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An Herbal Power Duo for Depression: 5-HTP and St. John's Wort

The complexity of human bodies cannot be understated; the sheer number of chemical reactions that must operate properly every second is almost too much to comprehend. In an attempt to shed light on some of this complex machinery, I want to explore the biochemical importance of one particularly ubiquitous compound: serotonin.

Belonging to the cell class neurotransmitter, serotonin is used to transmit messages between nerve cells. (Think of it almost as the body’s postman, delivering specific messages to specific addresses across the body.) Serotonin is known to affect a whole host of biological processes including mood, anxiety, reward response, eating and sexual behaviour, gastrointestinal motility and sleep. Because of its far-reach, it is important that its presence in the body is regulated. Naturally occurring chemicals derived from plants have given us this ability, as compounds like 5-HTP and herbs like St. John’s Wort have been identified as serotonin powerhouses.

5-Hydroxytryptophan (5-HTP)

Derived from the seeds of the African plant Griffonia simplicifolia, the amino acid 5-HTP is a precursor in the biosynthesis of serotonin. Usually taken in dosages of 50-100 mg/day, it is thought that increasing the amount of 5-HTP in the body results in an increase in serotonin levels, as serotonin is made from 5-HTP.

St. John’s Wort

Found in temperate climates, Hypericum perforatum is a sprawling, leafy herb with black-spotted yellow flowers that has been used for medicinal purposes for millenia. In Ancient Greece, it was common practice for St. John’s Wort (SJW) to be dried and its flowering tops soaked in olive oil, producing a deep red solution. Using this method of extraction, SJW was used to treat wounds, infections, inflammation, melancholy and depression in Ancient Greece throughout the middle ages and into the 18th and 19th centuries.

With technologies available to us today, scientists have been able to understand the biochemistry behind these profound discoveries made thousands of years ago.

Active ingredients: Hypericin and hyperforin

There are many chemical components to SJW that have biochemical implications. Flavonoids found in the flowers and leaves, for example, exhibit antiviral and antioxidant properties that help explain why SJW extracts have been so successful at treating some illnesses. The two chemicals hypericin and hyperforin, however, affect serotonin levels present in the body, offering an explanation for the antidepressant quality of SJW.


In the body, there are a class of enzymes called monoamine oxidase (MAOs) that are involved in the degradation of amine neurotransmitters, like serotonin. When there are excess MAOs present in the body, too much serotonin is degraded, leading to a serotonin deficiency. Starved of serotonin, the body begins to exhibit the symptoms of depression, including malaise, disinterest and sadness.

Hypericin is a naphthodaianthrone compound found in the black dots along the flowers of the SJW plant and is responsible for giving the oil extracts its deep red hue. When hypericin enters the body, it acts as an inhibitor for MAO-A and -B enzymes, which prevents them from breaking down serotonin. With more serotonin freed up, it can more readily produce dopamine and more easily carry out its bodily functions, reducing depression symptoms in most users.


In recent research, it has been found that the phloroglucinol compound, hyperforin, even more so than hypericin, accounts for the therapeutic effects of SJW. Common pharmaceuticals used to treat depression fall in a class called selective serotonin reuptake inhibitors (SSRIs), which effectively block the reabsorption of serotonin by the brain, increasing serotonin levels in the body. Unlike SSRIs, hyperforin inhibits serotonin absorption by elevating intracellular concentrations of specific ions. Because these ions are responsible for regulating serotonin absorption, when the concentration gradient is decreased, the absorption of serotonin is decreased as well. In this way, the levels of serotonin are increased in the body. Because of this process, there is an overall increase in 5-HT receptors as well, offering a potential long-term benefit to using hyperforin as a treatment for depression.

5-HTP and St. John's Wort: An Herbal Power Duo for Depression

When used together, the increase in 5-HTP in the body induced by the supplement combined with the increased number of receptors available for action caused by SJW can increase serotonin levels dramatically. Because of this, these two supplements are often used in conjunction with each other to treat mild and moderate cases of depression.

Considerations for 5-HTP and St. John's Wort

Side-effects from using these compounds include diarrhea, dizziness and nausea, as well as the potential to worsen some existing medical conditions like ADHD, obesity or Parkinson’s. Because of their interaction with cytochrome p450, an enzyme that clears drugs and ingested chemicals from the bloodstream, it is not recommended that these supplements be taken alongside other prescription medications. In clinical studies, these side-effects tended only to occur when used long-term.

As always, this information is intended for educational purposes only and not as medical advice. Please consult your doctor before adding any supplement to your regimen.


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