5-HTP

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.

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 2^nd 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.