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

Edited and medically reviewed by Patrick Alban, DC | Written by Deane Alban

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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.

St. John’s wort is one of the most popular natural treatments for depression. 

Worldwide, billions of dollars of St. John’s wort supplements are sold every year, making it relatively mainstream for an alternative remedy. (1)

But this popular herb is not without controversy.

In some parts of the world, it’s thought to be so potent that it’s available only by prescription.

But in others, it’s banned or restricted due to the number of unwanted side effects and interactions.

Before you take St. John’s wort, you need to know two things: Is it safe? And is it effective?

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 in late 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)

Based on modern-day scientific theory and expert opinion, St. John’s wort is now used for alcoholism, athletic performance enhancement, benzodiazepine withdrawal, cancer, chronic ear infections, Epstein-Barr virus, substance abuse, and ulcers. (4)

But the most common use today, by far, is as an herbal remedy for depression.

In Germany, where St. John’s wort is available by prescription, doctors prescribe it 20 times more often than Prozac. (5)

In the United States, it’s readily available as an OTC supplement or an herbal tea.

An interesting aside is that in some western US states, St. John’s wort eradication programs are underway because it’s potentially deadly to livestock that graze on it. (6)

The Evidence for St. John’s Wort and Depression

There have been several reviews of St. John’s wort studies which together have covered nearly 100 human trials. (7, 8, 9)

These reviews of international studies have concluded that St. John’s wort seems to be similarly effective as typical prescription antidepressants, but with fewer side effects.

" Ironically, the list of St. John’s wort’s side effects is very similar to those of antidepressant medications.

A US National Institute of Mental Health review of studies found the results on St. John’s wort to be mixed.

One study that this organization sponsored found that neither St. John’s wort nor the prescription antidepressant it was being compared to worked better than a placebo. (10)

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

The reason for this is unclear.

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

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

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What About St. John’s Wort for Anxiety?

You may have heard that St. John’s wort can be taken for anxiety, but there’s little evidence that it is helpful.

In fact, one of the more common side effects of St. John’s wort is anxiety and even panic attacks. (11, 12)

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 fully understood how it works.

It contains dozens of bioactive compounds, but the two most important ones are hypericin and hyperforin. (13)

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 fend off depression by protecting the brain with their potent antioxidant and anti-inflammatory properties.

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

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

Here is what you need to know to determine if St. John’s wort is safe for you and whether its downside outweighs its 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’s side effects is very similar to those of antidepressant medications — anxiety, panic attacks, dizziness, nausea, and spikes in blood pressure. (14)

Other reported side effects include allergic reactions, vomiting, dizziness, aggression, headache, fatigue, memory loss, mental confusion, dry mouth, and constipation. (15, 16, 17)

A very concerning side effect is photosensitivity.

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

This can create a rash similar to sunburn with even minimal sun exposure.

This property of hypericin can also endanger your eyes by leading to damage of the lens or retina. (18)

Caution: If you take St. John’s wort, it’s critical that you protect your eyes from sunlight.

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St. John’s Wort and Drug Interactions

St. John’s wort is known to react badly with hundreds of medications. (19)

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

St. John’s wort can weaken the effects of many prescription drugs, including antidepressants, blood thinners, painkillers, and those that treat cancer, heart disease, and HIV. (20)

Women must be aware that St. John’s wort can cause their birth control pills 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.

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 along with grapefruit or grapefruit juice. (21)

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. (22)

Caution: If you take any medications, you should not take St. John’s wort until you’ve discussed it with your doctor or pharmacist.

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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. (23)

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. (24)

Unless you are willing to forgo tyramine-rich foods, caffeine, and alcohol, you should steer clear of St. John’s wort supplements.

St. John’s Wort’s Interactions With Supplements

St. John’s wort does not safely mix with many 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.

Here’s a list of some of the most popular herbs that can interact with St. John’s wort: (25)

  • ashwagandha
  • capsicum
  • German chamomile
  • goldenseal
  • gotu kola
  • hops
  • kava
  • lemon balm
  • sage
  • scullcap
  • Siberian ginseng
  • stinging nettle
  • valerian
  • yerba mansa

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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. (26)

Others will contain dried flowers and leaves of the St. John’s wort plant.

Here’s a typical St. John’s wort supplement label:

st john's wort supplement label
St. John’s wort supplement label.

The first ingredient is the standardized hypericin extract.

The second ingredient is the whole dried leaves and flowers.

The term aerials simply means the above-ground parts of the plant (not the roots).

The Best St. John’s Wort Supplement

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

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

It seems that most of St. John’s wort’s 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). (28)

This is the same form used in Germany where St. John’s wort is considered to have substantial medicinal value. (29)

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. (30)

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. 

Clinical studies have used doses of up to 1,800 mg per day for moderate to severe depression. (31)

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

Be patient when trying St. John’s wort.

It can take a few weeks to notice any improvement in depression symptoms.

However, if you don’t experience any positive effects in 4 to 6 weeks, it’s advised that you stop taking it. (33)

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

Understandably, you may now 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.

You can also use proven antidepressant activities such as yoga, breathing exercises, neurofeedback, or mindfulness meditation.

Benefits of St. John’s Wort: Take the Next Step

St. John’s wort is a very popular herbal remedy for depression, but there are better alternatives.

It may be effective, but it has many side effects and negative interactions.

St. John’s wort’s side effects can be similar to those of antidepressant medications.

It should also not be mixed with hundreds of medications, certain herbal remedies, and even some foods.

There are many other natural remedies for depression with better records of effectiveness and safety.

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