What is St. John's wort?
 
   

What is St. John's wort?

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:
   Frankp@chiro.org
 
   

Thanks to the University of North Carolina School of Pharmacy for the use of this article!

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.


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