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st john's wort depression, st john's wort anxiety, st john's wort side effects, 5 htp, what is 5 htp, 5 htp benefits, 5 htp anxiety, 5 htp for depression, 5 htp sleep, 5 htp serotonin

5-htp, Antidepressants & St John's Wort - do they work?

Published Sep 7, 2017 | Updated Jul 22, 2024
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For those seeking an alternative to antidepressants along your quest, you may have encountered 2 supplements - 5-htp and St John’s Wort. How do these two natural supplements stack up against antidepressants and each other? Exciting research shows promise for 5-htp; this over-the-counter supplement works similarly to prescription antidepressants by increasing serotonin levels in the brain. 5-htp can save you from the side effects of medication and another herbal remedy called St John's Wort while still providing you with a natural option. Here’s how serotonin works and how increasing its intake could give that much-needed mood boost you’ve been looking for, bringing sunshine back into your lives.

What vitamin is a natural antidepressant?

A natural isolated nutrient, 5-htp is often praised for its serotonin-boosting properties leading to it being dubbed a "natural antidepressant" on forums and social media sites alike. It’s the building block of your feel-good chemical serotonin (5-ht). It’s found in certain seeds, honey and mushrooms in very small amounts, therefore it’s challenging to get enough of it through your diet[1 Trusted Source 2022 - Foods Research evaluation Edible Mushrooms as a Potential Component of Dietary Interventions for Major Depressive Disorder , [2 Trusted Source 2021 - International Journal of Molecular Sciences Research evaluation 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology , [3 Trusted Source 2013 - Mycoscience 3rd-party resource Levels of physiologically active indole derivatives in the fruiting bodies of some edible mushrooms (Basidiomycota) before and after thermal processing , [4 Trusted Source 2022 - Melatonin Research 3rd-party resource Serotonin, melatonin and their precursors and metabolites and vitamin D3 derivatives in honey , [5 Trusted Source 2022 - International journal of tryptophan research Research evaluation Tryptophan and Biogenic Amines in the Differentiation and Quality of Honey , [6 Trusted Source 2022 - Examine Research evaluation Griffonia Simplicifolia , [7 Trusted Source 2017 - Graduate School-New Brunswick Rutgers, The State University of New Jersey 3rd-party source A phytochemical exploration of Griffonia simplicifolia seeds and leaves . People looking for a natural boost in their mood may opt for a serotonin supplement. Let’s take a look at how 5-htp works its magic.

st john's wort depression, st john's wort anxiety, st john's wort side effects, 5 htp, what is 5 htp, 5 htp benefits, 5 htp anxiety, 5 htp for depression, 5 htp sleep, 5 htp serotonin

What is 5-htp and how does it work?

Due to 5-htp's conversion into the mood-boosting serotonin, research has explored its use for a wide range of conditions including anxiety, sleep disorders, PMS, stress depression and fibromyalgia. 5-htp is a compound converted from a nutrient called tryptophan to form serotonin[8 Trusted Source 1998 - A Journal of Clinical Therapeutic Research evaluation 5-Hydroxytryptophan: a clinically-effective serotonin precursor . This feel-good chemical is a recognised brain messenger that is present all over the brain, particularly in the component of the brain that plays a key role in emotion, the amygdala[9 Trusted Source 2017 - The Journal of Neuroscience Animal study Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission . Low serotonin levels have been connected to depression, mood disorders, the regulation of sleep, anxiety and pain sensation, among other conditions[10 Trusted Source 2009 - Neuropsychiatric Disease and Treatment Research evaluation Both stimulatory and inhibitory effects of dietary 5-hydroxytryptophan and tyrosine are found on urinary excretion of serotonin and dopamine in a large human population . Some studies suggest that certain nutrients and building blocks to serotonin, such as 5-htp, are effective in treating many of these conditions[11 Trusted Source 2017 - International Pharmacopsychiatry Human study 5-Hydroxytryptophan (5-HTP) and a MAOI (Nialamide) in the Treatment of Depressions .

Is 5-htp like Prozac? 

5-htp and antidepressants differ in the way they affect your body. The usual and most well–known way of treating depression is with antidepressants, like Prozac or Zoloft. Prescription medications for depression aim to correct chemical imbalances such as low levels of serotonin in the brain. They can stop the mood-boosting chemical from being re-used for brain processes once it’s produced in the brain, giving serotonin a chance to be released, and also boost the production of the happiness hormone itself[12 Trusted Source 2020 - Personalized Medicine in Psychiatry Human study An updated classification of antidepressants: A proposal to simplify treatment . Research has shown 5-htp’s promising results with some experiencing progress in mental health as soon as after just 1 week of supplementation[13 Trusted Source 1978 - Folia Psychiatrica Et Neurologica Japonica Human study Clinical evaluation of 5-hydroxy-L-tryptophan as an antidepressant drug . 5-htp elevates serotonin levels quicker compared to most antidepressants which take anywhere from a couple of weeks to a month to kick in. This faster response time makes 5-htp appealing to those seeking relief. As an over-the-counter natural supplement, 5-htp is also easy to obtain without a prescription. This gives people more autonomy and ensures a possible natural remedy even for those preferring alternative ways of treating low mood. Additionally, antidepressants are also known for various side effects. Let’s take a look at what they are.

Side effects of antidepressants

While effective, antidepressants give you side effects influencing sleep quality, drowsiness and libido[14 Trusted Source 2021 - NHS 3rd-party source Side effects - Selective serotonin reuptake inhibitors (SSRIs) . The evidence from multiple studies shows that antidepressants can also increase the risk of suicidal thoughts and behaviours in some populations[15 Trusted Source 2016 - Journal of the Royal Society of Medicine Systematic and meta-analysis Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers . The US Food and Drug Administration (FDA) even issued a so-called “black box” warning in 2004 about the increased risk in children, adolescents and young adults up to age 24[16 Trusted Source 2019 - Frontiers in Psychiatry Human study The FDA “Black Box” Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefits? . Assessing true impact is complex and more research is needed given the public health implications[17 Trusted Source 2021 - Cochrane Database of Systematic Reviews Systematic and meta-analysis New generation antidepressants for depression in children and adolescents: a network meta‐analysis . In contrast, 5-htp rarely causes significant side effects. 400 mg has been proven safe when taken for up to a year[18 Trusted Source WebMD 3rd-party source 5-Htp - Uses, Side Effects, and More .

Why you can't take 5-htp with antidepressants?

In short, too much serotonin can harm you. 5-htp & depression and their relationship have been researched quite a lot. Even though the results of an efficacy study of 5-htp in combination with an antidepressant showed promising results for the mental health of participants, you need to be aware of how to take 5-htp[19 Trusted Source 2013 - Asian Journal of Psychiatry Human study Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode . Antidepressants boost your feel-good chemical serotonin. Because 5-htp does the same, taking them together would result in a condition called serotonin syndrome which can cause restlessness, fast heartbeat, hallucinations and an increased body temperature[20 Trusted Source 2023 - StatPearls 3rd-party source Serotonin Syndrome .

How much 5-htp can I take for depression?

5-htp is yet to be recognized as an official treatment for depression by the NHS. More studies need to confirm its impact first. Some studies measured the efficacy of 5-htp for depression in a hope to  establish a better understanding. For example, a study on 60 people who were experiencing their first depressive episode found 5-htp as effective for treating depression as an antidepressant called fluoxetine[19 Trusted Source 2013 - Asian Journal of Psychiatry Human study Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode . They also confirmed that a 5-htp dose of up to 400mg per day is safe even if taken for longer periods. Results of a literature review examining 13 studies on 5-htp & depression showed that safe dosage used in studies varied from 150 mg to 3250 mg per day[21 Trusted Source 2020 - Nutrition Reviews Systematic and meta-analysis Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis .  

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Is St John's Wort or 5-htp better?

Another one of the natural alternative remedies for depression is St John's Wort. 5-htp benefits are scientifically proven while St John’s Wort’s are still up for debate. Benefits of the plant are yet to be properly researched and still, St John’s Wort and depression are often frequently talked about. The plant has been a popular folk remedy for various mental health conditions for centuries. Why is St John’s Wort considered so healthy? It contains an active ingredient called hyperforin which affects your feel-good hormone serotonin and the brain’s relaxation chemical called GABA[22 Trusted Source 2022 - Naunyn-Schmiedeberg's Archives of Pharmacology Research evaluation St. Johnʼs wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems? , [23 Trusted Source 2022 - Cureus Systematic and meta-analysis Advantages and Disadvantages of Using St. John's Wort as a Treatment for Depression . That’s why St John’s Wort and anxiety have also been researched. Here’s how it works compared to the well-known 5-htp.

5-htp vs St John's Wort 

There’s a lack of evidence about whether exactly St John’s Wort works as an antidepressant and even as a supplement. Hyperforin helps keep levels of feel-good brain chemicals like norepinephrine, serotonin and dopamine higher in the brain[22 Trusted Source 2022 - Naunyn-Schmiedeberg's Archives of Pharmacology Research evaluation St. Johnʼs wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems? , [23 Trusted Source 2022 - Cureus Systematic and meta-analysis Advantages and Disadvantages of Using St. John's Wort as a Treatment for Depression . It does this by slowing down the process that normally absorbs these brain chemicals back into brain cells after they are used[22 Trusted Source 2022 - Naunyn-Schmiedeberg's Archives of Pharmacology Research evaluation St. Johnʼs wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems? , [23 Trusted Source 2022 - Cureus Systematic and meta-analysis Advantages and Disadvantages of Using St. John's Wort as a Treatment for Depression . This leaves more of the chemicals available in the spaces between cells, where they can continue to work to improve mood and emotions. St John’s Wort also keeps the GABA levels stable, which helps reduce stress and anxiety[23 Trusted Source 2022 - Cureus Systematic and meta-analysis Advantages and Disadvantages of Using St. John's Wort as a Treatment for Depression . 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. While both 5-htp and St John’s Wort are used as natural remedies for depression by some people, they are yet to be cleared in larger markets. In fact, St John’s Wort's side effects combined with the lack of evidence for the plant's positive impact means the American Food and Drug Administration (FDA) has denied the plant’s products to be licensed for prescription or over-the-counter treatments[24 Trusted Source 2017 - Medical News Today 3rd-party source St. John's Wort: Should I use it? .

St John’s Wort side effects

There are other important considerations for those interested in this natural supplement. Regardless of how big or small the St John’s Wort dosage is, there may be serious side effects[25 Trusted Source 2021 - Medicinal Herbs and Fungi: Neurotoxicity vs. Neuroprotection Research evaluation St. John’s Wort: A Therapeutic Herb to Be Cautioned for Its Potential Neurotoxic Effects and Major Drug Interactions . It reportedly reacts with over 800 medications[26 Trusted Source 2017 - Be Brain Fit 3rd-party source Benefits (and Risks) of St. John's Wort for Depression . 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 required an emergency room visit[27 Trusted Source 2000 - Pharmacotherapy Human study Consumer use of St. John's wort: a survey on effectiveness, safety, and tolerability . For this reason, it is important to discuss with your doctor or pharmacist before you start any supplements.

If you’re looking for a safe, scientifically-backed way to boost your serotonin levels, opt for 5-htp, the natural feel-good chemical booster.

 

References

[1] Fijałkowska, A., Jędrejko, K., Sułkowska-Ziaja, K., Ziaja, M., Kała, K., & Muszyńska, B. (2022). Edible Mushrooms as a Potential Component of Dietary Interventions for Major Depressive Disorder. Foods, 11(10), Article 10. https://doi.org/10.3390/foods11101489

[2] Maffei, M. E. (2021). 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology. International Journal of Molecular Sciences, 22(1), Article 1. https://doi.org/10.3390/ijms22010181

[3] Muszyńska, B., Sułkowska-Ziaja, K., & Wójcik, A. (2013). Levels of physiologically active indole derivatives in the fruiting bodies of some edible mushrooms (Basidiomycota) before and after thermal processing. Mycoscience, 54(5), 321–326. https://doi.org/10.1016/j.myc.2012.11.002

[4] Kim, T.-K., Fabisiak, A., Brzeminski, P., Reiter, R. J., & Slominski, A. T. (2022). Serotonin, melatonin and their precursors and metabolites and vitamin D3 derivatives in honey. Melatonin Research, 5(3), 374–380.  https://doi.org/10.32794/mr112500137

[5] Borges, C. V., Nunes, A., Costa, V. E., Orsi, R. de O., Basilio, L. S. P., Monteiro, G. C., Maraschin, M., & Lima, G. P. P. (2022). Tryptophan and Biogenic Amines in the Differentiation and Quality of Honey. International Journal of Tryptophan Research, 15https://doi.org/10.1177/11786469221102098.

[6] Patel, K. (2022). Griffonia Simplicifolia. Examine. https://examine.com/supplements/griffonia-simplicifolia/

[7] Giurleo, D. (2017). A phytochemical exploration of Griffonia simplicifolia seeds and leaves [Master Thesis]. Graduate School-New Brunswick Rutgers, The State University of New Jersey. https://doi.org/doi:10.7282/T3NC63NT

[8] Birdsall, T. C. (1998). 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Alternative Medicine Review: A Journal of Clinical Therapeutic, 3(4), 271–280. https://pubmed.ncbi.nlm.nih.gov/9727088/

[9] Sengupta, A., Bocchio, M., Bannerman, D. M., Sharp, T., & Capogna, M. (2017). Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission. The Journal of Neuroscience, 37(7), 1785–1796. https://doi.org/10.1523/JNEUROSCI.2238-16.2016

[10] Trachte, G., Uncini, T., & Hinz, M. (2009). Both stimulatory and inhibitory effects of dietary 5-hydroxytryptophan and tyrosine are found on urinary excretion of serotonin and dopamine in a large human population. Neuropsychiatric Disease and Treatment, 227. https://doi.org/10.2147/ndt.s5040

[11] López-Ibor Aliño, J. J., Ayuso Gutierrez, J. L., & Montejo Iglesias, M. L. (2017). 5-Hydroxytryptophan (5-HTP) and a MAOI (Nialamide) in the Treatment of Depressions. International Pharmacopsychiatry, 11(1), 8–15. https://doi.org/10.1159/000468207

[12] Alvano, S. A., & Zieher, L. M. (2020). An updated classification of antidepressants: A proposal to simplify treatment. Personalized Medicine in Psychiatry, 19–20, 100042. https://doi.org/10.1016/j.pmip.2019.04.002

[13]  Nakajima, T., Kudo, Y., & Kaneko, Z. (1978). Clinical evaluation of 5-hydroxy-L-tryptophan as an antidepressant drug. Folia Psychiatrica Et Neurologica Japonica, 32(2), 223–230. https://doi.org/10.1111/j.1440-1819.1978.tb00143.x

[14] Side effects - Selective serotonin reuptake inhibitors (SSRIs) (2021). NHS. https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/ssri-antidepressants/side-effects/

[15] Bielefeldt, A. Ø., Danborg, P. B., & Gøtzsche, P. C. (2016). Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers. Journal of the Royal Society of Medicine, 109(10), 381–392. https://doi.org/10.1177/0141076816666805

[16] Fornaro, M., Anastasia, A., Valchera, A., Carano, A., Orsolini, L., Vellante, F., Rapini, G., Olivieri, L., Di Natale, S., Perna, G., Martinotti, G., Di Giannantonio, M., & De Berardis, D. (2019). The FDA “Black Box” Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefits? Frontiers in Psychiatry, 10, 294. https://doi.org/10.3389/fpsyt.2019.00294

[17] Hetrick, S. E., McKenzie, J. E., Bailey, A. P., Sharma, V., Moller, C. I., Badcock, P. B., Cox, G. R., Merry, S. N., & Meader, N. (2021). New generation antidepressants for depression in children and adolescents: a network meta‐analysis. Cochrane Database of Systematic Reviews, 5https://doi.org/10.1002/14651858.CD013674.pub2

[18] 5-Htp - Uses, Side Effects, and More (n.d.). WebMD. https://www.webmd.com/vitamins/ai/ingredientmono-794/5-htp

[19] Jangid, P., Malik, P., Singh, P., Sharma, M., & Gulia, A. kumar D. (2013). Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian Journal of Psychiatry, 6(1), 29–34. https://doi.org/10.1016/j.ajp.2012.05.011

[20] Simon, L.V., & Keenaghan, M. (2023). Serotonin Syndrome. https://www.ncbi.nlm.nih.gov/books/NBK482377/

[21] Javelle, F., Lampit, A., Bloch, W., Häussermann, P., Johnson, S. L., & Zimmer, P. (2020). Effects of 5-hydroxytryptophan on distinct types of depression: a systematic review and meta-analysis. Nutrition Reviews, 78(1), 77–88. https://doi.org/10.1093/nutrit/nuz039

[22] Kholghi, G., Arjmandi-Rad, S., Zarrindast, M.-R., & Vaseghi, S. (2022). St. Johnʼs wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems? Naunyn-Schmiedeberg’s Archives of Pharmacology, 395(6), 629–642. https://doi.org/10.1007/s00210-022-02229-z

[23] Canenguez Benitez, J., Hernandez, T., Sundararajan, R., Sarwar, S., Arriaga, A., Khan, A., Matayoshi, A., Quintanilla, H., Kochhar, H., Alam, M., Mago, A., Hans, A., & Benitez, G. (2022). Advantages and Disadvantages of Using St. John’s Wort as a Treatment for Depression. Cureus, 14(9), 29468. https://doi.org/10.7759/cureus.29468

[24] Nordqvist, C. (2017). St. John's Wort: Should I use it? Medical News Today. http://www.medicalnewstoday.com/articles/174928.php

[25] Fujihashi, A., Ramesh, S., Govindarajulu, M., Almaghrabi, M., Nadar, R. M., Deruiter, J., Moore, T., Pondugula, S., Agrawal, D. C., & Dhanasekaran, M. (2021). St. John’s Wort: A Therapeutic Herb to Be Cautioned for Its Potential Neurotoxic Effects and Major Drug Interactions. In D. C. Agrawal & M. Dhanasekaran (Eds.), Medicinal Herbs and Fungi: Neurotoxicity vs. Neuroprotection (pp. 369–389). Springer. https://doi.org/10.1007/978-981-33-4141-8_15

[26] Alban, D. (2017). Benefits (and Risks) of St. John's Wort for Depression. Be Brain Fit. https://bebrainfit.com/st-johns-wort-benefits-depression

[27] Beckman, S. E., Sommi, R. W., & Switzer, J. (2000). Consumer use of St. John’s wort: a survey on effectiveness, safety, and tolerability. Pharmacotherapy, 20(5), 568–574. https://doi.org/10.1592/phco.20.6.568.35152

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