Table of Contents
5-HTP (5-Hydroxytryptophan or oxitriptan) is an amino acid that is naturally produced in your body. 5-HTP is synthesized from the amino acid tryptophan which we get from food.
5-HTP is the immediate precursor of serotonin. And as a nootropic and dietary supplement, 5-HTP is popular with those who advocate its effectiveness in treating depression. Along with a number of other serotonin-related diseases.
But using 5-HTP for treating depression and anxiety is not supported by science. The research is contrary to how 5-HTP is viewed by many, including medical doctors.
When we dig into the research, we find that 5-HTP may be contraindicated for depression in those whom marketers advocate its use.[i]
We’re all for boosting neurotransmitter levels and optimizing cognitive performance here at Nootropics Expert®. But now and again I run into a nootropic or dietary supplement that may be popular. But also may be a particularly bad idea.
We’re going to get to the bottom of how 5-HTP works in your brain in this review. We’ll examine why it’s critical for brain health. And reasons why you may want to find another way to boost serotonin levels in your brain.
5-HTP helps:
- Anxiety & Depression. 5-HTP is synthesized into serotonin in brain cells. Elevating levels of serotonin can help relieve the symptoms of anxiety and depression.
- Neurotransmitters. 5-HTP is a necessary ingredient for serotonin synthesis which boosts mood and social behavior, improves memory, regulates appetite and digestion, sleep, sexual desire and function.
- Brain Optimization. A critical balance of the primary neurotransmitters serotonin and dopamine are needed for the highly optimized brain. When these neurotransmitters are not in balance it affects mood, memory, cognition, decision-making, sexual desire, and a host of other critical life functions.
Overview
5-HTP (5-Hydroxytryptophan or oxitriptan) is an amino acid that’s synthesized from the essential amino acid tryptophan.
Tryptophan is hydroxylated by tryptophan hydroxylase to 5-HTP (5-hydroxytryptophan), then decarboxylated to serotonin (5-hydroxytryptamine or 5-HT).[ii]
Tryptophan → 5-HTP → serotonin
80-90% of your body’s serotonin is made in your intestines. But serotonin cannot cross the blood-brain barrier. So all the serotonin that your brain needs has to be made within the brain. This is where 5-HTP comes in…
5-HTP crosses the blood-brain barrier more readily than tryptophan. And gets synthesized into serotonin at a faster rate than from tryptophan.[iii]
As a neurotransmitter, serotonin influences directly and indirectly, the majority of brain cells. So if you want to boost serotonin in your brain, some find that supplementing with 5-HTP is better than taking tryptophan.
Tryptophan, which your body uses to make 5-HTP, can be found in turkey, chicken, milk, potatoes, pumpkin, sunflower seeds, turnip and collard greens, and seaweed.
5-HTP as a nootropic supplement is a naturally occurring amino acid derived from seed pods of Griffonia simplicifolia, found in West and Central Africa. 5-HTP content in extracts of this plant vary from 2 – 20.83% (from seeds obtained in Ghana).[iv]
How does 5-HTP work in the Brain?
5-HTP is a precursor to serotonin. The neurotransmitter serotonin plays a role in sleep, appetite, learning & memory, mood, and sexual function.
When tryptophan’s role in converting to 5-HTP for boosting serotonin doesn’t work efficiently, the result is often depression, chronic headache and insomnia.
An open-label trial was conducted in Italy to determine the efficacy of using 5-HTP in young subjects with high levels of “romantic stress”.
Serotonin has been linked to human romantic attachment. So researchers in this study set out to determine brain levels of Brain-Derived Neurotrophic Factor (BDNF) and serotonin in relation to changes in romantic stress during the study.
15 healthy subjects (mean age 23.3 years) who had a “romantic breakup” took part in the study. Participants received 60 mg of Griffonia simplicifolia extract containing 12.8 mg 5-HTP daily for 6 weeks.
The subjects were evaluated for BDNF and serotonin levels at the beginning of the study, at 3 weeks and then again at the end of the 6-week trial.
The scientists observed significant improvements in romantic stress scores from weeks 0 through 3. So far, 5-HTP seems to be working. But no further improvement was seen from weeks 3 through 6. Even though the young people had significantly higher levels of BDNF and serotonin.[v]
More Involved in Depression and Stress than Serotonin
This “romantic breakup” study is a classic illustration of why using 5-HTP alone to treat depression and stress may not work. And if it does work, why it may not work for long.
Depression is often more than simple serotonin dysfunction. Depression can also be associated with catecholamine dysfunction, including dopamine and/or norepinephrine. Or a combination of serotonin and catecholamine dysfunction.
When you take 5-HTP alone, you are also depleting dopamine, norepinephrine, and epinephrine. Synthesis of serotonin from 5-HTP, and dopamine from L-DOPA is catalyzed by the same enzyme, L-aromatic amino acid decarboxylase (AAAD).
Dopamine and serotonin precursor supplementation must be taken in proper balance. Because when you use only 5-HTP, it dominates dopamine at the AAAD enzyme synthesis level.
Blocking dopamine synthesis at the AAAD enzyme through competitive inhibition will lead to depletion of dopamine and the rest of the catecholamines.[vi]
Going back to our Italian study of young people dealing with “romantic stress”, the subjects stopped responding to 5-HTP in the 2nd half of the study. Likely because their catecholamines became depleted through continuous 5-HTP supplementation.
Studies have found that when dopamine is depleted enough, 5-HTP will no longer function.[vii]
Catecholamine Dysfunction Affects More Than Just Depression
When catecholamine neurotransmitter levels (dopamine and/or norepinephrine) influence depression, supplementing with 5-HTP alone is not the way to go. Because you may deplete dopamine and norepinephrine, worsening the disease and its underlying cause.
But this contraindication is not exclusive to depression. It extends to all other diseases where catecholamine dysfunction has been implicated. Including ADHD[viii], obesity, anxiety, seasonal affective disorder (SAD), and Parkinson’s Disease.[ix]
How things go bad
Amino acid precursors of serotonin (i.e. 5-HTP) and dopamine (i.e. L-Tyrosine) work together during synthesis, metabolism and transport to the point that they function as one system.
When serotonin and dopamine are properly balanced, functions that are regulated only by serotonin, can be regulated by manipulating dopamine levels. And functions regulated only by dopamine in this balanced state can be regulated by manipulating serotonin.[x]
When you mess with this balance and improperly supplement with serotonin or dopamine precursors, you don’t get the desired effect of using that nootropic. And you increase the possibility of side effects with too much serotonin.
If you supplement with only one precursor (i.e. 5-HTP to boost serotonin) that dominates the other system (i.e. dopamine synthesis), depletion of the dominated system will occur (i.e. depleted dopamine).
And if this effect is pronounced enough, you will not get the benefit you were aiming for when supplementing with the original precursor (i.e. 5-HTP).
A powerful example of this effect is in the management of Parkinson’s Disease where the effects of L-DOPA are no longer observed over time due to serotonin depletion.[xi]
Since serotonin and dopamine cannot cross the blood-brain barrier, the number of serotonin and dopamine molecules in the brain is a function of the amount of nutrients (amino acid precursors) that are available to be synthesized into new neurotransmitter molecules.
Optimizing brain function with minimal side effects is NOT a function of supplementing until you get sufficiently high amino acid levels. It’s a function of achieving the proper balance between serotonin and dopamine.
5-HTP benefits
5-HTP is absolutely critical for synthesis of serotonin in your brain. But supplementing with 5-HTP to boost serotonin does not work well.
Using 5-HTP to treat depression has had very little success over the last few decades of clinical trials and biohacking.
Integrating 5-HTP into your nootropic stack is much more complicated than simply adding some 5-HTP in order to boost serotonin.
5-HTP alone will not work for depression, or any other issue you’re dealing with involving the catecholamines (dopamine, norepinephrine, epinephrine) because of 5-HTP’s tendency to deplete those neurotransmitters.
5-HTP will boost serotonin in your brain.[xii] But 5-HTP must be carefully stacked with precursors for dopamine and norepinephrine or you risk making the situation worse.
You must avoid supplementing with only one of the serotonin or dopamine amino acid precursors. When amino acid precursors are not in balance, you end up with decreased effectiveness of that nootropic, increased side effects, and depletion of the non-dominant system.
How does 5-HTP feel?
Reactions to supplementing with 5-HTP vary considerably but the one consistent theme is initial feelings of well-being, better sleep, less need for sleep, improved mood, less social anxiety, lower appetite, improved tolerance for stress and improved cognitive function.
And after a couple of weeks of dosing 5-HTP – side effects begin. Serotonin overload results in dopamine and norepinephrine depletion.
Side effects include feelings of lethargy, depression, brain fog, stomach pain, and possibly a chronic tension type of headache. Worst case scenario is nausea, vomiting and even blacking out.
Neurohackers who report consistent success supplementing with 5-HTP stack it with B-Vitamins, a dopamine precursor like L-Tyrosine, and only use 5-HTP as needed.
Those who have a bad experience with 5-HTP from the start often have no idea why they’ve reacted badly. But an educated guess is their depression was catecholamine (dopamine, norepinephrine, epinephrine)-related. And boosting serotonin made their dopamine-related issues worse. Very quickly.
One huge word of WARNING: Do NOT take 5-HTP with any antidepressant medication. You put yourself in the very real danger of Serotonin Syndrome which can ultimately kill you.
5-HTP Clinical Research
5-HTP supplements are heavily marketed as a natural remedy for depression. But the science does not support using 5-HTP for depression. We have decades of clinical trials available. And there is no evidence of the efficacy in using 5-HTP for depression.
5-HTP instead of selective serotonin reuptake inhibitors
The Department of Public Health at the University of Queensland Medical School in Australia did a systematic review of literature dating from 1966 – 2000 for “5-HTP” and “depression”.
The researchers found 108 clinical studies of which only 2 studies, one with serotonin (5-HT) and one with L-Tryptophan for a total of 64 patients met sufficient quality criteria to be included. These studies suggest serotonin (5-HT) and L-Tryptophan are better than placebo at alleviating depression.
But the researchers noted “the small size of the studies, and the large number of inadmissible, poorly executed studies, cast doubt on the results from potential publication bias, and suggests that they are insufficiently evaluated to assess their effectiveness.”[xiii]
5-HTP for Fibromyalgia
A double blind controlled study in Italy studied the efficacy of using 5-HTP in treating fibromyalgia symptoms.
50 patients with primary fibromyalgia syndrome were selected for this study. This 1990 study did not publish the amount of 5-HTP used. But the researchers found a significant improvement in fibromyalgia symptoms with only mild and transient side effects.[xiv]
5-HTP for Treatment of Depression
Insufficient activity of the neurotransmitters serotonin and norepinephrine is a central element of the model of depression most widely held by neurobiologists today.
In the late 1970’s and 1980’s, numerous studies were performed in which depressed patients were treated with the serotonin precursors L-Tryptophan and 5-Hydroxytryptophan (5-HTP), and the dopamine and norepinephrine precursors Tyrosine and L-Phenylalanine.
A summary published in the Alternative Medicine Revue looked at the data from all these studies. The author noted that the nature of the studies makes it difficult to draw firm conclusions regarding the efficacy of neurotransmitter precursors for treating depression.
While there is evidence that precursor loading could work, particularly for serotonin precursor 5-HTP, more studies of suitable design and size “might lead to more conclusive results”.[xv]
Those studies have not materialized since that report was published 22 years ago.
5-HTP Recommended Dosage
Recommended dosage of 5-HTP if you’re going to try it is 50 mg 1 – 3 times per day.
Some studies have used higher doses than the recommended dose, but 5-HTP can be toxic for your central nervous system at high doses.
For anxiety or depression, 5-HTP is dosed at 150 – 300 mg per day total.
To relieve post MDMA (Ecstasy) depression, 5-HTP 100 mg on Day 3-7 after MDMA use.[xvi]
Successfully supplementing with 5-HTP requires stacking it with a dopamine precursor like L-Tyrosine or L-DOPA along with B-Vitamins (for synthesis), and one of the sulfur-containing amino acids (methionine, cysteine, homocysteine, or taurine).
And you must monitor the effects this stack is having on your body. If you start experiencing side effects of any kind, it’s a good indication that either serotonin or dopamine is out of balance.
DO NOT combine 5-HTP with any kind of antidepressant medication.
Combining SSRI’s, Tricyclics or MAOI’s with 5-HTP will cause Serotonin Syndrome. An extremely dangerous condition involving severe mental changes, hot flashes, rapidly fluctuating blood pressure and heart rate, and possibly coma leading to death.
Serotonin Syndrome can kill you. And I’m not kidding here.
5-HTP Side Effects
5-HTP supplementation can cause heartburn, heart palpitations, headache, stomach pain, nausea, vomiting, diarrhea, drowsiness, sexual problems and muscle issues.
5-HTP can also cause some pretty radical mood changes including agitation, aggressiveness, anxiety, euphoria, poor decision-making, irritability, psychosis, restlessness and insomnia.
5-HTP can make the symptoms of schizophrenia, bipolar disorder and other mental disorders worse.
Serotonin Syndrome
And I can’t emphasize this enough so I’m going to repeat it here in case you missed it…
DO NOT combine 5-HTP with any kind of antidepressant medication. Or with carbidopa.
Combining SSRI’s, Tricyclics or MAOI’s with 5-HTP will cause Serotonin Syndrome. An extremely dangerous condition involving severe mental changes, hot flashes, rapidly fluctuating blood pressure and heart rate, and possibly coma.
And combining 5-HTP with carbidopa also has the potential of causing Serotonin Syndrome.
Serotonin Syndrome can kill you. And I’m not kidding here.
Type of 5-HTP to Buy
5-HTP is made from tryptophan in your body.
5-HTP as a nootropic supplement is made from extracts of the African tree Griffonia simplicifolia. 5-HTP supplements are typically in tablet or capsule form.
You’ll often find 5-HTP in many ready-made vitamin and herbal formulas.
If you are going to stack low-dose 5-HTP with L-Tyrosine I suggest: Natrol 5-HTP Fast Dissolve Tablets (Amazon). Cut the 100 mg tablet into quarters using a pill splitter and dissolve 25 mg 5-HTP under your tongue (sublingually).
Nootropics Expert Recommendation
5-HTP 50 mg up to 3-times per day
I DO NOT recommend using 5-HTP as a nootropic supplement.
Your body does synthesize 5-HTP on its own to make serotonin in your brain. And you can’t get 5-HTP from food. But you can get L-Tryptophan from food which is synthesized into 5-HTP in your body.
5-HTP may help you if you’re dealing with depression. But you must stack if with a dopamine amino acid precursor along with B-Vitamins and a sulfur-containing amino acid. See the “5-HTP Recommended Dosage” in this review above.
IF you are going to try 5-HTP, I suggest starting with a dose of more than 50 mg daily. You may want to take it in the evening because it could help sleep disorders.
Short-term dosing of 5-HTP of no more than 2 weeks seems to provide the most benefit if you’re going to benefit from this nootropic.
Or try using 5-HTP only on an “as needed” basis. For a mood boost, reduce social anxiety, and provide a short-term boost in cognition.
5-HTP supplementation on its own is NOT recommended. Nor is it recommended for long-term use.
Join The Discussion - 343 comments
Wim
August 11, 2018
David,
I read by Sam-e on WebMD: https://www.webmd.com/vitamins/ai/ingredientmono-786/same
“SAMe increases a brain chemical called serotonin. Some medications for depression also increase the brain chemical serotonin. Taking SAMe along with these medications for depression might increase serotonin too much and cause serious side effects including heart problems, shivering, and anxiety. Do not take SAMe if you are taking medications for depression.
(MAOIs) interacts with SAMe “
About the same I read here of 5HTP should not be taken with MAOIs.
What is the effect then if SAM-e and 5HTP are taken both on the same day (or with a small time interval)?
David Tomen
August 12, 2018
Wim, the effects depends on how your body responds to SAM-e and 5-HTP. And the amount of 5-HTP you use. If you are not using any other medications and try SAM-e and 25 – 50 mg of 5-HTP you should be OK and get good results. And the doses are low enough that if you have a negative reaction it shouldn’t be severe.
Michel
March 25, 2018
Hi David, I have another question thatI haven’t found any article talking about it clearly. Here’s the question: I know daylight is crucial for serotonin’s production. Is taking serotonin procursors from food or supplements will produce serotonin even you don’t get outside the entire day or daylight is a must? Thank you
David Tomen
March 25, 2018
Michel, nothing is a “must” but it helps to get outside and some sun whenever you can. Your body craves Vitamin D which is needed to produce all of these neurotransmitters and other hormones. See my blog post on Best Nootropics for Sleep to learn more about how your body ends up in bed every night. https://nootropicsexpert.com/best-nootropics-for-sleep/. The recent review on caffeine also helps to understand this process. https://nootropicsexpert.com/caffeine/
Michel
March 25, 2018
Thank you for the links. Yeah I take 2000 IU of vit D3 everyday and reduce it to 1000 IU in Summer time, because here where I live is cloudy most of the days between October to April.
Michel
March 26, 2018
David, I’ve taking a look at your link. To be honest I have a good idea about the biological clock and the effect of daylight on melatonin which brings around 9pm and stops around 7am… I have been interested about the well being since 2005, nutrition, diets, general and mental health, sport nutrition, ayurveda, Chinese medicine, cooking… The problem in many online articles they don’t precise the information, except some repeted health and medicine instituts. I just want to add one thing here that many people don’t know about it. Caffeine may slow or interact with foods and supplements absobtion. When I want to take a cup of tea or coffee I wait at least 5 hrs after taking my supps or herbs. Or I drink my caffeine then I wait 1hr to take my supps… Caffeine passes the small intestine more quiekly. Thanks again
Michel
March 11, 2018
I just want to add that more than 50 mg a day of 5 htp may cause insomnia. Taking Rhodiola Roses in the evening can cause insomnia as well.
justin rinehart
March 9, 2018
Thanks a lot for that very valuable information, I just got a bottle of NALT 300 MG, for best results should I take it 3 x a day with my 5HTP and nootropics stacks? I don’t want to overdo it and get brain fog.
I already take a High quality fish oil and CDP Choline.
David Tomen
March 9, 2018
Justin, try 300 mg of NALT and see how you feel. You may need to double that dose.
justin rinehart
March 6, 2018
Hi David,
I enjoyed your informative video on 5-HTP, yet this has got to be one of the more complex supplements to understand ( AS far as what to take/ not take with it )
I just wanted to clarify a few things on this product as I just started to take 5-HTP
I am working as well as attending school on top of living in a very high-stress city ( New York )
I have always had bad insomnia and can generally feel stress often
My DR had me on an SSRI long story short several months passed and while you sleep better the side effects are nasty so I weened myself off and insomnia returned The main reason I wanted to try 5HTP is for insomnia as well as mood improvement and an appetite suppressant ( I have read )
I also take a variety of supplements and nootropics ( I don’t drink if that comes in to play )
As you mention it’s important to stack it with certain supplements I wanted to be clear I am doing it right, The product I have is enhanced with vitamin b6/ 50 MG of 5htp to 10 MG of B-6 But I take a separate B-complex vitamin every day as well.
The Neuroscience is very difficult to understand and my concern was you advise against it without stacking it with the right supplements like l- dopamine precursors Therefore I want to be clear on what I must take with it unless I already am.
Is l- tyrosine a MUST or is there something else, as I just started this product I take one 50 MG pill 3 x per day.
Also important to not I don’t have depression or any illness.
For my evening class yesterday I was very tired and took 2 5-HTP with Rhodiola Rosea with 2 l theanine serene which I take every day,
Generally Here are some things I take on a daily basis L-theanine ( serene) It contains L- theanine, gabba, taurin magnesium ( chelate)and some other stuff
cat’s claw
gotu kola
Fish oil
CLA
ALCAR and L-carnitine
ashwagandha
milk thistle ( traded this from dandelion root recently )
b-complex
D3- K2 combination
A quality protein powder 4-5 times a day with BCAA – protein has l-tyrosine in it, is this sufficient?
Ginko Biloba
As well as CDP choline
Koran ginseng ( as a tea every morning )
Phenibut ( It works well yet I just started to take this and I have read a tolerance builds up quickly )
Melatonin ( every night but not very effective)
I tried kava yet I felt nothing on it.
Racetams ( it varies I do not take them every day)
I was considering if I could benefit from bacopa after your recommendation on that product but I tried L-dopa and it did nothing.
I apologize for the long message, I just wanted to be more clear on what to take with 5-HTP and how much and any other supplement for sleep other than what I mentioned
David Tomen
March 6, 2018
Justin, please study this post I wrote on sleep here > https://nootropicsexpert.com/best-nootropics-for-sleep/. I personally use 400 mg magnesium chelated (Doctor’s Best), 500 mg L-Tryptophan, approx. 6 ounces of tart cherry juice (pure from concentrate, NOT a juice blend), and about 25 mg 5-HTP (sublingually). And this stack works wonders for sleep.
Be very cautious with 5-HTP because it a direct precursor to serotonin. Follow dosage instructions closely so you stay out of trouble with this potent nootropic. https://nootropicsexpert.com/5-htp/
Phenibut can be dangerous as well so follow the dosage instructions in the main review > https://nootropicsexpert.com/phenibut/
I’ve personally found melatonin to not be worth the effort. It can really mess with your mood. Very small doses can be OK for some people. I’m talking 0.5 mg types of dosages. Tart cherry juice is safer and provides melatonin (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133468/).
When you are using any of the racetams make sure you follow dosage recommendations including using a choline supplement like Alpha GPC or CDP-Choline.
And you must keep a balance between serotonin and dopamine. You can use L-Tyrosine to boost dopamine. Some find that NALT or Mucuna Pruriens work better. NALT is more bioavailable. And Mucuna is L-DOPA which is a direct precursor to dopamine.
Michel
March 5, 2018
Hi David, Thanks for your answer above. Actually, I take L-tryptophan supplement once a week and another week I take Mucuna pruriens, I leave one week gap between them. Because I have always thought not to work on Serotonin and Dopamine at same time (same day). I have heard that Dopamine needs low sugar and Serotonin needs high sugar.
So, can I take L-tryptophan and Mucuna the same day then?
Thanks a lot
David Tomen
March 5, 2018
Michel, I use L-tryptophan and Mucuna Pruriens on the same day with no problem. But Mucuna before noon and L-Tryptophan before bed.
Michel
March 8, 2018
Thank you indeed
Michel
February 28, 2018
Hi David,
Thank you for all those valuable information in your website. I have two question here please.
– Do you think L-tryptophan supplement requires stacking it with a dopamine precursor like L-Tyrosine or L-DOPA as well? if yes is it 50/50?
– Another question, what do you think about those anxiety supplements that contain 5-HTP among other herbs like Ashwagandha, Lemon balm…without any Dopamine precursors content, in which work very well and after few weeks people have totally recovered from their anxiety symtoms without any side effects?
Thank you
David Tomen
February 28, 2018
Michel, it is really up to the individual what is needed. Certainly, dopamine and serotonin need to be in balance. But my experience is that it takes trial and error over time to find out exactly what is needed. And what works best. And depending on your age and genetic makeup you may find L-Tyrosine works better than L-DOPA. Try L-Tryptophan with L-Tyrosine and see how you feel.
Your second question about 5-HTP is yes, it’ll work for awhile. But not long term because 5-HTP is so potent that long-term use will throw everything out of whack. And you’ll stop experiencing the benefit. That’s been my experience. And what researchers have found during clinical trials.
Other boosters of serotonin and GABA are much safer to use especially long-term than 5-HTP.
Louis
August 22, 2017
Hi david i take 8mg of buprenorphine a day my question is am i ok to take tryptophan or 5htp with the buprenorphine?
Many thanks
David Tomen
August 23, 2017
Louis, buprenorphine affects opiate receptors. And tryptophan and 5-HTP affect serotonin receptors. Two completely different neurotransmitters. Their pathways may affect each other in some manner. But the science is not clear how. So there shouldn’t be an interaction. But I am not qualified to provide advise on whether you should take the two together. Only a licensed health practitioner can offer that advice.