Most prescription antidepressants work by increasing the effects of serotonin. This can be done in different ways. The supplement, Hydroxytryptophan (5-HTP) also works by increasing the effects of serotonin.
5-HTP is isolated for commercial use from a plant. Griffonia simplicifolia is a shrub from west Africa that is used to treat various ailments. The seeds are flat black discs that look like giant lentils. We now know that the seeds contain 5-HTP.
Mechanism of action:
The mechanism of how this works for depression is by increasing the production of serotonin. 5-HTP gives the body the building blocks for serotonin and the body does the rest. The entire pathway starts with L-tryptophan. This is an essential amino acid. An essential amino acid means that the body cannot make it and it needs to be obtained from the diet. Your body then converts L-tryptophan into 5-HTP which then is converted into serotonin. By giving 5-HTP, the body is able to make more serotonin and serotonin can bind to receptors and hopefully lead to decreases in depression.
Why don’t we just give serotonin to increase serotonin levels? Serotonin cannot cross the blood-brain barrier. The blood-brain barrier is a selectively permeable barrier that only allows certain materials to cross into the brain. 5-HTP is able to cross and then can be made into serotonin.
The general dosing for depression is 150-800mg daily for 2-6 weeks. Doses of 400mg daily have been used for up to one year. Dosing of up to 3g daily has been used for a shorter period of time.
(1) A study out of India compared 5-HTP to the prescription antidepressant, Fluoxetine. 60 patients with a first episode of depression were included in the study. The 5-HTP group started with 50mg three times daily and then increased to 100mg three times daily after the first two weeks. The dose was increased one more time to a total daily dose of 400mg in three divided doses after the 4th week. The fluoxetine group had a similar dose titration. These patients started on 20mg for 2 weeks, then 30mg after the second week and then finally 40mg after the 4th week. Placebo pills were given to the fluoxetine group to match the 5-HTP group because fluoxetine is generally given once daily.
Response was defined as a 50% or more reduction in the HAM-D depression scale. 73% of the 5-HTP group responded as compared to 80% of the Fluoxetine group
(2) A meta-analysis was conducted to review tryptophan and 5-HTP for depression. 108 trials were found, but only 2 were high enough quality to meet the criteria for the review. The evidence did seem to show that these substances were better than placebo at treating depression, but due to the quality of the trials, the evidence was deemed insufficient.
5-HTP is possibly safe when used orally and appropriately. There are some concerns that 5-HTP may cause eosinophilia-myalgia syndrome (EMS). EMS is an incurable and sometimes fatal neurological condition. We do not know if a contaminate in 5-HTP caused this reaction or if it is 5-HTP itself. We believe that the side effect was due to a contaminated batch because all of the issues came from a single over-the-counter manufacturer.
1. Antidepressant medications: 5-HTP is a precursor to serotonin and should not be used with prescription antidepressants because most also work on serotonin. This can lead to serotonin syndrome which is characterized by agitation, tremors, anxiety, tachycardia, shivering and sweating.
2. Carbidopa: Carbidopa decreases the peripheral metabolism of 5-HTP and can increase the amount the reaches the brain
3. CNS depressants: 5-HTP can further increase sedation which can cause falls or other safety concerns
5-HTP is generally well tolerated. It can cause nausea, vomiting, abdominal or epigastric pain, diarrhea, and anorexia. There is also a controversy about whether 5-HTP can cause a very serious and potentially fatal side effect called eosinophilia-myalgia syndrome (EMS).
5-HTP may deplete dopamine over time (which would be bad for depression). The body balances the precursors of serotonin and dopamine. Administering more of one of the precursors can deplete the others over time.
Additionally, serotonin is a precursor for melatonin. Melatonin is a sleep hormone. Therefore, 5-HTP administration can increase melatonin levels and cause drowsiness.
I started with 100mg daily on an empty stomach. The capsules are average-sized and filled with a white powder that has cracks in it like desert sand. There is a subtle smell that is hard to describe. It is not good nor bad. I didn’t notice any immediate effect after taking the pill.
My dreams were much more vivid the very first night. Vivid dreams can be caused by prescription antidepressant medications, so this was not that abnormal. I had the strongest reaction on the third night. I remember waking up in the middle of the night thinking that I just had a really profound thought from my dream… and then I promptly forgot what the dream was. I woke up a little while later and thought that my cat was rabbit kicking like he does when he catches his toy. I looked down at him and his ears were quickly scanning back and forth like a satellite. I reached down to check on him and didn’t notice any more movement. I am unsure if I imagined the entire thing or if I was in a half-sleep stupor. It was odd but I was finally able to sleep through the night afterward.
I then noticed some changes in attention and focus. I felt spacey like I hadn’t done anything at work but when I reflected back, I had actually completed a lot of work. It felt like I was not concentrating as well as I normally do. I had severe decreases in energy and I was hitting snooze over and over. I truly could not get out of bed in the morning. It was not all bad though. I did notice some benefits 10 days after starting 5-HTP. Anxiety, second-guessing myself and overthinking had all improved.
I increased the dose to 100mg three times daily after one month. I wanted to see if pushing the dose would be more beneficial. I was on the higher dose for 2 weeks. I was irritable and I skipped going to the gym every day. I set my alarm with a ton of reminders but I could not find the motivation to wake up. I turned the alarms off and sleep until I was almost late to work every day.
After stopping the product, my energy levels quickly returned back to normal. It was an interesting experience due to the vivid, wild dreams, but the sedation was too much for me.
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1. 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.
2. Shaw, K. A., Turner, J., & Del Mar, C. (2002). Tryptophan and 5-Hydroxytryptophan for depression. Cochrane Database of Systematic Reviews.