Benefits (and Risks) of St. John’s Wort for Depression

St. John’s wort is a popular remedy for depression, however it has many side effects and interactions. Get the latest facts and learn about alternatives.

What Is St. John’s Wort?

St. John’s wort (Hypericum perforatum) is a low-growing ground cover plant that is blanketed with cheerful yellow flowers around the time of St. John the Baptist’s birthday late in June.

Hypericum literally means “about spirits” as this plant was believed to contain magical properties that could ward off evil spirits. (2)

It has a 2,000-year-old history as a natural remedy and was mentioned in the works of Hippocrates and Pliny.

Traditionally it was used both externally and internally to treat conditions as diverse as wounds, burns, snakebites, nervous disorders, ulcers, melancholy, tumors, and sciatica. (3, 4, 5)

Modern-day uses based on scientific theory and expert opinion include using St. John’s wort for alcoholism, athletic performance enhancement, benzodiazepine withdrawal, cancer, chronic ear infections, Epstein-Barr virus, substance abuse, and ulcers. (6)

By far the most common use today, however, is as an herbal remedy for depression.

In spite of its popularity though, there is currently no consensus that St. John’s wort is a safe or effective natural antidepressant.

In Germany, where St. John’s wort is available by prescription, doctors prescribe it 20 times more often than Prozac. (7)

Conversely, in some countries it’s been banned or restricted due to a plethora of unwanted side effects.

Their review of 29 international studies concluded that St. John’s wort may be as effective as standard prescription antidepressants for depression with fewer side effects than antidepressants.

Interestingly, studies conducted in German-speaking countries reported more positive results than those done elsewhere.

The reason for this is unclear.

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It may be that better forms of St. John’s wort are used in these countries.

Or it could, in part, be a placebo effect since study participants in those countries were predisposed to believing its effectiveness.

But more recent studies on St. John’s wort for depression have failed to produce the same results.

One study sponsored by the US National Institute of Mental Health found that St. John’s wort did not decrease symptoms of minor depression any better than a placebo. (9)

But surprisingly, the prescription antidepressant that was also tested did not work better than a placebo either!

A second NIMH study found similar results for treating major depression.

What About St. John’s Wort for Anxiety?

Anxiety is another common condition for which people take St. John’s wort, but there’s little evidence that it is helpful. (10)

In fact, one of the more common side effects of St. John’s wort is anxiety and even panic attacks! (11)

If anxiety is your main concern, it’s best to avoid St. John’s wort and try one of the many proven supplements for anxiety instead.

How St. John’s Wort Works to Alleviate Depression

St. John’s wort is the most widely studied herbal remedy for depression, yet it’s still not understood exactly how it works.

It contains dozens of bioactive compounds, but the two most important ones are hypericin and hyperforin. (12)

Hyperforin boosts numerous mood-related brain chemicals including serotonin, dopamine, noradrenaline, GABA, and glutamate.

It helps serotonin, the neurotransmitter most commonly associated with depression, bind to serotonin receptors.

It also increases the number of serotonin receptors in the brain.

Flavonoids are another group of beneficial plant compounds found in St. John’s wort.

They may help to ward off depression by protecting the brain with their potent antioxidant and anti-inflammatory properties.

St. John’s Wort Risks: Side Effects, Cautions, and Interactions

Compared to many natural remedies, St. John’s wort is rife with side effects, cautions, and especially drug interactions.

Here is what you need to know to determine if St. John’s wort is safe for you and whether the downside outweighs the potential benefits.

St. John’s Wort Side Effects

One of the main reasons people want to try St. John’s wort instead of a prescription antidepressant is to avoid side effects.

But ironically, the list of St. John’s wort side effects is very similar to those of antidepressant medications — anxiety, panic attacks, dizziness, nausea, and spikes in blood pressure. (13)

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Other reported side effects include allergic reactions, vomiting, dizziness, aggression, headache, fatigue, memory loss, mental confusion, dry mouth, and constipation. (14, 15)

A most concerning side effect is photosensitivity.

One of St. John’s wort main active ingredients, hypericin, is highly photoreactive.

Sometimes St. John’s wort taken with a medication can cause side effects, while at other times it can cause your drug to stop working.

You might be tempted to use St. John’s wort to taper off your antidepressant, but you should never mix the two.

Together they can cause a rare but serious condition called serotonin syndrome.

St. John’s wort can weaken the effects of many prescription medicines, including those that treat cancer, heart disease, and HIV. (19)

Ladies, be aware that St. John’s wort can cause your birth control pills to stop working!

It may seem odd that a natural substance can interact with so many medications but you’re probably familiar with a similar scenario.

It’s well-known that many medications should not be taken if you eat grapefruit or drink grapefruit juice. (20)

St. John’s wort, much like grapefruit, interferes with drugs by affecting the activity of certain enzymes.

St. John’s wort should also be avoided by women who are pregnant or breastfeeding.

Lastly, do not take it if you have schizophrenia or bipolar disorder as it can trigger episodes of mania. (21)

St. John’s Wort and Food Reactions

Some people experience reactions with St. John’s wort when eating foods high in the amino acid tyramine.

Foods that have been pickled, aged, smoked, or fermented are highest in tyramine.

This includes beer and wine, many kinds of cheese, aged or cured meat, sauerkraut, fermented soy products, and chocolate. (22)

The combination of tyramine-rich foods and St. John’s wort is especially dangerous for anyone with high blood pressure.

It’s also advised that you avoid alcohol and minimize caffeine intake when supplementing with St. John’s wort. (23)

St. John’s Wort Interactions with Supplements

St. John’s wort does not safely mix with all other natural supplements either.

St. John’s wort should not be taken with 5-HTP, another popular supplement for depression, anxiety, and insomnia.

When taken together, there’s a risk of serotonin syndrome.

Worryingly, many multi-ingredient mood-enhancing supplements contain both St. John’s wort and 5-HTP.

You should avoid these.

St. John’s wort works synergistically with many other herbs to enhance their beneficial actions.

But this property cuts both ways since it also increases the risk for and severity of side effects should they occur.

What to Look for in a St. John’s Wort Supplement

If you decide to give St. John’s wort a try, you’ll find a wide array of tablets, capsules, liquid extracts, dried herbs, oils, and teas available.Most will be standardized to contain 0.3% hypericin. (25)

The Best St. John’s Wort Supplement

Interestingly, the standardization of hypericin has lead to the erroneous belief that it is St. John’s wort’s main active ingredient.

But in fact there’s no strong evidence that hypericin is responsible for St. John’s wort antidepressant properties. (27)

It seems that most of St. John’s wort pharmacological properties come from hyperforin rather than hypericin.

Yet almost all supplements contain a standardized extract of hypericin, not hyperforin.

This is because hypericin was discovered first and has been studied longer and is a more stable compound than hyperforin.

However, there is one patented brand of hyperforin that uses a stabilizing technology — Perika (WS 5570).

This is the same form used in Germany where St. John’s wort is considered to have substantial medicinal value. (28)

The only readily available supplement I’ve found that contains this is Nature’s Way Perika St. John’s Wort.

Whatever form you decide to take, be sure to buy a reputable brand.

Sixty percent of the St. John’s wort supplements tested by the independent watchdog group ConsumerLab.com did not contain what was stated on the label. (29)

You can’t expect to reap any of St. John’s wort’s benefits with an inferior product.

St. John’s Wort Dosage

The accepted dose of St. John’s wort is 300 mg of standardized extract (0.3% of hypericin) taken 3 times per day. (30)

Doses up to 1,800 mg per day have been used for moderate to severe depression. (31)

If you are taking the whole dried herb, you can take 2 to 4 grams per day. (32)

Be patient when trying St. John’s wort.

It takes a while for its beneficial effects to kick in, often a few weeks or more.

But if you don’t experience a noticeable reduction in depression symptoms after 6 weeks, it’s advised that you stop taking it. (33)

Safer, More Effective Alternatives to St. John’s Wort 

You may now understandably be leery of taking a St. John’s wort supplement.

If you are currently taking it with success, then stick with it.

But if you are one of the millions of people for whom St. John’s wort is not a viable option, rest assured that there are many alternatives.