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
jayp
February 1, 2019
You mention sulfur amino acid to stack with 5htp, when should you take it if you are stacking with Tyrosine, because i take all 4 in the morning with no breakfast. Then eat a late lunch. I do this as part of my lowering insulin. I know this works as i have tested labs and insulin lowered to 6. There is pleny of literature on lowering blood glucose through interval fasting.
Jim Lucoff
January 29, 2019
I’m trying to inhibit melatonin inhibition caused by light. Situation is that I go to meeting every Monday evening flooded with bright lights. Every Monday night I can’t sleep. I’ve tried blue light blocking glasses with very limited results. Will 5-HTP sustained release form taken in low dosage help me sleep after being exposed to bright light?
David Tomen
January 29, 2019
Jim, you are better off using supplements shown to act as a natural blue light filter. Please check out my review of this Vision supplement here: https://nootropicsexpert.com/performance-lab-vision-review/
Mark
January 17, 2019
Hi David,
Thanks for this informative article. It has opened my eyes about the pros/cons of 5HTP. Taking into account the risks that you have highlighted and your dosage recommendations for 5HTP, I would like to trial the stack that you have recommended using 5HTP with L-Tyrosine and Taurine (plus B Vitamins).
Using this stack, what would be your dosage recommendations for L-Tyrosine and Taurine, if I am taking 150mg – 300mg of 5HTP per day? I will be tracking potential side affects daily.
Thanks in advance,
Mark
David Tomen
January 18, 2019
Mark, follow the dosage recommendations in the reviews for L-Tyrosine and Taurine. Your 5-HTP dose will likely work better at the lower end. Try 100 – 150 mg and see how that feels. Possibly split in two or three smaller doses during the day.
Zeshan
December 9, 2018
Hi david,
Is it okay to take aniracetam and 5 htp together? I’m taking L tyrosine and and 5 htp at the moment. Can you recomment me a safe ratio for l tyrosine and 5 htp? and also is it okay to include aniracetam in my stack? I see your videos on youtube and know that SSRIS and 5htp can be fatal. SSRIS are considered anti depressants, and aniracetam is considered a supplement for SSRIS and in some places it’s called an anti-depressant. So is it okay for to add aniracetam in my stack.
David Tomen
December 10, 2018
Zeshan, you can use Aniracetam in your stack but you need to add either Alpha GPC or CDP-Choline too. Please check the dosage notes.
There is no ‘safe ratio’ for tyrosine and 5-HTP. You know that one raises dopamine and the other serotonin. These two neurotransmitters must be in balance. But it’s different for everybody.
For example, I personally use NALT 800 mg 3-times per day. But only use about 100 mg 5-HTP split into 4 doses of 25 mg each throughout the day depending on how I’m feeling. This dosage may be very different to you.
Cameron
November 7, 2018
Hi David
I stumbled on to your Youtube video about 5HTP after hearing about 5HTP as a post-party-blues cure. From my very basic knowledge of the human brain – I extrapolated that it could have long term effects as a prescription-less cure for depression and anxiety.
There is a history of depression in my family – My dad is currently on anti-depressants and I am experiencing similar symptoms to his but I don’t currently have access to a mental health professional.
My question is: Would you recommend any other supplement or medication that doesn’t require a prescription from a doctor to help manage my social anxiety and depression? My current plan is to take 100mg of 5HTP coupled with a Vit B rich multivitamin and 350mg of NALT with breakfast every morning. I also have a CBD vape which helps to ease the symptoms but it’s not strong enough on its own.
I thank you for your help in advance
Kind Regards
Cameron
David Tomen
November 7, 2018
Cameron, it may work. But depression and anxiety is more complex than the pharmaceutical companies would have you believe. Because they haven’t figured it out yet either.
One of the reasons is because the cause can vary widely from person to person. See my post on depression here > https://nootropicsexpert.com/best-nootropics-for-depression/
The dosages you are suggesting are low enough that you should stay out of trouble. You need to be particularly careful with 5-HTP because it is a direct precursor to serotonin. And if you don’t have a serotonin issue …
Asimo1
September 19, 2018
Hello David,
I really appreciate your knowledge about notropic, following you for long time (from Bosnia).
Have a questions for you…
In a past for few times I had problem with tyroid gland TSH, hyperthyroidism. But everything was OK for last 2-3 years.
Before 15-20 days I start to use some notropic components, rhodiola rosea, vinpocetine, Alpha-GPC, Noopept, Ginko, Huperzine-A and before few days I add 5-HTP to my stack.
I start to have all symptom hyperthyrodism again (nervousness, headache, heart beat, neck pain).
So my question is, do you think this is because 5-HPT, high serotonin cause hyperthyroidism or something else from my stack ?
What to do now, stop with everything or kick out 5-HPT
Also, what do you suggest to take for slow TSH without medical.
Thanks a lot.
Thanks.
David Tomen
September 19, 2018
Sounds like 5-HTP could be the culprit here. 5-HTP is an extremely potent nootropic because it is a direct precursor to the synthesis of serotonin. It’s very easy to use too much 5-HTP which will increase serotonin and in turn suppress dopamine.
Instead of 5-HTP, you may want to try something gentler like L-Tryptophan. But take it about 90 minutes before you go to sleep.
And consider gently boosting dopamine as well with some L-Tyrosine but earlier in the day.
Asimo1
September 19, 2018
Thanks.
I will kick out 5-HtP.
So what about to take Iodine in my case ?
Do I need to kick out anything else from stack? Noopept ?
Also .. I already order SAM-e, lithium and sulbutiamine..now afraid to take anything without your advice ..
Thanks David
David Tomen
September 19, 2018
The rest of your stack looks safe as long as you follow the dosage recommendations included in each review for these nootropics. I think most need to supplement with iodine because most of us are deficient. But dosing iodine is more difficult because we have individual needs. I find that personally, the 150 mcg of iodine included in my multivitamin supplement is adequate.
Natalia
August 27, 2018
Hello David. Thank you for a wonderful article. I’m Natalia and have been experiencing depletion of my dopamine and serotonin levels because of the 2 medications I’m taking at the moment. I’m on a quitting cut down program right now and would like to substitute with substances to balance my dopamine and serotonin back to normal. I’ve done a lot of research and would like to try L-Tyrosine and 5-HTP together in the morning 500mg:50mg, and what you have suggested for sleep in the evening. Would the morning combination be ok for me for a start? Will I have any side effects such as lethargy from 5-HTP or will they balance each other out? Thank you very much in advance.
David Tomen
August 27, 2018
Natalia, your intended stack of L-Tyrosine and 5-HTP is a good starting point. The doses are low enough that they should not cause side effects. While keeping dopamine and serotonin in balance which is key.
Kate Brown
August 12, 2018
Six years ago I experienced a severe depression following prolonged stress. This precipitated debilitating insomnia which, despite every non-pharmaceutical intervention, I have been unable to resolve. Prior to this time I enjoyed good sleep and am currently otherwise physically healthy and am not under any major stress.
.
Recent cortisol testing revealed that my cortisol is slightly elevated at night and my melatonin level is low.
For the past month, I have been trialling doses of 5htp, with some improvement – 50 mg morning and afternoon and 200mg at night, along with 1g GABA, 3 mg time release melatonin and 2 Seriphos.
B vitamins are too stimulating for me at any time of the day but I have a good diet.
However, while the above supplements give me a 3-5 hour initial block of sleep, I am still waking in the very early hours (b/n 1- 3 a.m.) and unable to get back to sleep no matter what I do or take then. I am reluctant to increase bedtime doses without supervision.
I have also briefly tried tryptophan (2 x 500g at bedtime) along with the other listed supplements, with similar results – good first block of sleep but early waking and side effects of dry mouth and constipation which has inclined me to favour 5htp.
However, because you prefer tryptophan for sleep and experimenting without guidance risks a worse outcome. I would like your opinion on dosage and timing.
Do you think a larger than 1g dose of tryptophan at bedtime or an additional daytime dose would help me sleep longer than 4-5 hours at night? Any other thoughts would be most welcome. Thank You
David Tomen
August 13, 2018
Kate, I understand what you are going through because I have as well. Last night I woke up once and fell back in a deep sleep until my normal 5 AM. And this is what I used:
Performance Lab Sleep: https://nootropicsexpert.com/performance-lab-sleep-review/
Magnesium chelate – 400 mg
L-Tryptophan – 500 mg
25 mg sublingual 5-HTP
4 oz of tart cherry juice
1 tablespoon of raw honey
My Performance Lab Sleep review has a link to another post I did on sleep. Which has links to the individual nootropics and how they work.
All was taken about 90 minutes before I went to bed. The raw honey was right before bed and is used to prevent a sugar crash in the middle of the night.
Tart cherry is a natural source of melatonin. I’ve tried synthetic melatonin and it didn’t worked out so well. My mood the next day was awful.
Magnesium will help get rid of your constipation and is a wonderful sleep aid.
The two nights prior I forgot to take Performance Lab Sleep. Both nights I woke in the middle of the night and couldn’t get back to sleep. I don’t know what it is about that combo. You may want to try it along with the rest of the stack here.