St. John’s Wort (Hypericum perforatum)



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6.0 /10

Mental Health

6.0 /10

St. John’s Wort (Hypericum perforatum)

Anxiety Support
Depression Support
Mental Health
Mood Support



What is St. John’s Wort?

St. John’s wort, or Hypericum perforatum, is a perennial, herbaceous shrub identifiable by its bright yellow flowers and clusters of protruding stamens. The plant has exhibited anti-inflammatory, antiviral, and possibly antidepressant properties in clinical research [1]. St. John’s wort is available in tablet and liquid form, and is also frequently used as a topical treatment for wounds and dermatological disorders such as eczema [2]. In recent years, significant clinical attention has been dedicated to St. Johns wort’s capabilities as a mood stabilizer [3].

Benefits and Effects

Adjuvant Treatment for Mild to Moderate Depression

The therapeutic association between St. John’s wort and depression has been well-documented, and the substance is commonly prescribed as an adjuvant treatment for depression in Europe [4]. The majority of clinical research recommends the herb as an additional treatment for mild to moderate symptoms over the short term [3].

In a placebo-controlled, randomized trial published by the Journal of Clinical Psychopharmacology in 2005, researchers evaluated the antidepressant efficacy of a St. John’s wort extract against placebo and the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Results yielded that, within the sample group of one hundred thirty-five patients, the St. John’s wort group alleviated depressive symptoms more effectively than both placebo and fluoxetine. Patients were evaluated based on the 17-item Hamilton Rating Scale for Depression [5].

A 2002 study published by the Journal of the American Medical Association produced similar results. This trial was conducted over a period of twenty-six weeks and revealed that, among one hundred twenty-four participants, St. John’s wort extract was effective in treating moderate depression. Parameters were established based on the Hamilton Rating Scale for Depression [3][6].

However, a 2011 clinical trial conducted over a period of twelve weeks found that St. John’s wort did not ameliorate depressive symptoms in seventy-three patients in comparison to placebo [3][7]. This trial was published by the Journal of Psychiatric Research [7].

Overall, clinical research examining St. John’s wort’s efficacy as an antidepressant has produced slightly mixed results. More long-term research is warranted [3].

Alleviation of Menopausal Symptoms

Some clinical research indicates that St. John’s wort may relieve menopausal symptoms in women. A 1999 study published by Advances in Therapy evaluated the therapeutic efficacy of St. John’s wort in one hundred eleven menopausal women over a period of twelve weeks. Researchers observed substantial improvements in psychological health, climacteric resilience, and sexual well-being among patients [8].

A more recent 2010 study published by The Journal of the North American Menopause Society produced similar results. Researchers evaluated the therapeutic efficacy of St. John’s wort in alleviating menopause-associated hot flashes among one hundred participants. Results indicated that, though the duration of hot flashes was not significantly changed at the fourth week of administration, St. John’s wort reduced both the severity and duration of hot flashes by the eighth week of treatment [9].

Topical Treatment for Eczema

A 2003 study published by Phytomedicine investigated the anti-inflammatory properties of topical St. John’s wort in patients with subacute atopic eczema. Researchers observed that, over a period of four weeks, the St. John’s wort cream significantly alleviated the severity of eczematous lesions in comparison to placebo [10].

Current research regarding St. John’s wort and its efficacy in treating various types of dermatitis is limited, but existing results warrant further investigation.

Wound Healing

In a 2017 study published by Comparative Clinical Pathology, researchers explored the topical wound healing activity of St. John’s wort in horses suffering from atopic skin lesions. Six horses of different breeds were treated with topical oil prepared from St. John’s wort, and researchers observed a complete resolution of wounds in all animals between weeks one and five. Hair re-growth was observed between twenty-five days and two months [11].

A 2015 study with diabetic laboratory rats suffering from excisional wounds produced similar results. Forty-eight female diabetic rats were randomly divided into control and placebo groups, the former of which was treated with a gel produced from St. John’s wort extract and examined every three days. Researchers found that St. John’s wort had the capacity to enhance fibroblast proliferation and collagen synthesis, thus escalating wound closure rate [12].

How Does St. John’s Wort Work?

St. John’s wort’s bioactive compounds include the following: napthodianthrones (hypericin, pseudohypericin, protohypericin, and cyclopseudohypericin), flavonoids (quercetin, luteolin, and rutin), and hyperforin, as well as a variety of pharmacologically potent amino acids [13]. It was previously believed that hyperforin was primarily responsible for the plant’s antidepressant potential, but recent research has indicated that its mood-regulating mechanism is likely multifactorial [13][14].

In vitro studies have revealed that St. John’s wort inhibits the synaptosomal uptake of serotonin, dopamine, and noradrenaline/norepinephrine, three neurotransmitters that are heavily implicated in clinical depression. St. John’s wort has also demonstrated affinity for adenosine, GABA, and glutamate receptors, all of which regulate the release of stress hormones as well as neuronal excitability [15].

In terms of wound and dermatological healing, it is believed that St. John’s wort’s mechanism of action is similar to that of Centella asiatica, a medicinal herbaceous plant indigenous to the wetlands of Asia [16][17]. Like Centella asiatica, St. John’s wort stimulates fibroblast collagen production, which aids cells in closing damaged wound areas and lesions [16].


The standard St. John’s wort dosage for depression in adults is 300 mg thrice daily [18]. However, patients should consult thoroughly with a trusted physician regarding what St. John’s wort dosage is likely to be safest and most effective for them.

Side Effects

Is St. John’s wort safe?

Overall St. John’s wort has a positive tolerability profile in healthy individuals. A safety assessment published by the European Journal of Clinical Pharmacology reviewed an international body of case reports and clinical trials and found that St. John’s wort did not have a significant adverse effects profile in comparison to placebo [19].

Though St. John’s wort is generally well-tolerated, some side effects alongside supplementation have been observed and include increased urinary frequency, gastrointestinal symptoms, lightheadedness, drowsiness, or confusion, and photosensitivity in rare cases [19][20].


St. John’s wort and birth control are contraindicated, as the plant has been demonstrated to reduce the efficacy of oral contraception. Other prescription medications that may be weakened by St. John’s wort include oxycodone, cancer medications such as Irinotecan, some anti-HIV treatments such as Indinavir, anticoagulants, and antidepressants (SSRIs, SNRIs, MAOIs, etc.). In turn, these medications may inhibit St. John’s wort effects as well [3].

While St. John’s wort and alcohol are not contraindicated specifically, the supplement may enhance the soporific effects of ethanol [21]. The relationship between the herb and alcohol are still being elucidated. A study published by Alcohol and Alcoholism observed that oral administration of St. John’s wort significantly attenuated alcohol intake and preference in high-alcohol drinking laboratory rats. This suggests that St. John’s wort may actually be a natural deterrent from alcohol [22].

Pregnant or breastfeeding individuals should avoid taking St. John’s wort. A study published by the Brazilian Journal of Pharmacognosy found that rats administered oral St. John’s wort during pregnancy produced offspring exhibiting behavioural abnormalities in adulthood. It is unknown if supplementation would produce the same effects in humans [23]. It has also been revealed in clinical research that St. John’s wort can be excreted into breast milk at low levels [24].


How do I take St. John’s wort?

St. John’s wort can be consumed orally in tablet or liquid extract form. Some individuals apply St. John’s wort oil to the skin in order to alleviate dermatological lesions or heal wounds. However, there is some risk involved in this as topical St. John’s wort can cause excessive photosensitivity [25].

How long does St. John’s wort take to work?

In cases of mild to moderate depression, St. John’s wort will typically take effect towards the end of the first week of supplementation [26]. It is said to reach maximum effect after approximately 6-8 weeks [27].

What is the best brand of St. John’s wort?

Individuals interested in taking St. John’s wort should be cognizant of product quality concerns. The most ineffective products will not contain adequate fractions of hyperforin and hypericin, which are among the herb’s most pharmacologically active compounds. Further, illegitimate supplements may be contaminated with heavy metals [28]. Regardless of brand reputation, a legitimate St. John’s wort supplement should contain .3% hypericin or 1-3% hyperforin [29].

What are the similarities between 5-HTP and St. John’s wort?

5-HTP, or 5-Hydroxytryptophan, refers to an essential amino acid and a chemical precursor to the neurotransmitter serotonin. It has been demonstrated in clinical research to have therapeutic benefits in instances of cerebellar ataxia, alcoholism, depression, anxiety, fibromyalgia, and sleep disorders [30]. Like St. John’s wort, 5-HTP is sometimes used as an adjuvant treatment for mild to moderate depression. Some patients advocate for combining St. John’s wort and 5-HTP supplements for an elevated antidepressant effect. However, to date no clinical studies have been conducted that verify the safety of this stack and all purported benefits are anecdotal [31].

Sam E vs. St. John’s wort: which is more effective for depression?

Sam E is the shorthand name for S-Adenosyl methionine, a naturally occurring cosubstrate that is heavily involved in the transfer of methyl groups in the brain and liver. Clinical research indicates that Sam E has therapeutic benefits for patients suffering from osteoarthritis, liver disease, and possibly psychiatric abnormalities [32].

The idea that Sam E may have therapeutic potential in clinical depression stems from research that has indicated abnormal levels of the cosubstrate in patients with depression and liver diseases [32]. However, research verifying its efficacy as an antidepressant is both limited and inconclusive [33]. A greater body of knowledge pointing to St. John’s wort as a mild antidepressant exists. Given limited data, it is not possible to make an accurate comparative assessment of St. John’s wort vs Sam E in treating depression.

Additional information

Weight0.125 kg


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Also known as:Hypericum Perforatum, Hypericum, Klamathweed Saint John’s Wort
Good for: , , , , , , ,
Stacks well with: 5-HTP,GABA
Typical dose:300 mg thrice daily
Half Life :Coming soon...