St John’s Wort for depression

As part of my effort to summarise the clinical evidence for certain herbs that have been researched more than others, I want to start with St John’s Wort as it’s rather a celebrity of the plant world.

I also want to add some background as, although the clinical evidence is valuable, the authors of the scientific papers are seldom herbalists.

St John’s Wort (Hypericum perforatum)

Hypericum has been used for centuries for a number of different indications, and is very much a native British herb. Herbalists use it in gastrointestinal disorders as an anti-inflammatory, conditions involving nerve damage such as herpes and multiple sclerosis, and externally as a poultice or oil to help heal wounds, soothe sprains and other injuries.

It is also commonly used as a ‘nervine’ to ease anxiety and depression, and in recent times its reputation as a safe and effective mood-enhancer has grown considerably due to the huge number of clinical trials conducted on the subject.

The depressing facts

The World Health Organisation (WHO) predicts that by 2020, depression will be the second leading cause of disability worldwide. It has been shown by work in Indian and African communities that depression affects the populations of developing countries equally – it is not just an affliction of stressful modern societies.

Furthermore, research into the underlying disease process has uncovered much more than the ‘chemical imbalance’ of neurotransmitters often thought of as the main factor in depression. Stress, physical disease and allergy have all been linked to core inflammatory processes that may play a role in the development of mental and neurological illness.

So what can humble Hypericum do about this globe-spanning mental health catastrophe?

The research

Well, it has been deemed a possible safe alternative to conventional SSRIs (selective serotonin re-uptake inhibitors) and ‘tricyclic’ antidepressants, whose side effects often outweigh their benefits.

It was found that the difference in effect between placebo and these drugs was only significant when the patient was very severely depressed – and this was attributed to a decreased response to placebo rather than an increased response to the drug. It has also been suggested that many more of the positive trials get published than the negative ones – called ‘publication bias’.

Trials of Hypericum began in the 1980s to investigate an alternative and, from 1995–2009, three Cochrane reviews have summarised the results of the many trials. Cochrane reviews are considered the ‘gold standard’ in medical research and are intended to pool all the results from the highest quality clinical trials.

The Hype About Hypericum

One of the early reviews looked at 27 trials with a total of 2291 patients, all with ‘neurotic depression’ or ‘mild-moderate severe depressive disorder’. They concluded that Hypericum was more effective than placebo but, although patients reported fewer side effects than those taking the conventional medication (26.3% compared to 44.7%), they could not determine whether Hypericum was as effective as standard anti-depressants.

A further review detailed some recent, well-conducted trials suggesting Hypericum didn’t actually show any improvement above placebo. They also saw that the efficacy of Hypericum depended on the size and setting of the trial. Those most likely to show a benefit over placebo were small, included only patients with mild depressive symptoms and were conducted in German-speaking countries.

It was around this time that St. John’s Wort was also found to speed up the enzyme systems processing various drugs in the body (the Pill, HIV medication, immunosuppressant drugs, digoxin) making them dangerously less effective. For a while, the hype surrounding Hypericum became tarnished by scientific discovery, and herbalists around the world hung their heads in disappointment as hopes of world peace slipped silently away.

However, since results seemed less pronounced in patients with major depression, an update of the 2005 paper limited the trials to patients with only major depression. Twenty-nine trials with a total of 5489 patients were analysed and it was shown that Hypericum was more effective than placebo as well as being similarly effective to standard anti-depressants, with fewer side effects.

Variations in results

Trials from German-speaking countries still seemed to be more favourable – possibly because Hypericum is widely prescribed by physicians in these countries for depression and anxiety. This may mean the health professionals were biased – but it is equally likely that their experience led them to choose slightly different types of participants for the studies, despite the criteria.

It is clear from studies of patients with more severe depression that Hypericum works differently in different groups of people, and it may be particularly suited to people with atypical depressions such as SAD and physical symptoms of depression like fatigue and irritable bowel syndrome (IBS).

The composition of herbal extracts also varies hugely according to climate, soil type, methods of harvesting, processing and packaging, and shelf life of the final product. The findings of the 2009 review apply to extracts of 500-1200mg/day, using 50-60% ethanol for extraction. Most Hypericum tinctures used by herbalists are made with 45% alcohol, but we often prescribe more than 1200mg/day, so perhaps this cancels things out!


Interestingly, levels of the compound hypericin (blamed for the enzyme interactions above) have been shown to be much lower in tincture than in tablets, capsules or infusions (teas). This may explain why herbalists have good results with Hypericum tincture in patients who want to wean themselves off conventional anti-depressants.

However, initial research suggested it was hypericin that was responsible for the anti-depressant effects of St. John’s Wort and many manufacturers started producing tinctures with added hypericin. Now we know that it is a combination of various compounds in the herb that produces the benefits. So if I may give any advice to readers, it’s:

  1. Don’t buy Hypericum products that have added hypericin…


  1. Always consult a medical herbalist before taking any Hypericum extract.

So What Does it all mean?

Hypericum is a valuable herb and more than just an anti-depressant but, with the evidence behind us, we can say it really works in both mild-moderate severe depression and major depression as well as in people with atypical depressive symptoms.

You don’t have to be severely depressed in order to take Hypericum, but if you are, and you’re not happy with conventional medication for any reason, it may provide a safe and effective alternative. And that’s good news.


5 thoughts on “St John’s Wort for depression

  1. Do we know if the method of extraction keeps the beneficial metabolites of Hypericum active or if temperature during storage has an effect?

    It’s the packaging and shelf life that always makes me suspicious of herbs, herbal extracts, and such, especially when they’re just setting on the shelf in a store at room temperature. And they’re not regulated at all, at least in the US. I’m not sure how labeling and regulations are different between the US and England, but is there a general rule to follow when buying these things over the counter? In the US, I’ve been told to look for “United States Pharmacopeia” -USP certified on the label, which means the product has meant whatever guidelines that have been set by the USP to ensure the best quality end product. But more often what I see is something like “quality verified by independent lab tests” which sounds like nothing more than a string of words the company slapped on the label to make the product sound more legitimate.


    1. Indeed – apparently hyperforin is best extracted in n-hexane and hypericin in ethanol, with other factors like temperature, time of extraction and number of extractions also affecting the overall result. The higher the temperature, the better, it seems.

      However, herbal tinctures are not prepared like this and the variation in hyperforin and hypericin content between different brands of tincture is likely to be large. It will again depend on other things like climate and soil composition. Wild herbs are said to contain more of these ‘secondary metabolites’ we use as medicine as they are produced by the plant itself for survival/defence reasons. Also, hypericin and pseudohypericin are both relatively unstable compounds affected by light and temperature. This is another reason why it is unclear whether the negative effects of hypericin (induction of CYP450 enzymes) apply to whole herbal tinctures that have been sitting on the shelf for a while. You’re right about herbal products being on shelves at room temperature – which is why herbalists keep their tinctures in cold rooms.

      However, the main issue here is that we don’t know how much hypericin/ pseudohypericin/hyperforin contribute to the overall effect of Hypericum and how many other compounds are involved. You’ve hit the nail on the head re: regulation – but it is difficult to regulate a product that is not standardised, and even more difficult to standardise a product that is so variable. It has been shown on various occasions that whole herbal extracts work better than their individual compounds, and often it is unclear why. These apparently ‘synergistic’ interactions form the basis of herbal pharmacology. In this month’s HOTM I will be writing about a specific and fascinating synergistic mechanism of the native British herb Barberry, so keep reading!

      Meanwhile, I understand your frustration with commercial herbal products and can only advise you to consult your nearest herbalist. I don’t know how US herbalists source their herbs but UK practitioners buy wholesale from reputable suppliers with Traditional Herbal Registration (THR) certificates. Mediherb products are the closest you can get to worldwide, quality, standardised herbal medicines, but registration is only open to health professionals.

      I hope this answers your question! As always, thanks for the feedback.


      1. Something like curcumin could potentially suppress, or counteract the effect of hypericin while enhancing the other active compounds because it suppresses Cyp450 while activating phase II detox enzymes. Curcumin has been found to increase the bioavailability of certain drugs through this mechanism….but then you need something like piperidine to increase the bioavailability of curcumin.

        I’ll have to look into herbalism in the US because you have me curious now. Almost all alternative forms of medicine that I’ve encountered lie somewhere in the realm of pseudoscience/homeopathy. So I tend to be overly skeptical when I see “natural” and “alternative” in a description because usually science is never correctly applied to these things, and I wish it wasn’t that way. There is a focus on naturally occuring compounds here but it is centered around Universities and a curriculum of biology/chemistry. However, there is very little exposure to herbs in general unless you study them specifically as a scientist. I don’t know what an herbalist education would you get you here in the US, but on the surface is seems like the UK may have a better grasp on the topic (or I’m just speaking completely from ignorance), but I really like your approach in that it’s scientific and realistic. It’s eye opening and refreshing to see! I look forward to future posts 🙂


  2. You’re exactly right when you say that science is not “correctly” applied to alternative approaches. The randomised controlled trial is a difficult method through which to examine the effects of medicines that are so highly variable in nature – ie. there’s inevitably only so much you can ‘control’. Plus, herbalists almost never prescribe one herb only – they will usually combine 4,5, up to 7 or 8 herbs in a prescription and Chinese preparations often contain more than 10. So the point you make about turmeric (or curcumin) is very relevant in that most herbs will be acting alongside others in a prescription and possibly having effects that would be incredibly difficult to pin down and analyse, considering the number of constituents and therefore potential interactions in each one.

    I’m very pleased to have sparked your interest in terms of looking up herbalists. The US is actually a great place for herbal medicine, possibly because people are already used to the idea of paying for healthcare! Check out Rosemary Gladstar and Paul Bergner. Julian Barker, a widely respected British herbalist, also began his training in North America, and Lisa Ganora who wrote the herbal bible of phytochemistry ‘Herbal Constituents’ teaches at the Colorado School of Clinical Herbalism. Delve and enjoy! 🙂


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