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.
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.
But this popular herb is not without controversy.
In some countries, 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.
In Greek, Hypericum means “over an apparition” as this plant was believed to contain magical properties that could ward off evil spirits.
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 insomnia, wounds, burns, snakebites, nervous disorders, melancholy, tumors, and intestinal parasites.
Recent research suggests that Hypericum perforatum may be useful in treating numerous ailments, including ulcers, cancer, Alzheimer’s, Parkinson’s, opiate withdrawal, eczema, and menopause.
But the most common use today, by far, is as an herbal remedy for depression.
In Germany, where Hypericum perforatum is available by prescription, doctors prescribe it 20 times more often than Prozac.
In the United States, it’s readily available as an herbal tea or over-the-counter supplement.
An interesting aside is that in some western US states, Hypericum perforatum eradication programs are underway because it’s potentially deadly to livestock that graze on it.
The Evidence for Depression
There have been several reviews of Hypericum perforatum studies which together have covered nearly 100 human trials.
These reviews of international studies have concluded that Hypericum perforatum 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 review of studies by the US National Institute of Mental Health found mixed results regarding Hypericum perforatum.
One study sponsored by this organization found that neither St. John’s wort nor the prescription antidepressant it was compared to showed better effectiveness than a placebo.
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 Hypericum perforatum are used in those countries.
Speculation suggests this might be due to the placebo effect, given that study participants in those countries were predisposed to believing in its effectiveness.
What About for Anxiety?
While Hypericum perforatum may be recommended for anxiety, there’s limited evidence supporting its effectiveness.
In fact, one of the more common side effects of Hypericum perforatum is anxiety and, in rare cases, can even bring on panic attacks.
If anxiety is your main concern, it’s best to avoid Hypericum perforatum and try one of the many proven supplements for anxiety instead.
How Does it Work to Alleviate Depression
Hypericum perforatum, the most widely studied herbal remedy for depression, still lacks a complete understanding of its mechanism of action.
It contains dozens of bioactive compounds, with the two most important ones being hypericin and hyperforin.
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 present in Hypericum perforatum.
They may help to fend off depression by protecting the brain with their potent antioxidant and anti-inflammatory properties.
Side Effects, Warnings, and Interactions
Compared to many natural remedies, Hypericum perforatumis rife with side effects, warnings, and drug interactions.
Here is what you need to know to determine if Hypericum perforatumis safe for you and whether its downside outweighs its potential benefits.
Side Effects
One of the main reasons people want to try Hypericum perforatum, 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.
Other reported side effects include headache, fatigue, mental confusion, dry mouth, diarrhea, constipation, and stomach pain.
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.
Caution: If you take St. John’s wort, it’s critical that you protect your eyes from sunlight.
Drug Interactions
Hypericum perforatum is known to interact with over 500 medications.
Sometimes, taking Hypericum perforatumis 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.
Women must be aware that St. John’s wort can cause their birth control pills to stop working.
St. John’s wort should be avoided by women who are pregnant or breastfeeding.
You might be tempted to use St. John’s wort to taper off your antidepressant, but mixing the two should never be done.
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 grapefruit or grapefruit juice should not be taken with many medications.
St. John’s wort, much like grapefruit, interferes with drugs by affecting the activity of certain enzymes.
Lastly, do not take it if you have schizophrenia or bipolar disorder as it can trigger episodes of mania.
Caution: If you take any medications, you should not take St. John’s wort until you’ve talked to your doctor or pharmacist.
Food Reactions
Some people experience reactions with St. John’s wort when eating foods high in the amino acid tyramine.
Foods highest in tyramine include those that have been pickled, aged, smoked, or fermented.
This includes beer and wine, many kinds of cheese, aged or cured meat, sauerkraut, fermented soy products, and chocolate.
The combination of tyramine-rich foods and St. John’s wort is especially dangerous for anyone with high blood pressure.
It’s also advisable to avoid alcohol and minimize caffeine intake when supplementing with St. John’s wort.
Unless you are willing to forgo tyramine-rich foods, caffeine, and alcohol, you should steer clear of St. John’s wort supplements.
Interactions With Supplements
St. John’s wort does not safely mix with many other natural supplements.
One should avoid taking St. John’s wort 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:
- ashwagandha
- capsicum
- German chamomile
- goldenseal
- gotu kola
- hops
- kava
- lemon balm
- sage
- scullcap
- Siberian ginseng
- stinging nettle
- valerian
- yerba mansa
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 standardize to contain 0.3% hypericin.
Others will contain dried flowers and leaves of the St. John’s wort plant.
Here’s a typical St. John’s wort supplement label:

The first ingredient is the standardized hypericin extract.
The second ingredient consists of 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.
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, discovered first and studied longer, is a more stable compound than hyperforin.
However, one patented brand of hyperforin, Perika® (WS 5570), utilizes a stabilizing technology.
Germany uses the same form, considering St. John’s wort to have substantial medicinal value.
The only readily available supplements 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.
The independent watchdog group ConsumerLab.com found that sixty percent of the tested St. John’s wort supplements did not contain what the labels stated.
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 – 400 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.
Be patient when trying St. John’s wort.
It can take a few weeks to notice any improvement in depression symptoms.
However, if you do not experience any positive effects in 4 to 6 weeks, medical advice recommends stopping its use.
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, there are many natural antidepressant alternatives.
You can also use proven antidepressant activities such as yoga, breathing exercises, neurofeedback, or mindfulness meditation.
Recommended: Upgrading brain health is key to making your brain work better.
Brain supplement can help you:
- Improve your mental clarity and focus.
- Boost your memory and your ability to learn.
- Increase your capacity to think critically, solve problems, and make decisions.
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Also read our blog on What You Might Not Know About Panax Ginseng