that SJW directly inhibits rat and human vas deferens contractility. Capasso 2005
  Traditionally St. John's Wort, is used as a natural treatment for depression & it activates a nuclear receptor called pregnane X receptor which is a ligand-activated transcription factor that induces a number of xenobiotic-metabolizing enzymes including cytochrome P4503A4 (CYP3A4) in humans. Choudhuri 2005
  Hypericum perforatum extract exerts multiple protective effects in splanchnic artery occlusion-reperfusion shock in rats and it may be a candidate for consideration as a therapeutic intervention for ischemia-reperfusion injury. De Paola 2005
  Green tea extract, St. John's Wort extract and epigallocatechin-3-gallate exhibit a specific and strong anti-signal transducers and activators of transcription 1 activity which is independent of their acclaimed strong anti-oxidant activity. de Prati 2005
  [St. John's wort treatment relieves skin inflammation and pruritus in neurodermatitis][Article in German] Deutsches Grunes Kreuz e 2005
  St. John's wort administration resulted in a significant induction of CYP2D2 and CYP3A2, and in a significant inhibition of CYP2C6 metabolic activities in perfused rat liver. Dostalek 2005
  The efficacies of naturally occurring analogues of hyperforin, isolated from H. perforatum and its synthetic derivatives were evaluated in intact human polymorphonuclear leukocytes and the inhibitory effects on isolated recombinant human 5-LO were investigated. Feisst 2005
  The spasmolytic effects of Hypericum perforatum are mediated through dual inhibition of calcium influx and phosphodiesterase (PDE)-like mechanisms, which might explain the medicinal use of St John's wort in the disorders of gastrointestinal and respiratory tracts. Gilani 2005
  The extracts of Hypericum perforatum aerial parts contribute to the control of petit mal seizure and the effect may be partially mediated by nitric oxide pathway. Hosseinzadeh 2005
  Serotonin transporters are high affinity targets in vivo for antidepressants such as serotonin selective reuptake inhibitors which include 'medical' psychopharmacological agents such as analgesics and antihistamines, a plant extract called St John's Wort (Hypericum). Ito 2005
  Among 21 plants used in Bulgarian phytotherapy, seven plants including Hypericum perforatum (TEAC 3.75+/-0.14 mM/QE 881.93+/-6.68 microM), were with high phenolics content and antioxidant properties. Ivanova 2005
  Using an in-vivo microdialysis technique, the serotonin-enhancing effect of Nelumbinis Semen on rat hippocampus was investigated and its effects compared with those of two well-known antidepressants, Hypericum perforatum (St John's wort) and fluoxetine. Kang 2005
  Photodynamic treatment with both polar methanolic fraction of Hypericum perforatum & methanolic extract induces the killing of HL-60 leukemic cells and the optimal conditions of treatment were determined. Kapsokalyvas 2005
  Recent studies report antidepressive, antineoplastic, antitumor and antiviral (human immunodeficiency and hepatitis C virus) activities of hypericin. Kubin 2005
  It is shown that hyperforin inhibits angiogenesis in vitro in bovine aortic endothelial cells and in vivo in the chorioallantoic membrane assay. Martinez-Poveda 2005
  The effect of three herb extracts, Hypericum perforatum, Ginkgo biloba L. and Apocynum venetum L., and their components on lipid hydroperoxide-induced oxidative stress in PC-12 cells have been examined. Shirai 2005
  Herbal extracts valerian and St. John's wort were studied for their metabolic changes upon incubation with freshly prepared rat hepatocytes and subsequently analysed phytochemically as well as pharmacologically in vitro. Simmen 2005
  The cytotoxic activity of the locally collected (Epirus region) Hypericum perforatum L. against cultured T24 and NBT-II bladder cancer cell lines have been investigated. Skalkos 2005
  Time-resolved microspectrofluorimetry & fluorescence lifetime imaging were used to assess spectral & temporal properties as well as spatial distribution of fluorescence emitted by retinal pigment epithelium (RPE) cells treated with Hypericin at at 0.5-10 microM. Taroni 2005
  The screening for antioxidative compounds for topical administration resulted in new, interesting findings. Thus the Buckwheat extract significantly reduced the level of irradiation induced lipid peroxidation as well as the extracts of St. John's Wort, melissa and sage. Trommer 2005
  [St John's Wort improves somatoform disorders.] Werneke 2005
  [Versatile St. John's wort] [Article in German] [No authors listed] 2004
  The main constituents of hypericum extract, determined by HPLC analysis, were flavonoids, hypericins & hyperforins. Incubation of selected microorganisms with pure chemicals resulted in a significant inhibition of their growth by hypericin, hyperforin & its stable dicyclohexilammonium salt. Avato 2004
  Standardized extract of Hypericum perforatum shows relevant antioxidant activity both in vitro and in a cell system, by means of inhibiting free radical generation and lipid peroxidation. Benedi 2004
  It is suggested that besides hypericin, flavonoids of St John's Wort play an important role in the modulation of hypothalamic-pituitary-adrenal axis function. Butterweck 2004
  It is demonstrated that St. John's wort inhibits excitatory transmission of the rat urinary bladder and also directly inhibits smooth muscle contractility. Capasso 2004
  The effects of the feverfew, ginkgo biloba, garlic, ginseng, and ginger, valerian, kava, St. John's wort, ephedra (Ma huang or metabolite), and Echinacea were reviewed. Ciocon 2004
  The in vitro metabolism profile of hyperforin was investigated using liver microsomes from male and female Sprague-Dawley rats, with or without induction by phenobarbital or dexamethasone. Cui 2004
  Hyperforin, the major lipophilic constituent of St. John's wort, was assayed as a stable dicyclohexylammonium salt was found to be an interesting lead compound to prevent and contrast cancer spread and metastatic growth. Dona 2004
  The effects of St. John's wort (SJW) extract and of hyperforin was tested on the properties of murine brain membrane fluidity and the oral administration of SJW extract and of hyperforin sodium salt results in significant hyperforin brain levels. Eckert 2004
  It is found that hyperforin inhibited the generation of reactive oxygen species and the release of leukocyte elastase in human isolated polymorphonuclear leukocytes, challenged by the G protein-coupled receptor ligand N-formyl-methionyl-leucyl-phenylalanine. Feisst 2004
  The effect of sub-chronic treatment with an extract of Hypericum perforatum (LI 160) on brain levels of corticosterone and cortisol in the rats was investigated. Franklin 2004
  Hyperforin-and its dicyclohexylammonium salt inhibited, the IL6 release induced in U373MG cells by two other classic proinflammatory stimuli,ILl and lipopolysaccharide (LPS), as well as the LPS-induced IL6 release in whole rat blood. Gobbi 2004
  [St John's wort, depression, and catecholamines.] Haller 2004
  St John's wort inhibited brain synaptosomal [(3)H]serotonin uptake in mice with little effect on specific [(3)H]paroxetine binding. Hirano 2004
  St. John's Wort has potent vasodepressor activity in the pulmonary vascular bed of the cat and the response is mediated or modulated by both a calcium channel and GABA receptor sensitive pathway. Hoover 2004
  Hypericin is a photosensitizer with a potent photocytotoxicity and it could be used for whole bladder wall photodynamic therapy of superficial bladder tumors. Kamuhabwa 2004
  Hyperforin, the major active constituent of St John's wort extract, increases the release of acetylcholine from rat hippocampus in vivo as determined by microdialysis. Kiewert 2004
  It is indicated that ascorbate transport per se is not altered during photodynamic therapy and vitamin C does not interfere with hypericin-induced photodamage of cellular targets. Laggner 2004
  A possible antioxidant role for the ligandin activity of glutathione S-transferase and a striking example of protein-specific effects on hypericin photodynamic activity was demonstrated for the first time. Lu 2004
  The standard extracts of Hypericum perforatum exhibited upgrading and significant protective effects on the trauma of PC12 cells induced by 200 microM H2O2. Lu 2004a
  The inhibitory effects of six flavonoids from Hypericum perforatum were assessed spectrophotometrically using nitric oxide synthase (NOS) in blood and cerebral homogenate of rats. Luo 2004
  A significant reduction of tumor growth and number of metastasis suggesting that Hypericum perforatum methanolic extract may be useful in the treatment of prostate cancer. Martarelli 2004
  P-glycoprotein expression in brain or liver was not induced by any treatment as determined by Western blot, whereas dexamethasone, pregnenolone-16alpha-carbonitrile (PCN), St. John's wort (SJW), and rifampin induced hepatic CYP3A expression. Matheny 2004
  To clarify implications of herbal alternative medicine use during electroconvulsive therapy, 5 herbal medicines including ginseng, Ginkgo biloba, St. John's wort, in combination with the terms "drug interaction," "adverse effects," "side effects," "safety," & "toxicity was studied. Patra 2004
  Comparative testing of the influence of Hypericum perforatum and of purified hypericin on the growth of a human erythroleukemic cell line (K562) confirms the role of Hypericum perforatum in cancer therapy. Roscetti 2004
  Hyperforin-induced efflux of [3H]5HT and [3H]DA reflect elevated cytoplasmic concentrations of the two monoamines secondary to the depletion of the synaptic vesicle content and the compartmental redistribution of nerve ending monoamines. Roz 2004
  [Antidepressive therapy does more than lighten mood. St John's wort helps the patient get through the daily grind.] [Article in German] Rudolf 2004
  It is confirmed that the potency of St John's wort products in inhibiting the uptake of serotonin depends on the amount of hyperforin in their dosage forms. Schulte-Lobbert 2004
  The neuroprotective role of a Hypericum perforatum ethanolic extract was assessed and fractions in amyloid-beta peptide (Abeta)((25-35))-induced cell death in rat cultured hippocampal neurons. Silva 2004
  Short-term (2 wks) treatment with methanolic St. John's wort extract decreased beta-adrenergic receptor (AR)-binding (14%), & no effects for this extract were observed after 8 weeks, but treatment with hypericin led to a significant down-regulation of beta-AR's in rat frontal cortex after 8-weeks.