St. John’s wort (Hypericum perforatum), also called Klamath weed, is a five-petaled yellow flower, which is especially plentiful in Northern California and Southern Oregon. The “St. John’s” name comes from the red color of the extract (from squeezed buds and flowers), which was associated with the blood of St. John the Baptist and the fact that the herb typically flowers around the time of the feast of St. John. St. John’s wort has been used for centuries for everything from a “protector against evil spirits” (depression) and for wound healing to its most common present-day use as an antidepressant. The active ingredients in St. John’s wort extract are unknown, but extracts standardized to contain napthodianthrone compounds such as hypericin and pseudohypericin along with phloroglucinols such as hyperforin and adhyperforin are known to be effective in alleviating mild to moderate depressive symptoms.
As an antidepressant, St. John’s wort has been shown to inhibit an enzyme (catechol-O-methyltransferase) which degrades certain neurotransmitters such as dopamine. It has also been shown to inhibit serotonin re-uptake in the brain, and to reduce expression of interleukin-6 and gamma-amino butyric acid (GABA) uptake. Each of these actions can contribute to alleviating depression by slowing the recycling of neurotransmitters needed for maintaining emotional balance. As an anti-viral agent, St. John’s wort has been reputed to inhibit replication of several viruses, including the Herpes simplex, HIV, and the virus that causes mononucleosis, but its use as a dietary supplement for treating viral infections is generally not supported.
St. John's wort appears to be helpful in about 50-60% of cases of mild to moderate depression – but as with prescription antidepressants, the full effect takes about 4-6 weeks to develop. It is important to note that St. John's wort should never be used for the treatment of severe depression (feelings of suicide, extreme inability to cope with daily life, severe anxiety, or extreme fatigue) – and physician-directed drug therapy may mean the difference between life and death.
That said, St. John’s wort is sold in a variety of forms, including tea, drops, tablets, and capsules. In tablet or capsule form, standardized St. John’s wort extracts, (300-900mg/day) represent a relatively safe and effective dietary supplement for those with mild to moderate depression, anxiety, or seasonal affective disorder.
Several clinical studies have been conducted to determine the efficacy of St. John’s wort for those with mild to moderate depression. In one review of 23 randomized trials (15 placebo-controlled and 8 drug comparisons) including nearly 2,000 patients with mild or moderate depressive disorders, extracts of St. John’s wort were nearly 3 times more effective than placebo, and were comparable to prescription anti-depressants and with fewer side effects (Gaster & Holroyd 2000). Across the studies, fewer than 1% of those taking St. John’s wort dropped out of the study, compared with a drop-out rate of 3% taking a prescription anti-depressant. Perhaps the most encouraging results were that in contrast to the high percentage of side effects in those taking prescription anti-depressants (52.8%), only 19.8% of those taking St. John’s wort experienced any adverse effects (Linde et al. 1996). Other well-controlled studies comparing the St. John’s wort extract LI 160 (from Lichtwer Pharma) to prescription anti-depressants such as Prozac (fluoxetine), sertraline (Zoloft), paroxetine (Paxil), imipramine, amitriptyline and maprotiline have all found St. John’s wort to be comparable in effectiveness, but superior to prescription drugs with regard to tolerability. Overall, more than a dozen double-blind placebo-controlled studies have been conducted (mostly small studies) with the majority supporting the case for the effectiveness of St. John's wort in alleviating mild to moderate depression (Hansgen et al. 1994; Harrer et al. 1994; Philipp et al. 1999.
In the one recent study in the literature that explored the use of St. John’s wort as a retroviral agent for use in HIV-infected patients (Woelk et al. 1994), over half of the patients discontinued treatment early because of severe cutaneous phototoxicity (skin sensitivity to sunlight exposure). Of those who remained in the study, there were no significant changes in virologic markers. It should be noted that HIV-positive patients should NOT use St. John’s wort without specific advise and consultation of their personal physician, as the herb has been shown to almost completely inactivate the effects of certain antiviral medications (indinavir and other protease inhibitors).
St. John’s wort is quite safe in terms of observed side effects, the most common of which are typically mild gastrointestinal upset, mild allergic reactions (skin rash), tiredness and insomnia/restlessness. There have been no published reports of serious adverse side effects from taking the herb alone and animal studies with large doses of St. John’s wort have not shown any serious problems. The most commonly studied adverse effect of St. John’s wort is its ability to cause photosensitivity, especially in fair-skinned individuals. This condition is reversible upon discontinuation of the herb. Thus, special care should be taken to avoid ultraviolet light, or to frequently apply sunscreen and wear sunglasses (due to an increased risk of cataracts) when it is necessary to be outside. Other side effects include gastrointestinal symptoms, dizziness, confusion and tiredness, and tend to be equivalent in incidence to placebo.
Scientific studies conducted in vitro (test tube studies) have shown St. John’s wort to be mutagenic and toxic to sperm, suggesting that it should not be taken when trying to become pregnant. On the other hand, St. John’s wort has also been shown to interfere with the action of certain oral contraceptives (birth control pills). St. John’s wort is not recommended for children, or for women who are pregnant or lactating.
Although direct side effects from consuming St. John’s wort appear to be quite rare, several recent reports have raised the possibility that the herb may interact with and decrease the effectiveness of various medications, including HIV drugs (protease inhibitors), immunosuppressants (such as cyclosporin for organ transplants), digoxin (for congestive heart failure), blood thinners (Coumadin/warfarin), chemotherapy drugs, (olanzapine/clozapine) and asthma medications (theophylline). If you are currently taking any of these, or other prescription medications, DO NOT begin taking OR discontinue taking St. John’s wort without first consulting your personal physician (abrupt withdrawal of the herb could increase blood levels of various medications, which could be dangerous in certain cases).
The recommended dosage for St. John’s wort is 900mg per day (300mg taken 3 times per day) of an extract of the flowers and leaves standardized to contain 0.3% hypericin in a complex of other natural compounds, or 3-5% hyperforin (the main constituent which is thought to inhibit neurotransmitter re-uptake). Minimal treatment time is 4-6 weeks. St. John’s wort is sold in the U.S. only as an herbal supplement, although it is marketed as a drug in Germany for the treatment of mild depression and anxiety.
1.Cott JM, Fugh-Berman A. Is St. John's wort (Hypericum perforatum) an effective antidepressant? J Nerv Ment Dis. 1998 Aug;186(8):500-1.
2.Firenzuoli F, Luigi G. Safety of Hypericum perforatum. J Altern Complement Med. 1999 Oct;5(5):397-8
3.Fugh-Berman A, Cott JM. Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med. 1999 Sep-Oct;61(5):712-28.
4.Gaster B, Holroyd J. St John's wort for depression: a systematic review. Arch Intern Med. 2000 Jan 24;160(2):152-6.
5.Hansgen KD, Vesper J, Ploch M. Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S15-8.
6.Harrer G, Hubner WD, Podzuweit H. Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S24-8.
7.Holsboer-Trachsler E, Vanoni C. Clinical efficacy and tolerance of the hypericum special extract LI 160 in depressive disorders--a drug monitoring study. Schweiz Rundsch Med Prax. 1999 Sep 9;88(37):1475-80.
8.Hubner WD, Lande S, Podzuweit H. Hypericum treatment of mild depressions with somatic symptoms. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S12-4.
9.Jobst KA, McIntyre M, St George D, Whitelegg M. Safety of St John's wort. Lancet. 2000 Feb 12;355(9203):575
10.Johne A, Brockmoller J, Bauer S, Maurer A, Langheinrich M, Roots I. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther. 1999 Oct;66(4):338-45.
11.Kasper S. Treatment of seasonal affective disorder (SAD) with hypericum extract. Pharmacopsychiatry. 1997 Sep;30 Suppl 2:89-93.
12.Laakmann G, Schule C, Baghai T, Kieser M. St. John's wort in mild to moderate depression: the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry. 1998 Jun;31 Suppl 1:54-9.
13.Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D. St John's wort for depression--an overview and meta-analysis of randomised clinical trials. BMJ. 1996 Aug 3;313(7052):253-8.
14.Martinez B, Kasper S, Ruhrmann S, Moller HJ. Hypericum in the treatment of seasonal affective disorders. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S29-33.
15.Miller AL. St. John's Wort (Hypericum perforatum): clinical effects on depression and other conditions. Altern Med Rev. 1998 Feb;3(1):18-26.
16.Philipp M, Kohnen R, Hiller KO. Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks. BMJ. 1999 Dec 11;319(7224):1534-8.
17.Sommer H, Harrer G. Placebo-controlled double-blind study examining the effectiveness of an hypericum preparation in 105 mildly depressed patients. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S9-11.
18.Stevinson C, Ernst E. Hypericum for depression. An update of the clinical evidence. Eur Neuropsychopharmacol. 1999 Dec;9(6):501-5.
19.Volz HP, Laux P. Potential treatment for subthreshold and mild depression: a comparison of St. John's wort extracts and fluoxetine. Compr Psychiatry. 2000 Mar-Apr;41(2 Suppl 1):133-7.
20.Vorbach EU, Arnoldt KH, Hubner WD. Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Pharmacopsychiatry. 1997 Sep;30 Suppl 2:81-5.
21.Vorbach EU, Hubner WD, Arnoldt KH. Effectiveness and tolerance of the hypericum extract LI 160 in comparison with imipramine: randomized double-blind study with 135 outpatients. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S19-23.
22.Wheatley D. LI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients--a controlled 6-week clinical trial. Pharmacopsychiatry. 1997 Sep;30 Suppl 2:77-80.
23.Williams JW Jr, Mulrow CD, Chiquette E, Noel PH, Aguilar C, Cornell J. A systematic review of newer pharmacotherapies for depression in adults: evidence report summary. Ann Intern Med. 2000 May 2;132(9):743-56.
24.Woelk H, Burkard G, Grunwald J. Benefits and risks of the hypericum extract LI 160: drug monitoring study with 3250 patients. J Geriatr Psychiatry Neurol. 1994 Oct;7 Suppl 1:S34-8.
EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.