The St. John's Wort (hypericum perforatum) plant has been a popular folk remedy for a variety of mental health conditions for centuries. Despite this, there isn't a single study with the correct research methodology to support its use.
St John’s Wort tablets or other preparations include small amounts of the active ingredient, hyperforin. This is supposed to work to block the re-uptake of three chemicals found in the brain that regulate mood and emotions; norepinephrine, serotonin, and dopamine.
These are known as neurotransmitters as they help move chemical messages between neurons, or nerve cells, in the brain. It is believed that an imbalance in these chemicals is the basis for depression, anxiety or fatigue in some people. However, despite containing hyperforin, St John's Wort has not been proven effective for treatment of major depression. 
Why doesn’t the science stack up?
The existing evidence, based on studies testing St John's Wort, found no significant effect when used alone. There is also a lack of evidence about whether it works as a supplement.
St John’s Wort depression treatments are used in some European countries but have not been cleared in larger markets like the United States. In fact, St John’s Wort side effects combined with the lack of evidence for the positive impact of the plant, means the American Food and Drug Administration (FDA) has denied the plant’s products to be licensed for either prescription or over the counter treatments. 
What does St John's Wort actually do?
The active ingredient of St John's Wort, Hyperforin is supposed to improve mental health by keeping levels of norepinephrine, serotonin, and dopamine high. It does this by reducing the activity of re-uptake transporters which absorb and recycle neurotransmitters into the brain’s neurons. It also blocks the reabsorption (and so keeps levels stable) of GABA. That’s a neurotransmitter with a positive impact on relaxation and stress levels.
5-hydroxytryptophan, known as 5-HTP, is a natural isolated nutrient which works by converting, upon ingestion, into serotonin (5-ht). That regulates mood and has been shown to be effective as a "natural antidepressant" and "works as well to treat depression as the popular SSRIs Prozac and Zoloft."
What is 5-HTP and how does it work?
Research has suggested that because 5-HTP is a building block of the mood-boosting chemical serotonin it may help with anxiety, sleep disorders, PMS, stress, depression, and fibromyalgia. As an easy comparison between the two St John’s wort claims to stop the reabsorption of serotonin while 5-HTP increases the amount of serotonin overall.
According to research by Birdsall, 5-htp is the transitional metabolite of L-tryptophan (LT), the essential amino acid in the biosynthesis of serotonin . Serotonin, as described by Berumen et al., is a recognised neurotransmitter distributed brain wide with a particular presence in the hippocampus - a major component of the brain . Serotonin levels have been connected to depression, mood disorders, the regulation of sleep, anxiety and pain sensation, among other conditions . Nutrient precursors, such as 5-htp, have been shown to be effective in treating many of these conditions, as well as sharing promise for fibromyalgia and binge eating that is associated with obesity .
5-htp for depression
Research conducted by Nakajima et al., on patients with depression found that those who took 5-htp experienced marked improvements, some of whom noticed excellent progress within just one week . A similar study by Alino et al., also found that patients who took nialamide + 5-htp as opposed to nialamide alone achieved a fuller recovery .
What are the risks of taking St John’s Wort?
There are other important considerations for those interested in natural supplements. Regardless of how big or small the St John’s Wort dosage, there may be serious side effects. It reportedly reacts badly with over 800 medications . The most concerning of these is the risk of compromising birth control medication by taking St John’s wort at the same time. This is because the herb can affect the activity of certain enzymes.
Furthermore, it's been suggested that consumers need higher awareness of taking St John's Wort, as 47% of those undertaking a group trial of St John's Wort to treat depression experienced side effects; one patient consequently requiring an emergency room visit. 
For this reason, it is important to discuss with your doctor or pharmacist before you start any course of supplements.
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