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 we 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 post. 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.
Table of Contents
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, memory, learning, 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 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.
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 to the rescue
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 headaches. 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 NALT, 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.
The 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.
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, placebo-controlled trial 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 16 years ago.
Dosage Notes
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 our recommended dose, but 5-HTP can be toxic 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.
Serotonin Syndrome can kill you. And we’re not kidding here.
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.
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.
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.
Serotonin Syndrome can kill you. And we’re not kidding here.
Available Forms
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.
Nootropics Expert Recommendation
5-HTP 50 mg up to 3-times per day
We 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 “Dosage Notes” in this post.
IF you are going to try 5-HTP, we suggest starting with a dose of 50 mg daily. You may want to take it in the evening because it could help you sleep.
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, improve 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.
[i] Hinz M., Stein A., Uncini T. “5-HTP efficacy and contraindications.”Neuropsychiatric Disease and Treatment. 2012;8:323-8. (source)
[ii] Turner E.H., Loftis J.M., Blackwell A.D. “Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan.”Pharmacology and Therapeutics. 2006 Mar;109(3):325-38. (source)
[iii] Birdsall T.C. “5-Hydroxytryptophan: a clinically-effective serotonin precursor.” Alternative Medicine Revue. 1998 Aug;3(4):271-80. (source)
[iv] Lemaire P.A., Adosraku R.K. “An HPLC method for the direct assay of the serotonin precursor, 5-hydroxytrophan, in seeds of Griffonia simplicifolia.” Phytochemical Analysis. 2002 Nov-Dec;13(6):333-7. (source)
[v] Emanuele E., Bertona M., Minoretti P., Geroldi D. “An open-label trial of L-5-hydroxytryptophan in subjects with romantic stress.” Neuro Endocrinology Letters. 2010;31(5):663-6. (source)
[vi] Hinz M., Stein A., Uncini T. “APRESS: apical regulatory super system, serotonin, and dopamine interaction.” Neuropsychiatric Disease and Treatment. 2011;7:457-63. (source)
[vii] Hinz M., Stein A., Uncini T. “Relative nutritional deficiencies associated with centrally acting monoamines.” International Journal of General Medicine. 2012;5:413-30 (source)
[viii] van Praag H.M. “n search of the mode of action of antidepressants. 5-HTP/tyrosine mixtures in depressions.”Neuropharmacology. 1983 Mar;22(3 Spec No):433-40. (source)
[ix] Hinz M., Stein A., Uncini T. “5-HTP efficacy and contraindications”Neuropsychiatric Disease and Treatment. 2012; 8: 323–328. (source)
[x] Hinz M., Stein A., Uncini T. “APRESS: apical regulatory super system, serotonin, and dopamine interaction.” Neuropsychiatric Disease and Treatment. 2011;7:457-63. (source)
[xi] Hinz M., Stein A., Uncini T. “Amino acid management of Parkinson’s disease: a case study” International Journal of General Medicine. 2011; 4: 165–174. (source)
[xii] Birdsall T.C. “5-Hydroxytryptophan: a clinically-effective serotonin precursor.” Alternative Medicine Revue. 1998 Aug;3(4):271-80. (source)
[xiii] Shaw K., Turner J., Del Mar C. “Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis.” Australia and New Zealand Journal of Psychiatry. 2002 Aug;36(4):488-91. (source)
[xiv] Caruso I., Sarzi Puttini P., Cazzola M., Azzolini V. “Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome.” Journal of International Medical Research. 1990 May-Jun;18(3):201-9. (source)
[xv] Meyers S. “Use of neurotransmitter precursors for treatment of depression.” Alternative Medicine Revue. 2000 Feb;5(1):64-71. (source)
[xvi]Wang X., Baumann M.H., Dersch C.M., Rothman R.B. “Restoration of 3,4-methylenedioxymethamphetamine-induced 5-HT depletion by the administration of L-5-hydroxytryptophan.” Neuroscience. 2007 Aug 10;148(1):212-20. (source)
I suffer from low serotonin. Do I combine Tryptophan with 5htp or do I use one of them
Boudi, L-Tryptophan is a much safer long-term solution to increasing serotonin. I suggest using only that to increase serotonin.
Hi David,
Is there any information out there on combining Wellbutrin(Buproprion) with the stack you mention in this article? Curious since it is not classified as an SSRI, tricyclic, or MAOI.
Thanks
Mellissa, not sure I understand your question. Do you mean using Wellbutrin with 5-HTP?
Sorry about that. Yes, that’s what I mean. Since it is a different class of drug, do you have any information on it being ok or not ok to use with 5-HTP or in a supplement stack that includes 5-HTP.
Melissa, there is nothing published about them being contraindicated. But that does not necessarily mean it can’t be a problem.
The thing is you are talking about a powerful drug and an equally powerful supplement. I cannot advise you either way except to say be very careful.
Hi David,
I have asked before this question for tryptophan, but was wondering if it applies for 5htp as well.
My question was can I take 5htp with. Am I at risk of getting seretonin syndorm with this combo
* 5htp at night
* Rhodiola
* Ginseng – Eleuthero
* Aswagandha
* Brahmi
* Gotu kola
Thank you.
Nana
Nana, chances are slim but it is possible. 5-HTP much more so than L-Tryptophan because 5-HTP is unforgiving. It immediately begins making serotonin no matter what. L-Tryptophan is gentler and easier to manage the dose.
Thank you David
I am taking 5-htp and Fluoxetine antidepressant meds, and I have no side effects, but the positive effects ended after 6 months. My binge eating and depression are back. As I read here, this combination is dangerous, so I consider stopping with this. Should I start taking L-tyrosine (or Bacopa Monnieri) now, to incrase dopamine level ? and stop with antidepressants and 5-htp? The more I read, the more confused I feel about what to take.
I would be very grateful for the answer.
To add a little background, I have eating disorders and depression 11 years now. Last May I started taking 10mg Fluoxetine (SSRI) and 100mg 5-htp per day. I felt normal for the first time in my life. My relationship with food was healthy and I started loosing some weight. I felt cured. And no side effects at all. But now all the symptomes are coming back: overeating, gaining weight, tiredness, lack of will and motivation. Is dopamine decrease a possible reason for it? What nootropics combination would you suggest to me?
Kind regards from Europe,
Debbie
Debbie, it is well know that 5-HTP stops providing any benefit after 4 – 6 weeks. So you are luckier than most. But the reason it stops working in my opinion (i.e. I can’t prove this) is serotonin over powers dopamine. If you depress dopamine too much bad things happen.
If you have had success with Fluoxetine that means you have problems with serotonin. But higher doses of Fluoxetine (50 – 80 mg per day) also influence dopamine and norepinephrine.
L-Tryptophan is a far safer alternative to 5-HTP and continues to work long-term. I’m NOT suggesting you use it in combo with Fluoxetine. But only bring it up because you were using 5-HTP successfully.
And yes you likely should be increasing dopamine during the day by using L-Tyrosine to keep it in balance with serotonin.
I had higher doses of Fluoxetine in the past, but side effects were too strong (I was so sleepy I couldn’t drive ect.). Then I found 5-htp on my own and when it started working it felt like miracle. But now probably my dopamine decreased too much.
What works better for dopamine: l-tyrosine or Bacopa Monnieri?
I will stop taking SSRI and try with l-tryptophane + l-tyrosine/bacopa monnieri alone. Hope it helps.
Thank you so much for the answer! I deeply appreciate it.
Deborah, I recommend L-Tyrosine for boosting dopamine because it is a direct precursor to the synthesis of dopamine in your brain.
Bacopa Monnieri does not directly affect dopamine.
Hi David,
I am taking the standard 10:1 ratio – 500mg L-Tyrosine with 50mg 5-HTP, for stress, low mood etc
To keep the levels of Dopamine and Seratonin balance throughout the day, is it best to take both at the same time?
….Or, is it best to do what most seem to recommend and take the L-Tyrosine in AM, then 5-HTP in PM?
Im just thinking that as there would be a 10-12 hour gap between me taking the L-Tyrosine in AM and 5HTP in PM, would this not lead to an imbalance during that period as they were not takengat the same time?
Thanks. Carl
Carl, most supplementing with L-Tyrosine during the day take L-Tryptophan before bed. Because dosages are higher.
I don’t suggest using 5-HTP for a number of reasons. Including L-Tryptophan is safer and easier to dose.
The half-life of L-Tyrosine means for all-day benefit you should use it at least twice – AM and noon. Then 500 mg L-Tryptophan before bed.
Hi David, first of all – great article! Ive just stumbled across it and think you may be able to clear up the answer to a couple of questions i have.
I have just started taking the classic 1:10 ration of 50mg 5-HTP with 500mg L-Tyrosine, for general low mood, anxiety, stress etc.
My questions are…
1) Is it better to take both at the same time (in morning) so they balance each other out throughout the day, rather than taking L-Tyrosine in the morning, then 5-HTP in evening?…. which could lead to an imbalance later in the day, as there would be about a 10 hour gap between taking them?
Or, can the balance be maintained by taking them so far apart?
2) Could I take 500mg L-Tyrosine with 50mg 5-HTP in the morning, then an additional 50mg 5-HTP in the evening too? So as to ensure the balance throughout the day, then an extra 50mg to relax me for the evening and bedtime etc? ..Or, as this would turn it into a 1:5 ratio – is this not recommended?
Thanks in advance for your time.
Carl, I’m not a fan of ‘ratios’ for dosing these kinds of supplements. It’s better to use what works in my opinion. If 50 mg 5-HTP + 500 mg L-Tyrosine works for you then stay with it. And use the same small dose of 5-HTP late in the day if that works for you.
I recommend using L-Tyrosine 2 or 3-times during the day when you need dopamine. And L-Tryptophan before bed when you need serotonin/melatonin. That’s the kind of L-Tyrosine dosing that can mess with dopamine/serotonin balance.
Hello David. I use tyrosine and 5-htp. Initially I was using 500 mg tyrosine and 200 mg 5-htp. But I realized that tyrosine was not working. I researched tyrosine again and found it used in much higher doses. The dosage I’m using now is 8 grams per day. I do not feel the effect at lower doses. I guess it’s because of 5-htp. I have no means to use tryptophan and my anxiety problem is really challenging me. I guess I will continue to use 5-htp necessarily. 5-htp really helped my anxiety. However, I am afraid that 5-htp will disappear after a while as you said. I am thinking of boosting 5-htp to 400mg. I also use 250 mg of theanine per day. If you have a better suggestion, could you please help?
Enes, the only other option for directly increasing serotonin is L-Tryptophan. But if you cannot get it then it’ll have to be 5-HTP.
I am convinced the reason 5-HTP stops working for most people after 4 – 6 weeks of daily use is because dopamine/serotonin are out of balance. So long as you keep those two in balance 5-HTP should continue working for you.
David,
Thank you for the in-depth on the subject. Very relevant to me.
Five years ago i took a natural SSRI called Kanna (Sceletium tortuosum) which is a a Dual 5-HT Reuptake and PDE4 Inhibitor for two or three months. Kanna did not do much but provided mild anti-anxiety effects which helped with going through some stressful meetings and events.
At the time i did not understand complex effects this kind of substances have on physiology and delicate neurotransmitter balance. After a few months of Kanna supplementation i have started experiencing GI upset and developed mild form of constipation which has never gone away ever since even though Kanna supplementation was stopped. Never had gut motility issues prior to this experience. Through the years of extensive experimentation with various supplements, lifestyle and diet changes and no effect on the issue i have come to the conclusion that chances are huge that i have slowed down gut motility by SSRI supplementation. I have read is not a rare side effect to experience permanent effects on gut motility with prescription SSRIs.
I have found a study done on rats that discovered slow release 5-HTP improving gut motility in rats with impaired function: https://www.sciencedirect.com/science/article/abs/pii/S0016508519367150
There is also a supplement called MotilPro by Pure Encapsulations which outlines this function in humans:
“5-HTP is absorbed by enterochromaffin cells in the epithelium, in which it is decarboxylated to serotonin using pyridoxal 5’ phosphate as a cofactor. 5-HTP stimulates enteric neurons through activation of 5HT4 receptors. ”
So my interest is in finding an optimal way to supplement 5-HTP to recalibrate receptors in the gut and restore enteric neurons which might have been altered by SSRI supplementation.
As i do not have interest in altering serotonin or dopamine levels in the brain (I do not feel i have depressive behaviours or any dopamine imbalance although you never know i guess) i wonder what is the optimal strategy to use 5-HTP in such case.
I would really love to hear your opinion on this.
Andrew, you’ve thought this through with some good research and I think you’re onto something. The problem is 5-HTP because most people don’t know how to dose it and use far too much. I wonder if you could do a similar thing using L-Tryptophan instead?
I also suggest trying a high quality prebiotic as well. I’ve been using the Performance Lab Prebiotic with amazing results. More on that here: https://bit.ly/2KzeQi2
I’m also looking at motilpro, I was on antidepressants for 15 years and came off 4 years ago but my motility is destroyed and I now have sibo, I think the antidepressant have downregulated my gut serotonin receptors , will motilpro further down regulate my receptors if I try it and then stop?
Daniel, as far as I can tell MotilPro contains Vitamin B6, ginger extract, ALCAR and 5-HTP. I can’t imagine how those ingredients would “downregulate” serotonin receptors.
Is there any nootropic to help repair gut serotonin receptors?
Daniel, not a nootropic but certain intestinal bacteria are involved in serotonin synthesis and transport. For example, Lactobacillus acidophilus and Bifidobacterium longum upregulate serotonin transporter expression according to this study: https://pubmed.ncbi.nlm.nih.gov/29451186/
The science in this area is ongoing and intense. But the bottom-line from what I’ve seen so far is certain prebiotic bacteria and their support is the direction this is going.
Hi David, thank you so much for creating this website and for sharing all of your knowledge. Could you please give me your view on alleviating temporarily lowered serotonin levels?
100mg 5htp
100mg L-theanine
100mg Lemon balm
B vitamins
Given this is for a temporary fix, do I need to worry about adding a dopamine amino?
Thank you so much in advance 🙂
Given this is for temporary
Change 5-HTP for 250 – 500 mg L-Tryptophan which is safer and more effective for use long-term. And you don’t need to worry about dopamine at those dosages. Unless you are low in dopamine too.
Dear David,
brilliant website I must say. I’ve got a couple of questions left after spending my night browsing it, some if which I hope you may find intriguing too. I seem to be quite the opposite of you with a low serotonin and a high dopamine system that I’m trying to tweak into balance.
1. As I suppose many do, I got here researching 5-HTP which I can see you’re not a great advocate of to say the least. You probably already have saved me from enjoying it for 4-6 weeks and staring dumb when it wears off. However, I don’t see similar concerns raised by you about its precursor L-tryptophan. Why the difference? Can dosing of L-tryptophan be that much more accurate and/or does the actual 5-HTP content of those supplements vary that wildly?
I started researching nootropics after a DNA test recommended 5-HTP it for a gene of mine that results in “lower transformation of Tryptophan into 5-HTP” and therefore reduced brain serotonin levels. I’d start with 50mg 5-HTP-s once a day and wouldn’t go over 150mg/day total just having read what I’ve read. Knowing about the gene factor, would you still advise against this and experiment with 500-1000mg of L-Trypto instead?
2. My DNA test also says my dopamine system is very active to start with, due to an especially passive COMT gene massively limiting reuptake. Without the test results, I would simply describe this as being able to feel my frontal lobe exploding under massive stress, and that’s always how I’ve been, so I’d really rather avoid going overboard with dopamine. What’s the lowest dose you’d find it reasonable to start with? Capsules available here are 500mg, but I’m more inclined to get it in powder form and start as low as 50mg, gradually working it up if needed.
3. As for sulfur-containing amino acids, I already take 600mg NAC a day for inflammation as I’m predisposed to heart problems, would that do to keep things in balance?
4. I’m also taking alpha-lypoic acid and turmeric+piperine for inflammation. Would you worry about turmeric acting as a MAOI in the context of 5-HTP or L-Tryptophane? Would taking the Trypto in the morning and turmeric in the evening migitate this risk? There half-lives wouldn’t really overlap that way. (I don’t need help with my sleep, I need help with my day, my mood and my creative focus.)
5. NADH for entering a creative flow sounds really awesome but it’s also ridiculously expensive where I live, the cheapest available is $60 for 60 tabs. Would you argue it’s worth the price? (It’d probably cost more than my entire stack, the rest of which is a vitamin complex and some L-Carnytine on top of the above.)
Really curious about your take on these.
Paul
Paul, if your system has a hard time synthesizing 5-HTP from tryptophan you may be better off with low dose 5-HTP. But do this with eyes wide open. Where people get into trouble is using it to try and treat depression. That has been shown time and again to stop working after 4 – 6 weeks. I think because it suppresses dopamine and they end up dopamine-deficient.
Really the only way to tame dopamine is by raising serotonin. Dopamine and serotonin must be in balance. But that balance is unique to you. If you’ve already got a problem with dopamine I suggest concentrating on serotonin with 5-HTP for now. And leave dopamine alone.
NAC 600 mg 3-times per day will help your brain use dopamine. As well as provide the other benefits it’s known for. Like boosting glutathione.
Monoamine Oxidase Inhibitors (MAOI) raise the catecholamines like dopamine, norepinephrine and epinephrine much more that serotonin. Another reason for you to avoid L-Tyrosine. The problem with Tryptophan or 5-HTP in the morning is it can bring on fatigue. That’s why people use it before bed. If you keep the 5-HTP dose low enough this may not be a problem.
And only thing I can suggest is if you are intrigued by NADH is try it. You may find that it doesn’t provide as much benefit for you as you think. But you’ll never know until you try it.
Dear David,
thank you for reply. I’ll leave an update here in case a search will lead someone with a similar situation here: 2 weeks of 50 mg of 5-HTP is doing wonders, I’ll try 100 mg from tomorrow.
I was getting an interesting side effect though, even mild conflict situations started to cloud my brain to an unfamiliar extent, at the worst point coupled with a massive headache. I’ve only done one dose of NAC before and upped it to two a day, taking the added one with the 5-HTP. Side effects stopped right as I stopped the extra NAC. Looks like NAC alone can kick my dopamine out of balance.
NADH is on the way, will update on that too.
I am experimenting here and there is such conflicting info out there. I was thinking about stacking l-tyrosine, l-theanine, and GABA. I need better focus and concentration and also relief from mild anxiety. Would those three things be ok? and what about dosages? The GABA I bought is 750mg but everything I read recommends no where near that high. like 100-275mg. I’m overwhelmed by all of this.
Heather, you will find dosage recommendations for each of these supplements here on Nootropics Expert (https://nootropicsexpert.com/nootropics-list/).
You’ll also find separate articles on boosting concentration and memory. And at least 2 articles on taming anxiety.
It’s all here for you. And in very easy to understand English. I suggest you start reading. 🙂