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PART V

Plant Profiles

ST. JOHNS WORT

Botanical name: Hypercium perforatum
Family name: Clusiacaea
Synonyms: St. Joans wort
Part used: Flowers, upper 6 to 8 inches of the aerial
portion of the herb, including leaf and flower

MAJOR CHEMICAL CONSTITUENTS

Hypericin, pseudohypericin, isohypericin, hyperforin;
flavonols including kaempferol and quercetin; flavones,
glycosides, bioflavonoids, catechins; phenols including
caffeic acid, p-coumaric acid, ferulic acid, and vanillic
avid; volatile oils, carotenoids, nicotinic avid, isovalerinic
acid, palmitic acid, and a number of volatile oils.

PRINCIPAL USES
 Mild to moderate depression
 Mild sedative and nerve tonic for excitability, anxiety,

and nervous irritability

 Mild sedative/analgesic for neuralgia and sciatica
 Antiviral for both internal and topical prevention and

treatment of Herpes simplex virus (HSV)

 Neurovegetative menopausal complaints
 Topical wound healing, for example, postpartum peri-

neal healing, hemorrhoids, sore. cracked nipples during

lactation, and vaginal abrasions in vaginitis and perimenopausal vaginal atrophy and associate vaginal
dryness
 Cystitis, urinary frequency and urgency, interstitial
cystitis

TRADITIONAL AND HISTORICAL USES

St. Johns wort (SJW) has been a famed vulnerary and
antidepressant herb since the Greco-Roman times. In
ancient medical history, however, depression was not
the likely diagnosisa patient was said to have been
afflicted by evil spirits or other psychic malady.
In our modern era, mounting evidence from clinical
trials, especially those conducted in the 1980s and 1990s,
established the efficacy and safety of standardized SJW
extracts for treating mild to moderate depression, and
practically overnight, SJW became a household alternative for the treatment of depression as well as a multimillion dollar boon for the natural products industry.
Although SJW remains a top-selling herb, reports of
potentially serious herbdrug interactions, as well as
widely publicized but poorly conducted studies questioning its efficacy have led to some decline in its popularity
as a treatment for depression.

CLINICAL INDICATIONS
SJW is indicated for mild to moderate depression.
Herbalists also prescribe SJW as a mild sedative and
nerve tonic for excitability, anxiety, and nervous irritability, for pain relief for neuralgia and sciatica, as an antiviral for both internal and topical prevention and
treatment of Herpes simplex virus (HSV), and for neurovegetative menopausal complaints, particularly anxiety
and sleep difficulties, typically in combination with
other herbs. It is commonly included as a vulneraryor

St. Johns wort (Hypericum perforatum). (Photo by Martin

Wall.)

wound healing herbin formulae for the treatment of

cuts, scrapes, and puncture wounds, as well as to soothe
and heal the perineum with or without perineal lacerations after childbirth, to soothe and reduce hemorrhoids,
and for the treatment of vaginal abrasions in vaginitis
and those that can occur with perimenopausal vaginal
atrophy and vaginal dryness. Herbal practitioners
may also include SJW in formulae for the treatment of
cystitis, urinary frequency and urgency, and interstitial
cystitis.

MECHANISMS OF ACTION
The precise mechanisms of action for the antidepressant
effects of SJW are not understood. In vitro studies using
hyperforin have demonstrated significant binding of
GABA A and GABA B, adenosine, MAO, and benzodiazepine receptors. Only GABA A and GABA B receptor activity is likely to be achieved in concentrations to elicit a
biological effect after oral administration in humans.
Early studies focused on the inhibitory activity of hypericin on MAO receptors; however, most studies have
demonstrated only weak binding if at all. It appears
that there might be some effects in inhibition of synaptosomal uptake of serotonin (5-HT), dopamine, and noradrenaline, with an upregulation of 5-HT in rat cortex,
with some increase in dopamine and noradrenaline.
Studies have shown possible decrease in tryptophan
degradation; tryptophan is a 5-HT precursor. Another
possible explanation for the antidepressant effect of

ST. JOHNS WORT

SJW is via inhibition of interleukin-6 (IL-6) by hyperforin

and via inhibition of substance P mediated effects on
depression.
Antiviral effects of SJW are attributed in part to the
flavonoid and catechin fractions of the herb. Both hypericin and psuedohypericin have demonstrated in vitro
inhibition of HSV Types 1 and 2, Varicella zoster virus,
and HIV type 1 via a photoactivation process that is not
yet elucidated.
Tannins in SJW have a mild astringent effect and may
help to explain some of the vulnerary effects, as well as
use in the treatment of hemorrhoids. A quercetin-like
compound in SJW has been attributed with possible analgesic effects of the herb. SJW extract has also been
observed to suppress inflammation and leukocyte infiltration in murine models. Hypericin has demonstrated
in vitro ability to inhibit tumor necrosis factor induced
activation of NF-kappa B and the release of arachadonic
acid, as well as inhibition of 5-lipoxygenase and COX-1.
SJW may have free-radical scavenging activity; however,
this has not been a consistent finding in studies.

RATINGS
 Botanical Safety Handbook rating 2d: Not for use

during phototherapy; interaction Class C. Herbs for

which clinically significant interactions are known to
occur
 German Commission E: Internal uses include the treatment of psychovegetative disturbances, depressive
moods, anxiety and/or nervous unrest. External: Oilbased preparations for the treatment of acute and contused injuries, myalgia, and first-degree burns.

PREPARATIONS USED CLINICALLY






Dried herb in tea and capsules

Tincture
Standardized extract
Oil extract for topical use

DOSAGE
 Dried herb: 2 to 4 g as an infusion three times daily
 Tincture: 2 to 4 mL 3x daily
 Clinical trial doses: 240 to 1800 mg daily standardized

to varying concentrations of hypericin and hyperforin

for a minimum of 4 to 6 weeks. Dosing in depression
clinical trials suggests a starting dose of 300 mg of SJW
standardized to 0.3% hypericin (and possibly also to
25% hypericin) 3x daily with a maintenance dose of
300 to 600 mg per day.
 Topical use as needed

SAFETY INFORMATION: HERB DRUG

INTERACTIONS, TOXICITY, AND
CONTRAINDICATIONS
St. Johns wort is considered a generally well-tolerated
herb, even when taken continuously for up to 8 weeks.
Adverse reactions are usually mild and included skin reactions, GI symptoms, fatigue, sedation, restlessness, dizziness, dry mouth, and headache with few side effects,
most notably photosensitivity and mania, reported in
clinical trials. Studies of chronic toxicity in animals

545

have shown only nonspecific symptoms such as weight

loss. Rarely, skin reactions such as pruritus and rash have
been reported, with a drug monitoring study of 3250
patients showing 17 allergic reactions.
A European review of adverse reactions from 1991 to
1999 involving nearly 8 million people documented only
95 adverse reactions. Three case reports in the literature
suggest the possibility of phototoxicity; in patients taking
SJW. Two of the cases involved patients receiving laser or
UVB treatments. Phase 1 trials of IV and oral hypericin in
adult patients with HIV demonstrated severe cutaneous
phototoxic reactions in 11 of 23 subjects, and a variety
photosensitivity reactions in 14 of 19 hepatitis C
patients. Several additional studies have confirmed similar findings particularly at high doses of hypericin or high
UVA light. One study did not find phototoxic effects.
Patients receiving UV treatment are advised to avoid
SJW use during treatment and those with fair skin are
advised to avoid sun exposure of skin while taking SJW
internally or topically.
Anorgasmia has been reported in 25% of patients
taking 900 to 1500 mg SJW daily for 8 weeks versus
32% taking sertraline and 16% taking placebo, in additional to 2 published case reports of sexual dysfunction in
patients taking the herb for mood disorders. Frequent
urination was also seen in 27% of patients taking 900
to 1500 mg SJW daily for 8 weeks vs. 21% taking sertraline and 11% taking placebo.
SJW, through its actions on the hepatic metabolism of
drugs, specifically via induction of the cytochrome
system, may lead to changes in the plasma level of a
number of drugs, preventing a patient from achieving
appropriate therapeutic levels. There is evidence from
clinical trials and case reports that SJW may interact
with the following medications:
 Antiarrhythmics/calcium channel blockers: May lead to
decreased plasma levels of digoxin, verapamil, and
nifedipine
 Anticonvulsants: May lead to decreased plasma levels
phenytoin
 Anticoagulants: May lead to decreased plasma levels
warfarin
 Antidepressants: May lead to decreased plasma levels
amitriptyline (a tricyclic antidepressant) and the SSRIs
paroxetine, fluoxetine, and trazadone. Serotonin syndrome can result from reduced serum levels of SSRIs.
 Antihistamines: Fexofenadine (single dose may
increase while continued use may decrease plasma
level of drug)
 Antipsychotics and anxiolytics: May lead to decreased
plasma levels of buspirone, quitazepam, midazolam,
and alprazolam
 Antiulcer agents: May lead to decreased plasma levels of
omeprazole
 Antivirals: May lead to decreased plasma levels of
indinavir
 Chemotherapeutic agents: May lead to decreased
plasma levels of irinotecan and imatinib
 Hormonal contraceptives: May lead to decreased
plasma levels of hormonal birth control/oral
contraceptives

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PART V

Plant Profiles

 Immunosuppressants: May lead to decreased plasma

levels of cyclosporine and tacrolimus

 Reverse transcriptase inhibitors: May lead to decreased
plasma levels of nevirapine
 Skeletal muscle relaxants: May lead to decreased plasma
levels of chlorzoxazone
 Statins: May lead to decreased plasma levels of
simvastatin

WARNING
Patients taking cyclosporine for the prevention of transplant rejection or other medical reasons should avoid the
concurrent use of SJW as it has been shown to interfere
with immunosuppressant medications.
Patients taking medications metabolized by CYP450
should avoid SJW or consult with the physician prior
to use.
Caution is advised with SJW use for patients with fair
skin, receiving photosensitizing drugs, or receiving UV
treatments. At recommended doses of whole plant
extracts, the risk of photosensitization appears to be
quite low.
Activation may occur in patients with a history of
mania, bipolar disorder, and other mood disorders.
SJW is suggested for the treatment of patients with
mild to moderate depression, not severe depression or
suicidality.
Cases of possible serotonin syndrome has been
reported in patients taking SJW.

USE IN PREGNANCY AND LACTATION

Because of lack of clinical trials and safety data, SJW is not
commonly recommended for the treatment of mood disorders during pregnancy. Its use is more often reserved
for topical treatment of vaginitis, in the treatment of perineal tears, and for the treatment of sore, cracked nipples
during lactation.
It is becoming increasingly well established that
untreated depression in pregnant women and new
mothers can have significant health and social consequences for their offspring. Comparative studies on the
efficacy and safety of SJW compared to pharmaceutical
antidepressants for the treatment of prenatal and postpartum depression are needed.
Murine and rat studies on the prenatal consumption
of SJW have been generally associated with normal gestation and fetal development. In one study, male offspring in a SJW exposed group had a statistically
significant lower birth weight than the placebo group,
however, by three days after birth the difference was
not statistically significant. The males in the SJW group
also demonstrated a statistically significant temporary
delay in the appearance of upper incisors. In another
rat study females were given a methanol extract of SJW
standardized to 0.3% hypericin at 100 or 1000 mg/kg

or placebo by gavage for 2 weeks prior to conception,

throughout gestation, and/or for 3 weeks during lactation. Histological evidence of hepatic and renal changes
was seen in the SJW exposed group, with more severe
lesions in the rat pups whose dams received higher
doses and the offspring of those receiving both SJW
in both pregnancy and lactation. No significant impact
on cognitive behaviors have been seen in the offspring of
mice given SJW throughout gestation. A slight increase
in in vitro uterotonic activity has been reported with
SJW use.
Overall there is a lack of toxicity studies conducted on
SJW use during pregnancy. A limited number of human
case reports indicated healthy pregnancies and infants
when SJW was used prenatally. In a small prospective
cohort safety study of breastfeeding women (n = 33)
who took SJW products during pregnancy and who contacted a toxicology advise service, compared to 101
matched controls who had also contacted the service
but had not taken SJW, there were no maternal adverse
effects, no statistically significant differences in women
reporting decreased breast milk volume, and no medical
problems in the offspring. Two of the infants born to
mothers taking SJW experience colic, drowsiness, or lethargy compared with the other group; a number of these
infants were also reported to have been exposed to conventional antidepressant medications while breastfeeding. Limitations to this report include lack of product
identification or quantification in this report, and
the number of women taking SJW while pregnant was
small.
Hyperforin was detected in low concentrations in the
breast milk who took 300 mg of SJW three times daily
starting at 5 months postpartum for the treatment of
postpartum depression. No adverse effects were seen in
her baby. The clinical significance to the infant of SJW in
breast milk is unknown; no adverse effects have been
reported. Use of topical applications of SJW oil or salve
as treatment for sore, cracked nipples, particularly if wellabsorbed with any excess wiped off prior to nursing does
not appear harmful to the infant. See warnings in the
preceding regarding interactions with immunosuppressant and other medications.
The safety of SJW taken internally during pregnancy
and breastfeeding, both in terms of effects on the mother
and her child, are unknown at this time. Because of this,
the herb is generally not recommended for internal consumption during pregnancy and lactation. Given the
widespread incidence of depression in society, and the
relatively high incidence and serious consequences of
postpartum depression on the health of mother, baby,
and their relationship, as well as the family overall,
research in to SJW for prophylaxis and treatment
of depression during the childbearing years should be
explored in carefully controlled studies.