5-Hydroxytryptophan (5-HTP) for Sleep

There was a time when sleep was treated as a commodity. Sleep was either good or bad. These were the primary descriptors of both quality sleep and all the different permutations of sleep problems. As we begin to learn more and more about what qualifies as quality sleep and what detracts from it, quality sleep has become a luxury.

Overall, adults need at least seven hours of quality sleep every night for optimum health and well-being.[1] That number can range depending on the individual. However, at least 25-50% of the American population get less than seven hours of sleep every night and the percentage is higher in larger cities.[2]

You probably know about how not getting a good night’s sleep can wreak havoc on your health physically, mentally, and emotionally. That’s one of the reasons why there’s such a large market for prescription and over-the-counter (OTC) sleep-aids. With all the prescription options on the market, many of the natural options can get overlooked. 

But amino acids like 5-HTP are worth taking a deeper look. So let’s dive in.

How neurotransmitters affect sleep

Going back 40 years, scientists didn’t yet understand what was involved in the sleep-wake cycle. Today, we now know that many neurotransmitters in the body are involved in the modulation of sleep. Two main neurotransmitters involved with sleep are serotonin and gamma-aminobutyric acid (GABA).

You may be wondering: how do these neurotransmitters affect my sleep? Good question! 

GABA is the main inhibitory neurotransmitter in the central nervous system. It activates GABA receptors which promote sleep by decreasing the excitability of the central nervous system.[3] GABA is also known for its calming effects on moods such as anxiety, stress, and fear. 

Serotonin has a slightly different role when it comes to sleep. When you think of products that help with sleep, you probably already have heard of the sleep hormone melatonin, which regulates your sleep-wake cycle by making you feel sleepy, signaling to you that it’s time to go to bed. 

Serotonin is is used to make melatonin. Not only is serotonin known for its effects on sleep, but also for appetite, temperature, behavior, and pain sensation. 

While there are foods that you can eat to get GABA in your diet — such as whole grains, soy, lentils, beans, and nuts — it’s more difficult to get serotonin through diet.  

To supplement serotonin, you have to take some of its building blocks, which are amino acids. 

What is 5-HTP? 

There are two main amino acids that can be taken to increase serotonin: L-tryptophan (LT) and 5-Hydroxytriptophan (5-HTP). LT converts into 5-HTP and then 5-HTP makes serotonin. Both LT and 5-HTP are natural, plant-based sleep aids.

Unlike melatonin supplements, which are a form of a synthetic hormone, 5-HTP is extracted from the seeds of an African plant called Griffonia simplicifolia.[5] Clinically, 5-HTP has been used for over thirty years to increase levels of serotonin in the brain. 

LT is an essential amino acid that is found in many foods and supplements, but the key difference between 5-HTP and LT is that LT can be used for the production of other proteins.[5] This simply means that a good portion of the LT that is ingested is not actually used to make serotonin, and in turn, not all is used for sleep. 

As a result, 5-HTP is more effective at making serotonin than LT and therefore is a more potent sleep aid compared to LT. 5-HTP, not only increases serotonin levels, but also affects dopamine and norepinephrine endogenous chemicals that can keep you awake.[5] This allows 5-HTP to regulate your sleep slightly differently compared to LT.  

How does 5-HTP work on sleep? 

In treating insomnia, 5-HTP has been shown to be beneficial in improving sleep quality by increasing rapid eye movement (REM) sleep.[7] REM sleep is a phase of sleep in which most dreams take place and it is thought to play an important role in learning, memory, and mood. 

In one study monitoring the effects of 5-HTP on REM sleep, researchers were able to demonstrate a significant increase in the amount of REM sleep observed when subjects were taking 5-HTP. [7] They found REM sleep increased 5 to 53% from placebo baseline across all subjects, representing an average increase of 16 minutes per night.[7]

Although 600mg of 5-HTP was used in the study, it may be beneficial to take smaller doses because larger doses did have reports of patients experiencing vivid dreams or nightmares.[7]

What else is 5-HTP used for?

5-HTP supplements have been studied for alleviating the symptoms of migraines, since many drugs that affect serotonin are used to combat migraines. There is some evidence that 5-HTP can help reduce symptoms associated with anxiety disorder and panic disorder, both of which are associated with sleep disturbances. 

5-HTP has been used in clinical trials for the treatment of primary fibromyalgia syndrome. Since fibromyalgia is associated with low serotonin levels, individuals with this condition commonly report improvements in deep sleep and pain after the use of 5-HTP. 


As a natural sleep aid, 5-HTP has very few interactions. As 5-HTP has an effect on the body’s production of serotonin, it’s worth considering this before taking OTCs or prescription drugs that may also increase serotonin levels and/or medications that have a depressive/tranquilizing effects. 

Combining 5-HTP supplements and medications such as antidepressants (including SSRIs), dextromethorphan, meperidine, monoamine oxidase inhibitors (MAOIs), pentazocine, phenothiazines, and tramadol may increase the risk of serotonergic side effects such as serotonin syndrome and cerebral vasoconstrictive disorders such as Call-fleming syndrome. 

Medications that depress the central nervous system also interact with 5-HTP. Taking 5-HTP with medications like benzodiazepines and opioids are associated with additive sedation effects. This combination may be very dangerous to the elderly due to risk of falls. 

Fortunately, there are no known food interactions. You can take 5-HTP with or without food because its absorption will not change whether or not there is food in the stomach.[5]

How 5-HTP moves and changes in your body6

After taking 5-HTP, it moves from your gut into the rest of your body.  The highest concentration of 5-HTP in the blood occurs between one to three hours after taking it. It then moves from the blood and crosses the blood-brain barrier. This is actually why LT is converted to 5-HTP, because LT can’t cross the blood-brain barrier.

Once it has crossed the blood-brain barrier, this is where it begins to make serotonin, which helps with sleep. Not all of the 5-HTP that you take has an active effect. About 70% of the 5-HTP that you take will be used. So what happens to the 30% that isn’t active? For the most part, it is eliminated from the body unchanged in the urine. 

It can also be metabolized (chemically changed to an inactive form) in the liver or kidneys. It takes between two to six hours for the 5-HTP concentrations in the blood to go from 100% to 50% and then around eight to 24 hours for the concentrations to be considered negligible with regard to its therapeutic effects. 

Side Effects[6]

In general, 5-HTP can be taken with little to no side effects; however, when taking 5-HTP in very large doses, you could experience some adverse effects. These possible side effects are uncommon, but they are important to watch out for if you do take large doses of this amino acid.

  • Cardiovascular: Palpitations, Bradycardia, Diastolic Hypotension
  • Dermatologic: Urticaria, Allergic skin reactions, Flushing
  • Gastrointestinal: Nausea, Vomiting, Stomach pain, Heartburn, Diarrhea, Flatulence, Weight-loss, Taste Alteration
  • Hematologic: Eosinophilia Myalgia syndrome,
  • Musculoskeletal: Rhabdomyolysis
  • Neurologic: Drowsiness, Dizziness, Insomnia, Fatigue, and Headache
  • Psychiatric: Euphoria, Hypomania, Anxiety, Aggressiveness 

Dosing and Safety[6]


There is some clinical evidence showing it is safe use when used orally and appropriately in doses up to 400mg daily for up to one year. Higher doses have been used safely for between three weeks and 10 months. 


There is some clinical evidence showing its safe use when used orally and appropriately in doses up to 5mg/kg daily have been used safely for up to three years in infants and children up to 12 years old. 

Pregnancy and Lactation

There is insufficient reliable information available; avoid using. 

How we use 5-HTP

Remrise formulations incorporate 5-HTP in the weekly rotation because of its multitude of benefits for sleep. Specifically, its action on REM sleep cycles and its ability to nudge the release of that sleep optimizing hormone, serotonin. 

Each sleep phase is crucial, but we all know how important regular REM is for mood, memory and learning. Accessing serotonin also imbues the mind and body with relaxation and decreases anxiety, which can affect our ability to fall asleep. 

We blend 5-HTP with GABA to improve different elements of your sleep patterns. Both enhance relaxation to improve sleep in different ways. GABA makes it easier to fall asleep while 5-HTP improves overall quality of sleep. Early research on this combination shows that this synergistic effect is enhanced when 5-HTP is combined with GABA. 


5-HTP is one of many safe, complementary supplements for sleep. The reason why the market is so saturated with many different sleep-aids is because each person is different. 

What may work for you won’t necessarily work for others. It is important to do your research when making the right decision for yourself. 


  1. Watson NF, Badr MS, Belenky G, et al.; Consensus Conference Panel. Joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society on the recommended amount of sleep for a healthy adult: methodology and discussion. Sleep. 2015;38:1161–1183.
  2. CDC. Data and Statistics: Sleep and Sleep Disorders. (2017, May 2). Retrieved from https://www.cdc.gov/sleep/data_statistics.html
  3. Gottesmann C. GABA mechanisms and sleep. Neuroscience. 2002;111(2):231-9. Review. PubMed PMID: 11983310.
  4. Portas CM, Bjorvatn B, Ursin R. Serotonin and the sleep/wake cycle: special emphasis on microdialysis studies. Prog Neurobiol. 2000 Jan;60(1):13-35. Review. PubMed PMID: 10622375.
  5. Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. Review. PubMed PMID: 9727088.
  6. 5-HTP. (19, April 16). Retrieved from https://naturalmedicines-therapeuticresearch-com.proxy.hsl.ucdenver.edu/databases/food,-herbs-supplements/professional.aspx?productid=794#scientificName.
  7. Wyatt RJ, Zarcone V, Engelman K, et al. Effects of 5-hydroxytryptophan on the sleep of normal human subjects. Electroencephalogr Clin Neurophysiol 1971;30:505-509.
  8. Hong KB, Park Y, Suh HJ. Sleep-promoting effects of a GABA/5-HTP mixture: Behavioral changes and neuromodulation in an invertebrate model. Life Sci. 2016 Apr 1;150:42-9. doi: 10.1016/j.lfs.2016.02.086. Epub 2016 Feb 26. PubMed PMID: 26921634


  • Amino Acid: building block for enzymes and protein
  • Call-fleming syndrome: it is a disease characterized by weeks-long course of thunderclap headaches, sometimes focal neurologic signs and occasional seizures. 
  • Eosinophilia Myalgia syndrome: it is a rare disorder that causes inflammation in different parts of the body including muscle, skin and lungs. It causes high levels of white blood cells known as eosinophils. 
  • Flushing: in relation to a person’s skin/face becoming red and hot 
  • Hypomania: mild form of mania, marked by elation and hyperactivity
  • Bioavailability: the proportion of a drug that is able to have an active effect. 
  • Distribution: In pharmacology, it describes the reversible transfer of a drug from one location to another within the body. 
  • Elimination: how t the drug is removed from the body. 
  • Neurotransmitter: a chemical substance that is released at the end of a nerve fiber from a nerve impulse that causes the transfer of an impulse to another nerve fiber or another structure. 
  • Rhabdomyolysis: destruction muscle cells
  • Serotonin syndrome: group of symptoms that may occur with the use of certain serotonergic medications. Symptoms include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils and diarrhea. 
  • Urticaria: rash of round, red welts on the skin that itch intensely.