St. John's Wort

(hypericum perforatum)

Chad Bradshaw, Anh Nguyen, and Jeff Surles

Description

• Shrubby, perennial plant
• Bright yellow flowers
• 1-3 feet tall erect plant
• Leaves and flowers contain medicinal effects

Other Common Names

• Goat Weed
• Klamath Weed
• Rosin Rose
• Amber touch and heal
• Tipton Weed
• From botanic family: hypericaceae

Regions of Growth

• Europe
• Britain
• North Africa
• Australia
• New Zealand
• Canada

History of St. John's Wort

• Hypericum perforatum: Greek for "over an apparition"
• Belief that the herb is "magical" because of its noxious odor
• Supposedly, evil spirits disliked the plant's odor, and thus could be warded away

Religious History

• Named after Saint John the Baptist
• The red spots on the leaves are symbolic of the blood of St. John
• Appeared on leaves on the anniversary of the Saint's beheading
• Therefore, best day to harvest plant: June 25

Other Interesting Historical Pieces...

• Sleep with the plant under your pillow on St. John's Eve: ensures vision of Saint John and obtains his blessing to prevent one's dying during the following year
• Soak plant in olive oil: symbolic of the blood of Christ
• Herbal remedy since the Middle Ages

Folk Uses

Early Applications

• nerve tonic: oldest indication
• neuralgia, mild to moderate depression, anxiety
• neuroses and insomnia

Recent Applications

• cancer treatment, AIDS
• diarrhea, nausea, sciatica, wound treatment, gastritis

Active Components

Hypericin:

• Treatment of depression
• Increases capillary flow

Other active compounds:

• Pseudohypericin: antiretroviral activity
• Tannins: for astringent effect
• Flavonoids, xanthones, phenolic carboxylic acids, essential oils, carotenoids, medium chain fatty acids

Pharmacology

• Antidepressant Activity

• Mechanism of Action?

• Antiviral Activity (in vitro)

• Herpes simplex virus types 1 and 2
• Influenza types A and B
• Vesicular stomatitis virus
• Epstein-Barr virus
• HIV?

• Antibacterial Activity - broad spectrum against both gram + and gram -

• Staphylococcus aureus
• Streptococcus mutans
• Proteus vulgaris
• Escherichia coli
• Pseudomonas aeruginosa

Clinical Applications

Depression

• Standardized extract containing 0.14% hypericin
• Has been used pharmacologically in Germany for years
• Doses of 300 mg TID are as effective in relieving symptoms of depression as standard antidepressants, but is much better tolerated with fewer side effects

AIDS & Other Viral Infections

• SJW may be a useful adjunctive treatment for herpes simplex, mononucleosis, and influenza
• Further human studies are needed to determine the optimal dosage
• May be a promising treatment for chronic fatigue syndrome

Numerous studies:

• 18 HIV patients received 2 mg hypericin/day
• Showed stable and increasing T-cell counts over the 40 months follow-up
• Most noteworthy: only 2 of the 16 encountered an opportunistic infection during the 40 month follow-up

• Trials so far have been disappointing
• Significant blood levels of hypericin could not be achieved using either oral or IV extracts
• Studies are now using a synthetic hypericin which is showing encouraging results in preliminary studies

Topical Applications

• Long been used as a wound-healing substance
• Antibacterial activity
• Have been used to treat burns and muscular pain
• Oily preparations preferred

Dosage

• Standardized fluid extract

• 300 mg TID

• Standardized solid (powdered dry) extract

• 0.3% hypericin: use 300 mg TID with meals

• Dried flowers

• 500-1000 mg

• Tincture

• 1-4 mL TID

• Dried herb infusion (tea): 1-2 grams

• Infusion Recipe

1-2 teaspoonfuls of dried herb to a cup of boiling water; Infuse for 10-15 minutes;

Use TID

Toxicity

• Has caused severe photosensitivity in animals that graze extensively on the plant
• Reports in humans rare; limited to those taking excessive quantities for HIV
• Tyramine-containing foods?
• Drugs such as L-dopa and 5-HT
• Take with food to avoid mild gastric upset

Mechanism of Action

Antiviral:

• Inhibition of assembly or processing of intact virions from infected cells; released with no reverse transcriptase
• Directly inactivates mature and properly assembled retroviruses

Depression

• MAO Inhibitor?
• SSRI?

In Vitro Study

Thiede HM and A. Walper. Inhibition of MAO and COMT by Hypericum Extracts and Hypericin. J Geriatr Psychiatry Neurol 1994; 7(suppl 1): S54-S56.

Aim: to investigate the effects of hypericum and its fractions on in vitro activity of MAO and COMT

Fractions:

• Petroleum ether:ether (1:1)
• Ether
• Ether:acetone (8:2)
• Acetone
• Methanol:acetone (1:1)
• Methanol
• Fractions contained different constituents

Conclusions from Study

• To attribute inhibitory effect of MAO to hypericin, the inhibitory effect of the whole extract would need to have been 100 to 1000 times weaker
• However, concentrations of the whole extract required to inhibit MAO were actually 100 times lower (Lower concns of whole extract provided MORE enzyme inhibition that fractions of hypericin alone)
• Thus, other constituents must have contributed to the inhibition
• In vitro concentrations of hypericin that inhibit MAO are in no way adequate to explain the antidepressant effect of the hypericum
• Implies that other constituents as well as other mechanisms of action must be responsible for the antidepressant effect of hypericum.

Mechanism of Action

• MAO may be inhibited to a small extent.
• Unlikely that this is the mechanism of antidepressant effect

Clinical Trial 1

Vorbach e., Hubner, W, and K.H. Arnoldt. Effectiveness and Tolerance of the Hypericum Extract LI 160 in Comparison with Imipramine: Randomized Double-Blind Study with 135 Outpatients. J Geriatr Psychiatry Neurol 1997; 7(suppl 1): S19-S23.

• Study conducted from October 1992 to May 1993
• Multi-Centered (20), randomized, double-blinded
• Sample size = 135; 130 completed study
• Groups were not significantly different

Dosage:

• St. John's Wort: 3 x 300 mg
• Imipramine: 3 x 25 mg (usual dose of imipramine is 50-150 mg)
• Capsules were indistinguishable in form, color, taste, and consistency

Study duration: 6 weeks

Inclusion Criteria:

• Typical depression according to DSM-III-R with a single or recurrent episode(s)
• Neurotic depression
• Adjustment disorder with depressed mood

Exclusion Criteria:

• Severe depression requiring inpatient treatment
• Schizophrenia or marked agitation requiring additional drug therapy
• Known history of attempted suicide or acute suicidal state

Target Variables:

• Hamilton Depression Scale (HAMD)
• Von Zerssen Depression Scale (D-S)
• Clinical Global Impressions (CGI)
• Compliance monitored by counting number of returned capsules

Results

Hamilton Depression Scale

• SJW: 56% improvement (20.2 to 8.8)
• Imipramine: 45% improvement (19.4 to 10.7)

Von Zerssen Depression Scale

• SJW: 39.6 to 27.2
• Imipramine: 39.0 to 29.2

Clinical Global Impressions (CGI)

Therapeutic Effect

• SJW: 1.3 to 3.1
• Imipramine: 1.2 to 2.7

Change in severity of illness

• SJW: 81.8% improved, 18.2% unchanged
• Imipramine: 62.5% improved, 34.4% unchanged

Change in Status Following Treatment

• SJW showed a slightly larger magnitude of positive change

Undesired Effects

Experienced by 8 patients on SJW (11.9%)

• 11 symptoms, most frequently being dry mouth and dizziness

Experienced by 11 patients on Imipramine (16.2%)

• 22 symptoms, most frequently being dry mouth, dizziness, anxiety, and constipation)

Other Effects

• No clinically relevant changes in either group with respect to BP, HR, HGB, RBC, Leukocytes, platelets, WBC (including differential), AST, ALT, Alkaline phosphatase, or creatinine)

Conclusion

• Hypericum (St. John's Wort) extract proved to be as efficacious as Imipramine with fewer adverse effects

Clinical Trial 2

Sommer H and G Harver. Placebo-Controlled Double-Blind Study Examining the Effectiveness of an Hypericum Preparation in 105 Mildly Depressed Patients. J Geriatr Psychiatry Neurol 1994; 7(suppl 1): S9-S11.

• Multicenter (3), Randomized, Double-Blind study

Admission criteria:

• 25-65 years old
• with depressive symptoms according to ICD-09 300.4 (neurotic depression) and 309.0 (brief depressive reaction)

Exclusion Criteria:

• Severe renal or hepatic dysfunction
• Heart failure
• Parkinson's Disease
• Endocrine or CNS tumors
• Alcohol/Drug/Medication dependency
• Pregnancy or lactation
• Prior psychoactive drug use within 4 weeks

Dose:

• 3 x 300 mg SJW
• Placebo

Results:

• Responder classified as one whose total HAMD score fell to less than 10 or by 50% of baseline value
• 96 patients completed the trial
• Both groups displayed similar HAMD scores
• By week 2, significant improvement in both groups
• By week 3, placebo group only slightly improved, whereas SJW group continued to improve steadily
• SJW particularly helped with these symptoms:

• Feelings of sadness, hopelessness, helplessness, worthlessness
• Difficulty initiating sleep/Disordered sleep
• Psychological anxiety
• Feelings of guilt

• Responders:

• 67% of patients in SJW group
• 28% of patients in placebo group

• Undesired Effects: Occurred in two patients on SJW

• Skin Reddening
• Itching
• Fatigue

Conclusion:

• Hypericum extract is a low risk antidepressant for treatment of mild and moderate depression, with the advantage of reliable antidepressant efficacy and a minimum of side effects.

In conclusion...

• St. John's Wort has shown antidepressant effects equal to conventional pharmaceutical agents, with fewer side effects.
• The mechanism of action of St. John's Wort is not fully understood.