St. John’s Wort Monograph

Scientific name of St. John's Wort:
Hypericum perforatum

Action of St. John's Wort:
Supports a healthy neurotransmitter balance

St. John's Wort is used for these common wellness concerns:
Depressed mood and mild to moderate mood changes caused by everyday stress; occasional nervousness, nervous tension, and anxiety

Find St. John’s Wort in these Clarocet blends:

An Overview of St. John’s Wort

St. John’s Wort is an aromatic perennial herb with an abundance of golden-yellow flowers. Tiny perforations filled with phytochemical-rich oils cover the aerial (above- ground) portions of St. John’s Wort and yield an extract that gives the plant its primary health benefits.

Current usage statistics indicate that millions of Americans supplement their daily diets with St. John’s Wort to promote positive mood balance. In the United States and Europe, St. John’s Wort is primarily used to provide positive support for:

  • Depressed mood and mild to moderate mood changes caused by everyday stress
  • Occasional nervousness, nervous tension and anxiety

The medicinal components of St. John’s Wort, which include Hypericin and Hyperforin, have been clinically shown to promote a healthy neurotransmitter balance, which can help to provide positive mood support following two to six weeks of continued use.

Science and Pharmacology of St. John’s Wort

Contemporary research has identified a variety of medicinal compounds from the portions of the St. John’s Wort plant that grow above the ground. There are at least 10 phytochemical constituents thought to contribute to the plant’s natural neurotransmitter reuptake inhibition, its primary mechanism of action. These components include:

  • Ad-hyperforin
  • Dianthrone
  • Hyperforin
  • Hypericin
  • Xanthones
  • Flavonoids

Modern extracts of St. John’s Wort are typically standardized to 0.3 percent Hypericin, because it is this compound which is thought to be more stable than its counterpart, Hyperforin. Recent scientific research indicates that Hyperforin extract, whether it is standardized to three percent, five percent or 10 percent, is highly unstable. Upon chemical analysis, St. John’s Wort extracts containing Hyperforin derivatives showed evidence of rapid breakdown. Further study concluded that regardless of the particular standardization amount, Hyperforin extracts decreased to their naturally occurring level of three to four percent concentration or less in all cases.

Until recently it was believed that Hyperforin was primarily responsible for the emotional health benefits of St. John’s Wort. However, further laboratory analysis has revealed that all the chemical components of St. John’s Wort are required in order to maximize the effects of its natural reuptake inhibition in the central nervous system.

Research shows that Hypericin, Flavonoids and Adhyperforin, other important constituents derived from St. John’s Wort, are also potent reuptake inhibitors of Serotonin, Dopamine and Noradrenalin. Additionally, St. John’s Wort has been demonstrated to inhibit GABA and L-Glutamate uptake. Together, these compounds are believed to promote healthy neurotransmitter balance in the brain. This effect is thought to provide positive support for depressed mood and mild to moderate mood changes caused by everyday stress, occasional nervousness, nervous tension and anxiety.

St. John’s Wort Safety and Usage

St. John’s Wort maintains an excellent safety profile when it is used as directed. A dose of 200 to 600 milligrams taken for two to six weeks is recommended to promote healthy neurotransmitter balance. In certain instances, individuals may increase their daily intake of St. John’s Wort to as much as 1200 milligrams to relieve depressed mood and mild to moderate mood changes caused by everyday stress, as well as occasional nervousness, nervous tension and anxiety.

What are the potential side effects of St. John’s Wort?

Side effects are rare and have been documented as mild to moderate in clinical study. They may include headache, gastrointestinal discomfort, drowsiness, dizziness and sensitivity to UV light sources. In the event that you experience an adverse reaction, discontinue use of this herb. St. John’s Wort does not cause withdrawal or discontinuation effects.

Is St. John’s Wort safe for children?

St. John’s Wort is generally well-tolerated when used by children between the ages of seven and 13. Because each child is unique, St. John’s Wort should be administered under the supervision of a professional healthcare provider.

Does St. John’s Wort adversely interact with prescription drugs?

Taking St. John’s Wort in combination with prescription medications such as benzodiazepines, SSRIs (selective serotonin reuptake inhibitors), or SNRIs (serotonin-norepinephrine reuptake inhibitors) may cause drowsiness. St. John’s Wort is also believed to decrease the effectiveness of certain prescription drugs, including oral contraceptives and medications used to treat high blood pressure. If you are taking a prescription medication, it is recommended that you consult with your prescribing doctor before making any changes or additions to your current treatment plan.

What precautions should I take before beginning St. John’s Wort?

Consult with your healthcare provider before beginning a wellness plan that includes dietary supplements like St. John’s Wort.

  • Do not take St. John’s Wort if you are pregnant or nursing
  • Do not take St. John’s Wort if you are currently taking a prescription MAOI
  • Do not take St. John’s Wort if you are currently taking a protease inhibitor for HIV/AIDS
  • Do not operate vehicles or heavy machinery until you know how St. John’s Wort affects you

St. John’s Wort Clinical Studies

Clinical Study Meta-Analysis and Peer Reviews

1. Dietary Supplements and Natural Products as Psychotherapeutic Agents
Adriane Fugh-Berman, MD and Jerry M. Cott, PhD
From the Department of Health Care Sciences (A.F.-B.), George Washington University School of Medicine and Health Sciences, Washington, DC; and Adult Psychopharmacology Program, National Institute of Mental Health, MD.
[Read the Abstract] [Read the Full Text ]

Excerpt From This Meta-Analysis:
"Many studies have been performed on this herb in Europe, primarily Germany. A recent meta-analysis evaluated 23 randomized trials (20 were double blind) of SJW in a total of 1757 outpatients with mild to moderate depression. Improvement in depressive symptoms (usually measured by the HAM-D or Clinical Global Impression scale) was observed in all groups. In 15 placebo-controlled trials, SJW was found to be significantly more effective than placebo. In eight treatment-controlled trials, clinical improvement in those receiving SJW did not differ significantly from those receiving tricyclic antidepressants."

2. Clinical trials with hypericum extracts in patients with depression--results, comparisons, conclusions for therapy with antidepressant drugs.
Phytomedicine. 2002 Jul;9(5):468-74. PMID: 12222670
[Read the Abstract]

Excerpt From This Meta-Analysis:
"Results from 34 controlled, double-blind trials of Hypericum extracts in some 3000 patients, predominantly with mild to moderate forms of depression, had been published. An overview is given of the studies conducted since 1990. In the majority of them, the efficacy criterion (primary endpoint) was the score and/or response rate on the Hamilton Rating Scale of Depression (HAMD). In ten studies the dosages ranged from 300 mg to 1050 mg of extract per day. Five of the ten studies were placebo-controlled and in all five cases, the Hypericum extract was shown to be significantly superior."

3. St John's wort for depression--an overview and meta-analysis of randomised clinical trials.
Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D.
Projekt Munchener Modell, Ludwig-Maximilians-Universitat, Munich, Germany.
BMJ. 1996 Aug 3;313(7052):253-8. PMID: 8704532
[Read the Full Text]

Objective: To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs.
Design: Systematic review and meta-analysis of trials revealed by searches.
Trials: 23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment.
Main outcome measures: A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects.
Results: Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants.
Conclusion: There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders.

4. Cluster analysis of symptoms during antidepressant treatment with Hypericum extract in mildly to moderately depressed out-patients. A meta-analysis of data from three randomized, placebo-controlled trials.
Kasper S, Dienel A.
Department of General Psychiatry, University of Vienna, Vienna, Austria
Psychopharmacology (Berl). 2002 Nov;164(3):301-8. Epub 2002 Sep 14 PMID: 12424554 [Read the Abstract]

Clinical Trials and Laboratory Tests

1. Hyperforin as a possible antidepressant component of hypericum extracts.
Chatterjee SS, Bhattacharya SK, Wonnemann M, Singer A, Muller WE.
Pharmacology Department, Dr. Willmar Schwabe GmbH & Co., Karlsruhe, Germany.
Life Sci. 1998;63(6):499-510. PMID: 9718074 [Read the Abstract]

2. In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract.
Cott JM
Pharmacologic Treatment Research Program, National Institute of Mental Health (NIMH), National Institutes of Health, Maryland, USA
Pharmacopsychiatry. 1997 Sep;30 Suppl 2:108-12. PMID: 9342770 [Read the Abstract]

3. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression.
Behnke K, Jensen GS, Graubaum HJ, Gruenwald J.
PhytoPharm Consulting, Institute for Phytopharmaceuticals, Berlin, Germany.
Adv Ther. 2002 Jan-Feb;19(1):43-52. PMID: 12008860 [Read the Abstract]

4. Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study.
Brenner R, Azbel V, Madhusoodanan S, Pawlowska M.
St. John's Episcopal Hospital, Far Rockaway, New York 11691, USA.
Clin Ther. 2000 Apr;22(4):411-9. PMID: 10823363 [Read the Abstract]

5. Pharmaceutical quality of hypericum extracts.
Wagner H, Bladt S.
Institut fur Pharmazeutische Biologie der Universitat Munchen, Germany.
J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S65-8. PMID: 7857515 [Read the Abstract]

6. Step by step removal of hyperforin and hypericin: activity profile of different Hypericum preparations in behavioral models.
Butterweck V, Christoffel V, Nahrstedt A, Petereit F, Spengler B, Winterhoff H.
Institute of Pharmacology and Toxicology, Universitatsklinikum Muenster,Germany.
Life Sci. 2003 Jun 20;73(5):627-39. PMID: 12770617 [Read the Abstract]

7. Hyperforin--antidepressant activity by a novel mechanism of action.
Muller WE, Singer A, Wonnemann M.
Department of Pharmacology, University of Frankfurt, Frankfurt/M., Germany.
Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S98-102. PMID: 11518085 [Read the Abstract]

8. Adhyperforin as a contributor to the effect of Hypericum p. L. in biochemical models of antidepressant activity.
Jensen AG, Hansen SH, Nielsen EO.
The Royal Danish School of Pharmacy, Department of Analytical and Pharmaceutical Chemistry, Copenhagen.
Life Sci. 2001 Feb 23;68(14):1593-605. PMID: 11263672 [Read the Abstract]

9. Inhibition of substance P-induced cytokine synthesis by St. John's wort extracts.
Fiebich BL, Hollig A, Lieb K.
Department of Psychiatry, University of Freiburg Medical School
Pharmacopsychiatry. 2001 Jul;34 Suppl 1:S26-8. PMID: 11518071 [Read the Abstract]

10. Effects of hypericum extract on the expression of serotonin receptors.
Muller WE, Rossol R.
Institut fur Physiologische Chemie der Johannes-Gutenberg-Universitat, Mainz, Germany.
Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S63-4. PMID: 7857514 [Read the Abstract]

11. Incidence and clinical relevance of the interactions and side effects of Hypericum preparations.
Schulz V.
Phytomedicine. 2001 Mar;8(2):152-60. PMID: 11315759 [Read the Abstract]

12. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.).
Ernst E, Rand JI, Barnes J, Stevinson C.
Department of Complementary Medicine, Postgraduate Medical School, University of Exeter
Eur J Clin Pharmacol. 1998 Oct;54(8):589-94. PMID: 9860144 [Read the Abstract]

13. Selected Physical and Chemical Properties of Commercial Hypericum perforatum Extracts Relevant for Formulated Product Quality and Performance
Susan H. Kopleman, Agnes NguyenPho, William S. Zito, Fran X. Muller, and Larry L. Augsburger
University of Maryland, Department of Pharmaceutical Sciences, Food and Drug Administration, Department of Product Quality Research, Saint John's University, Department of Pharmaceutical Sciences, GlaxoSmithKline, Pharmaceutical Development
AAPS PharmSci. 2001; 3 (4): article 26. DOI: 10.1208/ps030426 [Read the Full Text]

14. Mechanism of action of St John's wort in depression : what is known?
Butterweck V.
Institute of Pharmacology and Toxicology, Universitatsklinikum Munster
CNS Drugs. 2003;17(8):539-62. PMID: 12775192 [Read the Abstract]

15. Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10.
Vorbach EU, Arnoldt KH, Hubner WD.
Department of Psychiatry and Psychotherapy, Ev. Krankenhaus Elisabethenstift, Germany.
Pharmacopsychiatry. 1997 Sep;30 Suppl 2:81-5 PMID: 9342765 [Read the Abstract]

16. No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract.
Arold G, Donath F, Maurer A, Diefenbach K, Bauer S, Henneicke-von Zepelin HH, Friede M, Roots I.
Institute of Clinical Pharmacology, University Medical Center Charite, Humboldt University, Berlin, Germany.
Planta Med. 2005 Apr;71(4):331-7 PMID: 15856409 [Read the Abstract]

17. The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's wort (Hypericum perforatum L.) for premenstrual symptoms.
Hicks SM, Walker AF, Gallagher J, Middleton RW, Wright J.
Hugh Sinclair Unit of Human Nutrition, The School of Food Biosciences, The University of Reading, UK.
J Altern Complement Med. 2004 Dec;10(6):925-32 PMID: 15673985  [Read the Abstract]

18. Treatment of somatoform disorders with St. John's wort: a randomized, double-blind and placebo-controlled trial.
Muller T, Mannel M, Murck H, Rahlfs VW.
Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum, Germany.
Evid Based Ment Health. 2005 Feb;8(1):13. PMID: 15272100  [Read the Abstract]

19. St John's wort or sertraline? Randomized controlled trial in primary care.
van Gurp G, Meterissian GB, Haiek LN, McCusker J, Bellavance F.
Emergency Department, St Mary's Hospital Centre, Montreal, QC.
Can Fam Physician. 2002 May;48:905-12 PMID: 12053635 [Read the Abstract]

20. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine.
Szegedi A, Kohnen R, Dienel A, Kieser M.
Charite-Universitatsmedizin Berlin, Campus Benjamin Franklin, Department of Psychiatry and Psychotherapy, Berlin, Germany.
BMJ. 2005 Mar 5;330(7490):503. PMID: 15708844 [Read the Abstract]

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Last Updated: February 2015 [PHMF-03-0]