5-HTP – An Overview
5-HTP (5-Hydroxytryptophan) is a naturally occurring amino acid that may have a nootropic effect when taken as a supplement. Many people use it for:
- Treating depression
- Reducing anxiety
- Improving sleep and fighting insomnia
- Addiction recovery
What Is 5-HTP?
5-HTP is a naturally occurring extract found in the seeds of the African plant Griffonia simplicifolia and is the immediate precursor to serotonin.
Serotonin is one of the major neurotransmitters associated with mood, motivation, sleep and other major functions.
Supplementing with 5-HTP has been shown to raise serotonin levels in many clinical settings.1Turner EH, Loftis JM, Blackwell AD. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan Pharmacol Ther. 2006 2UDENFRIEND S, WEISSBACH H, BOGDANSKI DF. Increase in tissue serotonin following administration of its precursor 5-hydroxytryptophan J Biol Chem. 1957 3Trachte GJ, Uncini T, Hinz M. Both stimulatory and inhibitory effects of dietary 5-hydroxytryptophan and tyrosine are found on urinary excretion of serotonin and dopamine in a large human population Neuropsychiatr Dis Treat. 2009
You usually synthesize serotonin from tryptophan, which is an amino acid typically found in poultry, dairy, and some vegetables.
However, if you aren’t getting enough tryptophan, or your body is not converting it efficiently, you may end up with a serotonin deficiency that could lead to a number of issues.
5-HTP is one of the most popular over the counter supplements, although actual evidence that it is effective is very mixed.
As you will see, simply trying to manipulate one neurotransmitter system (serotonin) may not be the most effective way to treat the disorders it is often used for.
What Does 5-HTP Do?
5 HTP For Depression
This nootropic is one of the most popular “natural” solutions for depression on the market.
Although some people claim success with this product, the actual science behind it is quite spotty.
It actually may be more harmful than helpful for many people.4Marty Hinz, Alvin Stein, and Thomas Uncini. 5-HTP efficacy and contraindications Neuropsychiatr Dis Treat. 2012 5Shaw K, Turner J, Del Mar C. Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis Aust N Z J Psychiatry. 2002
Serotonin and Mood
For decades, researchers have studied the relationship between the serotonergic system and depression.
Although some have stated “there is now substantial evidence that unmedicated depressed patients have abnormalities in brain 5-HT function,” they contend that the “relation of these abnormalities to the clinical syndrome is unclear.”
In other words, we know that serotonin is a critical part of understanding depression, but we don’t precisely know its role.
There are some studies, mostly on primates, that suggest serotonin manipulation (like with 5-HTP) could positively affect mood and emotional processing.6Merens W, Willem Van der Does AJ, Spinhoven P. The effects of serotonin manipulations on emotional information processing and mood J Affect Disord. 2007 7Shaw K, Turner J, Del Mar C. Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis Aust N Z J Psychiatry. 2002 8Chamberlain B, Ervin FR, Pihl RO, Young SN. The effect of raising or lowering tryptophan levels on aggression in vervet monkeys Pharmacol Biochem Behav. 1987
However, some say that the pharmaceutical industry has mischaracterized and oversimplified this relationship in order to market drugs like SSRI’s and remedies like 5-HTP, which work primarily on serotonin.9Cowen PJ. Serotonin and depression: pathophysiological mechanism or marketing myth?Trends Pharmacol Sci. 2008
As one meta-analysis of current research puts it “Serotonin function is related to several aspects of emotional information processing, but it is unknown whether these changes predict or have any relationship with clinical outcome – the causal link between serotonin and impaired attention remains elusive, as do the underlying biological mechanisms mediating these effects.”10Merens W, Willem Van der Does AJ, Spinhoven P. The effects of serotonin manipulations on emotional information processing and mood J Affect Disord. 2007
It is also important to note that some people feel more depressed after taking 5-HTP, indicating that raising serotonin levels may not be a useful treatment in and of itself.
5-HTP and Dopamine
It is also important to understand that increasing serotonin can also deplete dopamine at the same time.
Dopamine is also implicated in mood disorders like depression.
This can mean that if you try to raise serotonin, you could end up lowering dopamine, inadvertently worsening your depression.
Brain chemistry involving depression is complex and still not fully understood. It is possible that 5-HTP may have some role in treating this condition in a supporting role to other medications and therapies.
If you do decide to take 5-HTP for this reason, it may be a good idea to take a dopamine supplement (such as NALT/L-tyrosine) to balance out this side-effect.11Hinz M, Stein A, Uncini T. APRESS: apical regulatory super system, serotonin, and dopamine interaction Neuropsychiatr Dis Treat. 2011
5-HTP and OCD
There is some preliminary evidence that serotonin transport is connected to OCD severity, which could be helped by 5-HTP.
However, evidence is currently scarce, and more study is needed.12Zitterl W, et al. Changes in thalamus-hypothalamus serotonin transporter availability during clomipramine administration in patients with obsessive-compulsive disorder Neuropsychopharmacology. 2008
Is 5 HTP Good For Anxiety?
5-HTP could be an effective solution for anxiety, as anxiety works along the same serotonergic pathways as depression.
However, the same caveats apply for treating anxiety with 5-HTP as they do with depression.
There is not a lot of strong evidence from human trials that just modulating serotonin can decrease anxiety.13Gorman JM. Comorbid depression and anxiety spectrum disorders, Depress Anxiety. 1996
5-HTP and Addiction
There is evidence that 5-HTP can help in recovering from addictions. The serotonin pathway is implicated in many types of substance abuse.
5-HTP has shown promise as a recovery aid, although most studies have demonstrated its role as a complement to other therapies.
There is not much evidence showing 5-HTP’s effectiveness as a stand-alone therapy for addiction.
For example, 5-HTP has been shown to modulate neurotransmitter function while limiting the negative effects of stimulants. This indicates it could be used for cocaine and amphetamine addiction recovery.14Michael H. Baumann, et al. Serotonin (5-HT) Precursor Loading with 5-Hydroxy-L-tryptophan (5-HTP) Reduces Locomotor Activation Produced by (+)-Amphetamine in the Rat Drug Alcohol Depend. 2011
One rat study found that it could be useful for “reducing alcohol intake and suppressing alcohol withdrawal seizures.”15Halladay AK, et al. Alterations in alcohol consumption, withdrawal seizures, and monoamine transmission in rats treated with phentermine and 5-hydroxy-L-tryptophan, Synapse. 2006
One study demonstrated that 5-HTP as part of combination therapy could significantly reduce the withdrawal symptoms and mood symptoms among a group of Chinese heroin addicts.
However, this was only a 6-day trial.16Chen D, et al. Neurotransmitter-precursor-supplement intervention for detoxified heroin addicts, J Huazhong Univ Sci Technolog Med Sci. 2012
5-HTP and Fibromyalgia
One study found that clinical parameters of fibromyalgia were significantly improved by treatment with 5-HTP. Only mild and transient side-effects were reported.17Caruso I, et al. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome, J Int Med Res. 1990
Another study saw the combination of MAOIs (monoamine oxidase inhibitors) with 5-HTP significantly improved fibromyalgia syndrome, compared to other treatments.18Nicolodi M, Sicuteri F. Fibromyalgia and migraine, two faces of the same mechanism. Serotonin as the common clue for pathogenesis and therapy, Adv Exp Med Biol. 1996
These are promising results.
However, we do need more evidence from large, high-quality studies that 5-HTP alone helps fibromyalgia.
Does 5 HTP Help For Headaches?
Evidence regarding this nootropic and headaches are mixed.
There is some evidence that 5-HTP can improve migraine symptoms.
Most of the studies found that this supplement can improve the frequency, intensity and duration of the headaches.19De Giorgis G, et al. Headache in association with sleep disorders in children: a psychodiagnostic evaluation and controlled clinical study–L-5-HTP versus placebo, Drugs Exp Clin Res. 1987 20Titus F, Dávalos A, Alom J, Codina A. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial, Eur Neurol. 1986 21Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. For the Portuguese Head Society, Headache. 2000
On the other hand, brain scans reveal elevated levels of serotonin (5-HT) in some people who experience migraines. Since 5-HTP increases 5-HT this might not be a great solution for many migraine sufferers.22Marie Deen, et al. High brain serotonin levels in migraine between attacks: A 5-HT4 receptor binding PET study Neuroimage Clin. 2018 23Deen M, et al. Migraine is associated with high brain 5-HT levels as indexed by 5-HT4 receptor binding, Cephalalgia. 2019
5-HTP and ADHD
The relationship between brain serotonin and the mind’s ability to focus has been subject to a number of studies measuring the effects of 5-HTP and SSRI’s.
The results with 5-HTP specifically have been mixed and seem to implicate a number of factors with the subject.
In one study 5-HTP increased attention in subjects with low baseline attention yet decreased it in those with high baseline attention.24Hannah Weinberg-Wolf, Nicholas A. Fagan, George M. Anderson, Marios Tringides, Olga Dal Monte & Steve W. C. Chang. The effects of 5-hydroxytryptophan on attention and central serotonin neurochemistry in the rhesus macaque, Neuropsychopharmacology volume. 2018
Overall there seems to be good evidence that 5-HTP can help alleviate symptoms of ADHD
5-HTP For Memory
There is evidence that a number of serotonin receptors play a role in both short term and long term memory consolidation.25Alfredo Meneses. Serotonin, neural markers, and memory, Front Pharmacol. 2015;
This may be due to the phenomenon of sensitization, which is an increase in response to a stimulus that depends on the secretion serotonin.26Eduardo Camina, Francisco Güell. The Neuroanatomical, Neurophysiological and Psychological Basis of Memory: Current Models and Their Origins, Front Pharmacol. 2017
5-HTP may be helpful with this serotonin production.
5-HTP For Sleep
Serotonin is critical for regulating sleep-wake cycles. One of the byproducts of serotonin production is melatonin, a hormone closely associated with sleep patterns.27Jonathan D. Morrow, et al. Effects of Serotonergic Activation by 5-Hydroxytryptophan on Sleep and Body Temperature of C57BL/6J and Interleukin-6-Deficient Mice are Dose and Time Related, Sleep. 2008
This means that 5-HTP could theoretically improve some aspects of sleep, although no human studies confirm this.
Despite this, 5 HTP and melatonin has become a popular stack for many people looking to improve their sleep.
How 5-HTP Works In The Brain
Your body creates serotonin by metabolizing dietary tryptophan into 5-HTP, which then metabolizes into serotonin.
Taking 5-HTP extract directly cuts out a step, raising serotonin levels faster.
5-HTP becomes serotonin through the action of the L-aromatic amino acid decarboxylase (AAAD) molecule.
This is the same compound that metabolizes dopamine.
Monopolizing L-aromatic amino acid decarboxylase to create serotonin could mean lower dopamine levels which could lead to unintended side-effects.28Hinz M, et al. APRESS: apical regulatory super system, serotonin, and dopamine interaction, Neuropsychiatr Dis Treat. 2011
Serotonin is a monoamine neurotransmitter that plays a complex and multifaceted role in many cognitive processes.
It can affect mood, motivation, sleep, sexual function, cognition, reward, learning, memory, and more.
How Much 5-HTP Should I Take?
The dosage ultimately depends on what you are using 5-HTP for.
For mood and cognitive effects, studies have looked at 150-3000 mg daily in up to three divided doses, usually with food. It may take up to 2-6 weeks to start seeing effects.
5-HTP Potential Side Effects
The most important guideline to remember is that YOU SHOULD NOT TAKE 5-HTP WITH ANTIDEPRESSANT MEDICATION OR MAOIs.
This could lead to a potentially deadly condition called serotonin syndrome.
Medications To Avoid While Taking 5-HTP
These drugs include: fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Tofranil), phenelzine (Nardil), tranylcypromine (Parnate). Side effects can include heart problems, anxiety, breathing problems, depression, and more.
Overall it’s best to avoid combining 5-HTP with any other medications that affect serotonin in the brain. These include Dextromethorphan, Meperidine (Demerol), Pentazocine (Talwin), Tramadol (Ultram)
Avoid Sedatives While Taking 5-HTP
Because Serotonin is eventually converted into melatonin, sedative medications can cause excessive sleepiness and drowsiness. These include clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), zolpidem (Ambien)
Supplement and Herbal Interactions
Avoid sedative herbs including calamus, California poppy, catnip, hops, Jamaican dogwood, kava, St. John’s wort, skullcap, valerian, yerba mansa,
Avoid Serotonergic herbs including Hawaiian baby woodrose, L-tryptophan, S-adenosylmethionine (SAMe), and St. John’s wort
Potential Side Effects of 5-HTP
- Stomach pain
- Sexual problems
- Muscle pain.
5-HTP is POSSIBLY UNSAFE when taken by mouth in large doses. Doses from 6-10 grams daily have been linked to severe stomach problems and muscle spasms.
Some users also claim that 5-HTP can make their mood disorders worse instead of better. Because we have such an incomplete understanding of serotonin’s role in mental health, you should approach this supplement cautiously.
Do you have questions about, supplementing with 5-HTP? Do you have experience supplementing with 5-HTP? Please share your thoughts in the comments below.
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