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5-Hydroxytryptophan (5-HTP) for Anxiety

The brain needs L-tryptophan and 5-hydroxytryptophan (5-HTP) to manufacture serotonin.

L-tryptophan and 5-HTP are widely used alternative treatments of generalized anxiety. Both amino acids are essential for the manufacturing of serotonin in the brain. Serotonin is a neurotransmitter that plays a central role in the regulation of mood and anxiety. Greater research evidence supporting the use of 5-HTP for anxiety, together with smaller effective doses and increased CNS availability, generally make 5-HTP the preferred choice over L-tryptophan.

5-HTP reduces the severity of generalized anxiety.

More research has been done on 5-HTP than l-tryptophan. In a double-blind study, 58 percent of generally anxious patients (79 total subjects) randomized to L-tryptophan 3 grams per day reported significantly greater reduction in baseline anxiety compared to individuals who received a placebo. Both animal studies and human clinical trials show that 5-HTP has anti-anxiety effects. There is some evidence that 5-HTP may also inhibit panic attacks induced by carbon dioxide.

The uses of 5-HTP in integrative psychiatry.

In the rapidly growing field of integrative psychiatry, prescription medications and natural supplements are often used in combination to improve treatment response and reduce side effects resulting when medications are taken alone. 5-HTP is an example of a natural supplement that may be safely combined with a prescription anti-anxiety medication with little risk of adverse effects. In one study, patients randomized to 5-HTP in combination with carbidopa (a drug that inhibits the enzyme that breaks down 5-HTP in the peripheral blood supply, thus increasing the amount of 5-HTP that enters the brain) reported reductions in anxiety comparable to patients treated with an anti-anxiety medication. In contrast, patients who received a placebo did not improve.

Starting 5-HTP at a low dose reduces the risk of side effects.

Some individuals who take 5-HTP report daytime fatigue or sleepiness. There have been infrequent reports of mild serotonin syndrome, a condition caused by excessive brain serotonin associated with insomnia, agitation, and nervousness. The risk of serotonin syndrome and other adverse effects is minimized when 5-HTP is started at low doses, such as 25 milligrams per day, and gradually increased over several weeks to a daily regimen that is well tolerated and produces beneficial anti-anxiety effects.

In over 20 years as an integrative psychiatrist, I have found that 5-HTP—50 milligrams to 100 milligrams taken three times a day—is a safe and effective approach for chronic generalized anxiety that is well tolerated without excessive daytime sedation. 5-HTP may be taken alone or in combination with anti-anxiety medications.

Taking 5-HTP at bedtime improves sleep and reduces daytime anxiety.

Gradually increasing a bedtime dose of 5-HTP from 50 milligrams to 200 to 300 milligrams over a period of two to three weeks often improves the quality of sleep in chronically anxious patients who complain of insomnia while also reducing the severity of daytime anxiety.

Find a quality brand of 5-HTP.

When considering taking 5-HTP or any natural supplement, it is important to find a brand known to be both effective and safe. I do not recommend particular brands to my patients. However, my website includes links to web resources that will help you identify quality brands.


What’s 5-HTP Used For?

An amino acid, 5-HTP or 5-Hydroxytryptophan, helps create serotonin, a chemical in the brain. Low serotonin levels in humans can cause several health problems such as obesity, depression, headaches and muscular aches and pains. Many of these side effects can be helped and possibly eliminated if serotonin levels in the brain are elevated, which is where 5-HTP comes in.

How Long Does It Take to Work?

The dosage and length of time 5-HTP takes to work depends on why a person is taking the amino acid. If someone suffers from headaches, depression or weight problems, then it’s recommended to take 50 mg of 5-HTP three times a day. In one to two weeks, the person should feel a difference and see some results. If nothing seems to change, the dose can be increased to 100 mg. It’s recommended to take 5-HTP as capsules or tablets to avoid nausea. If a person is taking 5-HTP to combat insomnia, he should take 100 to 300 mg approximately 30 to 45 minutes before bedtime, and it should take about three days to begin to work. If a person plans to take 5-HTP continuously, he should be aware that there are some problems that have been found when taking more than 300 mg of this supplement a day for long periods of time. Be sure to check in with your doctor if this is the case.

How Does 5-HTP Effect the Body?

The human body naturally creates 5-HTP from tryptophan, an amino acid. In the body, 5-HTP is used to produce serotonin. Supplements, such as 5-HTP, can be bought at health food stores if the body isn’t producing enough 5-HTP or serotonin on its own. Lack of serotonin is often associated with carbohydrate cravings. This is because when a person eats carbohydrates, serotonin in the brain is increased for a short time. So the body uses the 5-HTP supplement to increase serotonin in the body’s cells, which can stop the carb cravings before they ever happen.

5-HTP And Anxiety: Uses, Benefits, And Side Effects

By Sarah Cocchimiglio

Updated August 29, 2019

Reviewer Debra Halseth, LCSW

What Is 5-HTP?

5-Hyrdroxytryptophan, otherwise known as 5-HTP, or Oxitriptan, is an amino acid building block for the brain’s production of serotonin, which is a neurotransmitter that works to regulate mood and anxiety. When serotonin levels are normal, they contribute to a happy disposition and a healthy sleep cycle.

5-HTP is actually a chemical that your body produces on its own, but natural production of 5-HTP decreases as a person ages. Taking additional 5-HTP as a supplement is believed to be a way of artificially boosting the body’s production of the biochemical compound serotonin, which can have numerous health and mental health benefits.


5-HTP is considered a dietary supplement, and as such, is sold over the counter in the U.S. However, unlike many other supplements, 5-HTP does not occur naturally in foods we eat. It has been available in the U.S. without a doctor’s prescription since the mid-1990s and sold as a medicine in several European countries since the 1970s.

5-HTP is produced from the seeds of Griffonia simplicifolia, a woody shrub grown primarily in West Africa. It is used to treat a wide array of disorders and conditions, including anxiety, insomnia, depression, migraine, and more.

Doctors have long used prescription medications to manage and treat conditions like depression and anxiety. The appeal of using 5-HTP instead is that it claims to be a natural or holistic substitute, or at the very least a compliment, to prescription mental health treatments.

Potential Uses For 5-HTP

5-HTP is said to alleviate symptoms of the following conditions:

  • Obesity
  • Anxiety
  • Depression
  • Migraine and other types of occasional headache
  • Insomnia
  • Fibromyalgia
  • Attention deficit-hyperactivity disorder (ADHD)
  • Chronic headaches
  • Parkinson’s disease
  • Premenstrual syndrome (PMS)
  • Premenstrual dysphoric disorder (PMDD)
  • Binge eating
  • Seizure disorders
  • Narcolepsy
  • Sleep apnea
  • Alcohol and drug withdrawal symptoms
  • Nervous system disorders

Is 5-HTP An Effective Treatment?


5-HTP operates by increasing production of the chemical serotonin in the brain. Because inadequate serotonin levels can negatively impact many aspects of physical and mental health, including sleep, appetite and body temperature, it is believed that 5-HTP’s serotonin-boosting effects can improve certain conditions related to these health aspects.

The relief from taking 5-HTP is said to “kick in” quickly, making it more appealing than traditional prescription antidepressants and anti-anxiety medications, which can often take weeks or months before patients start to experience positive effects or relief. 5-HTP also metabolizes in the system quickly. Sources indicate that it should not be taken long term – like not for more than three months – because of potential side effects and also because its positive effects tend to dissipate over time. Taking 5-HTP is intended to be more of a short-term solution.

5-HTP is considered a holistic herbal supplement rather than a medication, so there have not been enough clinical trials involving human participants to encourage the Food and Drug Administration (FDA) to evaluate and approve it. There is not currently sufficient evidence for 5-HTP’s effectiveness for the treatment of a number of diseases and disorders such as alcoholism, Alzheimer’s disease, and schizophrenia, among others. This is not to say that it is not effective for these conditions. However, more clinical study is needed to make an official determination on the effectiveness of 5-HTP for these uses, as well as to investigate other possible side effects and dictate dosages and courses of treatment.

Should You Take 5-HTP For Anxiety?

Not much research or recent studies have been conducted on the use of 5-HTP for anxiety, so the jury is still out on its effectiveness in treating patients with anxiety. Some evidence suggests that taking 5-HTP for anxiety can reduce the effects of general anxiety. In one study, patients took 5-HTP in combination with carbidopa (a drug that increases the amount of 5-HTP entering the brain by inhibiting the enzyme that breaks down 5-HTP in the bloodstream). Some patients reported improvements in their anxiety symptoms that were comparable to patients being treated with prescription anti-anxiety medications.

Some research demonstrates that 5-HTP can promote relaxation and reduce stress and anxiety. Other research shows that taking higher amounts of 5-HTP could possibly increase anxiety symptoms and make patients feel worse. This is obviously a side effect you would not want to experience, especially if the reason you’re taking 5-HTP is to manage symptoms of anxiety.

Yet another study found that patients with panic disorder experienced reduced anxiety and panic when taking 5-HTP, although the study also found that patients who did not have panic disorder did not experience the same reduction in their symptoms of anxiety.

There is evidence, however, that 5-HTP can help you sleep better by increasing the production of melatonin, a chemical your body naturally produces that plays an important role in regulating sleep and wakefulness cycles, otherwise known as a circadian rhythm. Getting a good night’s sleep may help improve some symptoms of anxiety. In addition, 5-HTP’s serotonin-boosting qualities can have a positive effect on patients suffering from anxiety symptoms. Serotonin is linked to well-being and joy, and having more of that “happiness” chemical in the brain could reduce the severity of anxiety symptoms.

How Much 5-HTP Should You Take?

The range of doses varies widely, from 25 milligrams to 500 milligrams and up.

Starting with a low dose can minimize the risk of suffering potential side effects, especially serotonin syndrome, a condition caused by too much serotonin. Risk of adverse effects diminishes significantly when starting a course of 5-HTP at a low dose, such as 25 milligrams per day, and increasing gradually over time.


It may also help improve the quality of sleep, and reduce daytime anxiety when taken at bedtime. Gradually increasing the dose at bedtime from 50 milligrams to 200 or 300 milligrams over two to three weeks has shown to help chronically anxious patients who suffer from sleeplessness.

In general, taking low doses of 5-HTP is fairly safe, but research indicates that various levels of 5-HTP are required for the treatment of different conditions, and taking a dose that is too low may be completely ineffective. There is no specific broad-spectrum daily allowance or recommended daily dosage for 5-HTP.

So essentially, how much 5-HTP you should take depends on the reason you plan to take it. As with any other medication or supplement, you should talk to your doctor about your concerns and your plan to try taking 5-HTP. Your doctor can help you figure out a safe dosage and course of treatment.

What Are The Dangers Or Side-Effects Of 5-HTP?

The potential side effects of taking 5-HTP are many, and worrisome, including heart palpitations, abdominal discomfort, heartburn, stomach pain, drowsiness, nausea, vomiting, diarrhea, vivid dreams, shivering, agitation, insomnia, sexual dysfunction, and heart and muscle problems. It can also cause some of the very conditions it is intended to treat, including aggressiveness, restlessness, anxiety, and insomnia.

There is also some evidence that while 5-HTP may increase levels of serotonin in the brain, it may also deplete the levels of other neurotransmitters, including dopamine and norepinephrine. In this way, long-term use of 5-HTP could potentially make certain medical conditions, like generalized anxiety disorder, worse. You may want to consider taking an additional supplement that increases the amount of dopamine in the body, to counteract this side effect.

In addition, 5-HTP can interfere with other prescription or over-the-counter medications. For example, when taken in high doses, in conjunction with monoamine oxidase inhibitor (MAOI) or selective serotonin reuptake inhibitor (SSRI) antidepressants, 5-HTP can cause the serotonin-toxicity syndrome. 5-HTP may also cause interactions with Dextromethorphan, a compound found in many over-the-counter cough medicines, as well as some pain medications, like Tramadol and Demerol.

You should be cautious when taking 5-HTP in conjunction with other supplements, such as Kava, St. John’s wort, valerian, and skullcap, as the combination of these can lead to excessive sleepiness, and others, like S-adenosylmethionine (SAMe), can combine with 5-HTP to cause a dangerous spike in serotonin levels.

Another thing to consider is that since 5-HTP is not regulated by the FDA, manufacturers are not subject to the same rigorous testing and quality control that the makers of prescription drugs are required to perform. Using only USP-verified supplements can help minimize the risk of serious adverse effects related to quality control.

Pregnant and nursing women and children should absolutely not take 5-HTP without the advice of a physician.


If you’re taking 5-HTP and experience these or any other negative side effects, you should stop using it and see a doctor immediately.

You should also discontinue taking 5-HTP at least two weeks prior to undergoing any type of surgical procedure, to avoid any interaction with drugs often used during surgeries.

If you’re considering 5-HTP for anxiety, depression or other mental health condition, the safest course of action is to discuss it with your doctor first, to determine dosage and length of treatment, as well as to eliminate any potential contraindications or drug interactions. 5-HTP may work best for you alone, or in conjunction with other treatments, such as prescription pharmaceuticals, therapy, diet, and other supplements.

5-htp and social anxiety

Everyone may experience difficulties in social situations at some point in their lives. From the inability to face any form of interaction, to the panic many people feel when asked to give a speech, social anxiety is a wide-ranging and hard to diagnose condition. In a US study, people generally reported “worrying” for an average of 55 minutes a day, compared to over 300 minutes a day in people suffering from anxiety . The subject of huge amounts of ongoing research, sufferers and clinicians alike are asking for more answers. Could taking 5-htp help?

What is social anxiety disorder?

One in four people in the UK will experience mental health problems in a year . In 2013, there were 8.2 million cases of anxiety – placing it consistently within the top three mental health problems in the UK . Social anxiety disorder is characterised by an overwhelming and persistent fear of social situations. In sufferers, everyday things can provoke intense anxiety, such as speaking on the phone or shopping, causing them to fear doing or saying something inappropriate or humiliating. It’s a type of phobia that can have a disabling impact on a person’s ability to live day to day, affecting self-esteem, hampering relationships and interfering with performance at work or academically.

Social anxiety, cortisol and serotonin

Your body is wired with a complex alarm system designed to trigger when you encounter a perceived threat – such as a large dog barking. Your hypothalamus at the base of your brain springs into action, setting off a combination of nerve and hormonal signals that prompt your adrenal glands to release a surge of hormones, including cortisol and adrenaline. Adrenaline sets your heart pumping and beefs up your energy resources. Cortisol – known as the “stress hormone” – increases your blood sugar, fuels your brain and puts more substances on hand to repair tissues.

What is cortisol?

Cortisol halts anything that might not help in a fight or flight situation, altering your immune system’s responses and suppressing digestion, the reproductive system and growth while your body deals with the threat. It also communicates with the areas of your brain responsible for mood, fear and motivation. All of this is designed to return to normal once the threat has passed. However, when you feel constantly under attack – through persistent everyday stress – the alarm continues to ring. The overexposure to cortisol can disrupt most of the body’s processes, putting you at an increased risk of anxiety, depression and digestive problems, among others.

How can serotonin help?

Many recent studies have shown a link between excessive cortisol levels and lowered serotonin in the brain . Serotonin is a neurotransmitter – a chemical conduit that carries different signals between the nerve cells in the brain that influence your emotions, mood and sleep. After a message has been transmitted, serotonin is usually reabsorbed by nerve cells – known as “reuptake”. Selective serotonin repute inhibitors (SSRIs), a common type of antidepressant drug that is also widely prescribed for moderate to severe anxiety, work by blocking this reabsorption so more serotonin is on hand to transmit further messages. The theory is that by promoting more active serotonin to boost mood, the effects of excessive cortisol in the body can be counteracted.

Does 5-htp work for anxiety?

Some studies have found that 5-htp can help to relieve anxiety and boost mood, including protecting against carbon dioxide-induced panic attacks and comparable to Clomipramine (a tricyclic antidepressant) in reducing the symptoms of anxiety . 5-htp (a pre-cursor to serotonin – otherwise known chemically as 5-HT) has been used to treat depression for over 30 years. In short, when taken as a supplement, it interacts with an enzyme that strips off part of the molecule to leave serotonin that can work to counteract the effects of excessive cortisol in anxiety and improve the production of melatonin for better sleep.

brain feed’s 5-htp supplements are the smallest yet most nutrient-dense tablets available on the market. The UK’s premium supplier, brain feed put your health and wellbeing front and centre of product design, using 100% naturally derived ingredients to drive results grounded in science. Made from the highest quality extracts taken from sustainable sources – in this case, from griffonia seeds – they are twice the strength of 5-htp available from Holland & Barrett and MyProtein, helping you to relieve your anxiety in an easy-to-swallow, reliable and consistent tablet.

5-htp works on the serotonergic pathway which regulates sleep, appetite and stress so it is more than simply an option for a depressed mood. It’s great for those wishing to maintain health and enhance performance. To find out more about 5-htp .

We examined the effect of 5-HTP administrations on rhesus macaques’ (n = 6) natural viewing behavior to social (conspecific faces) and non-social (outdoor scenes and luminance matched scrambled faces) images while their eye positions were tracked with high spatial and temporal acuity (Fig. 1a). On separate days, we collected CSF samples 1 h after acute delivery of saline, 20 mg/kg, and 40 mg/kg 5-HTP to examine how 5-HTP influences central serotonergic function and to provide insight into the mechanism by which 5-HTP modulates attention.

Exogenous 5-HTP increases CSF 5-HTP and serotonin concentrations and modulates autonomic arousal

To assess physiological arousal, we quantified the size of the pupil during the 300 ms fixation period where only the luminance controlled white fixation square appeared on the screen. We found that 5-HTP did impact the size of the pupil (Fig. 1d, F (2, 3) = 46.35, P < 0.001, ANOVA). Subjects had a significantly more constricted pupil during 20 mg/kg (P < 0.001, Tukey) and 40 mg/kg 5-HTP sessions (P < 0.001) than saline sessions, indicating a consistent physiological effect of 5-HTP. Our CSF and pupil results indicate that i.m. 5-HTP administrations effectively increased central concentrations of 5-HTP and serotonin and impacted the parasympathetic system.

Baseline behavior underlies the direction and magnitude of 5-HTP’s effects on attention

We used looking duration as a proxy measure to investigate how 5-HTP modulates attention to images (Fig. 1a). We first examined looking duration, for all animals, to all images, during saline, 20 mg/kg, and 40 mg/kg sessions. When all animals were analyzed together, drug dose did not impact raw looking duration (Fig. 2a, F(2, 287) = 1.12, P = 0.33). However, 5-HTP significantly increased looking duration in three subjects, those that exhibited low baseline attention during the eight saline sessions (average baseline looking of 1572.94 ± 460.85 ms), but significantly decreased looking duration in the other three subjects, those that exhibited high baseline attention during the eight saline sessions (average baseline looking of 2672.72 ± 362.16 ms, Fig. 2b). To account for this bi-directional effect, we calculated the absolute value of the percent change in looking duration from saline and found that 5-HTP significantly modulated looking duration across animals (Fig. 2c, F(2, 287) = 23.03, P < 0.01). We next investigated whether this diversity in 5-HTP’s effect on attention is related to differences in baseline attention by quantifying each subjects’ percent change from saline in looking duration due to eight sessions each of 20 mg/kg and 40 mg/kg 5-HTP. We found that baseline looking duration was negatively correlated with 5-HTP-induced changes in looking duration (Fig. 2d, r = −0.81, P < 0.01). To ensure that the observed effect was indeed due to 5-HTP differentially modulating the looking behavior across individual animals and not due to a regression to the mean phenomenon, we randomly shuffled the labels associated with each session for each animal (saline, 20 mg/kg, or 40 mg/kg 5-HTP) and re-ran the above analyses 1000 times to create a null distribution for what could be expected if 5-HTP was not truly impacting looking duration but instead was due to a regression to the mean. In these analyses, all the percent changes in looking duration were far outside the range of the observed data (P = 0.02, t-test), and the shuffled data exhibited no correlation (Fig. 2b, c lower panels, r = −0.14, P = 0.66, Pearson’s). Thus, acute 5-HTP increased looking duration in animals with low baseline attention but decreased looking duration in animals with a high baseline attention.

Fig. 2

The direction and magnitude of 5-HTP’s effects on attention are rooted in baseline behavior. a 5-HTP causes a bi-directional change in looking duration. 20 mg/kg (green) and 40 mg/kg (red) 5-HTP increases looking duration in animals with low baseline looking (dashed line) during saline sessions and decreases looking duration in high baseline looking animals (solid line). b (Top) Average looking duration for low and high baseline animals (grouped solid and dash lines from a). (Bottom) Average looking duration for low and high baseline animals after shuffling the drug labels within each animal. c 5-HTP significantly increases the magnitude change, the absolute value of the percent change, in looking duration relative to saline. d (Top) Baseline looking duration to images negatively correlates with percent change in looking duration due to 5-HTP (green, 20 mg/kg; red, 40 mg/kg). (Bottom) The average correlation from the shuffled data. In a, c, d, each shape represents an individual subject’s data

Animals exhibit different levels of task engagement, but not motivation to acquire juice

We next characterized whether all animals were equally engaged in the task to determine if differences in attention to images were related to differences in task motivation, both to acquire juice and also to view images. We assessed motivation to acquire juice by quantifying the number of trials completed per session for high and low baseline attention animals. Neither baseline attention (F(1,138) = 2.55, P = 0.11, ANOVA) nor drug dose (F(2,143) = 0.91, P = 0.41) significantly affected the number of trials completed per session, indicating that animals completed the same number of trials, thereby earning the same amount of juice, regardless of baseline attention or drug dosage.

We then assessed anticipatory looking between trials and used this measure as a proxy for task engagement, that is an animal’s motivation to initiate another trial quickly and view more images . We quantified anticipatory looking by calculating the percentage of trials during which subjects looked at the region near the fixation during the inter-trial interval when the screen was blank prior to the start of a new trial (See Supplementary Materials and Methods). The magnitude change in anticipatory looking was impacted by drug dose (saline, 20 mg/kg, and 40 mg/kg 5-HTP) (F(1, 131) = 8.93, P < 0.01, ANOVA). Notably, baseline anticipatory looking (during saline sessions) was negatively correlated with 5-HTP-induced changes in anticipatory looking (Fig. S1A, r = −0.72, P < 0.01). Low baseline attention animals exhibited lower task engagement than high baseline attention animals during saline sessions; 5-HTP increased engagement in low baseline animals, and decreased engagement in high baseline animals (Fig. S1B).

Social specificity of 5-HTP’s effect is related to differences in baseline attention to social and non-social images

Social stimuli are inherently more salient than non-social stimuli. Animals overall looked at social images longer than non-social images (F(1, 287) = 15.31, P < 0.001, ANOVA, Fig. S2), and 5-HTP overall modulated looking to social images more than non-social images (Fig. 3a, F(1, 287) = 13.51, P < 0.001, see Fig. S3 for raw data for each subject). When we examined if variation in 5-HTP’s social specificity was predicted by baseline behavior, the difference between looking duration to social and non-social images at saline was negatively correlated with the difference in 5-HTP-induced changes in looking duration to social and non-social images (Fig. 3a, r = −0.72, P < 0.01, Pearson’s). Thus, for individuals who looked longer at social than non-social images at baseline, 5-HTP decreased looking to social more than to non-social images. By contrast, for individuals who looked longer at non-social images at baseline, 5-HTP instead increased looking to social more than to non-social images. We next investigated whether the same animals that spent less time looking at social stimuli at baseline were also the animals that exhibited baseline lower attention to all images. We found that indeed looking duration to all images were positively correlated with the average difference between looking duration to social and non-social images during saline sessions (r = 0.84, P = 0.04) indicating that animals who looked at all images for a longer period during saline sessions also exhibited a longer relative looking duration to social images during saline sessions. This provides further support that baseline differences in attention predict the manner in which 5-HTP modulates attention.

Fig. 3

5-HTP differentially modulates attention to facial features. a The difference between looking duration to social and non-social images is negatively correlated with the difference in percent change from saline, due to 20 mg/kg (green) or 40 mg/kg 5-HTP (red), in looking duration to social and non-social images. (Right) The average difference in percent change in looking duration to social images and percent change in looking duration to non-social images for low and high baseline animals. The inset shows the raw looking duration to social (filled bars) and non-social images (open bars) for low and high baseline animals. b The percent change from saline due to 5-HTP in the probability of looking at the eye region during image presentation is negatively correlated with baseline probabilistic looking to the eye. (Right) Average time plots for low and high baseline animals for 5-HTP’s effect on attention to the eyes. c The percent change from saline due to 5-HTP in the probability of looking at the mouth region is negatively correlated with baseline probabilistic looking to the mouth. 5-HTP increases attention towards the mouth in low baseline animals but decreases attention towards the mouth in high baseline animals. (Right) Average time plots for low and high baseline animals for the bi-directional effect on attention to the mouth. In a-c, each shape represents an individual subject’s data

5-HTP bi-directionally modulates attention to the eyes and mouth

We next focused on the mouth and eye regions of the face to test if 5-HTP modulates attention to salient face regions differently depending on gaze directions (directed vs. averted) and facial expressions (threat vs. fear grimace vs. lip smack vs. neutral). Raw looking duration and percent change in looking duration due to 5-HTP for the face region of each social category are shown in the Supplementary Materials Results and Figs. S4 and S5. We calculated the percentage of trials that subjects looked within the eye or mouth regions to obtain the magnitude change, absolute value of the percent change, in probabilistic looking to the eyes and mouth due to 5-HTP. This allowed us to examine differences in 5-HTP’s effect on probabilistic looking due to stimulus monkey gaze direction and facial expression.


The magnitude change in probabilistic looking to the eyes was impacted by drug dose (Fig. 3b, F(2, 1024) = 31.37, P < 0.001, ANOVA, with a stronger effect of 40 mg/kg compared to 20 mg/kg 5-HTP, P < 0.001, Tukey), gaze direction (directed vs. averted) (F(1, 1024) = 7.28, P < 0.01, with a larger effect for faces with direct gaze), as well as facial expression (threat vs. fear grimace vs. lip smack vs. neutral) (F(3, 1024) = 18.03, P < 0.001, larger for expressive than for neutral expressions, all P < 0.001). These results indicate that 5-HTP differentially influences attention to the eyes based on the gaze direction and the saliency of the facial expression of the stimulus monkeys. We next asked whether 5-HTP’s effects on attention to the eyes are related to differences in baseline attention to the eyes. Baseline looking to the eye region was negatively correlated with 5-HTP-induced changes in looking to the eye region (Fig. 3b, r = −0.60, P = 0.04, Pearson’s). 5-HTP thus increased attention to the eyes in animals with low baseline attention but decreased looking duration in animals with high baseline attention.


The magnitude change from saline in probabilistic looking to the mouth was also affected by drug dose (Fig. 3c, F(2, 1054) = 30.53, P < 0.001, with a stronger effect of 40 mg/kg compared to 20 mg/kg 5-HTP, P < 0.001) and facial expression (threat vs. fear grimace vs. lip smack vs. neutral) (F(3, 1054) = 2.95, P = 0.03, with only fear grimaces as larger than neutral expressions after correcting for multiple comparisons, P = 0.02), but not gaze direction (directed vs. averted) (F(1, 1054) = 1.63, P = 0.2). These results indicate that 5-HTP differentially influenced attention to the mouth based on whether the facial expression relied on salient mouth features to communicate social signals. We again asked whether 5-HTP’s effects on attention to the mouth are related to differences in baseline attention, and found that baseline looking to the mouth was negatively correlated with 5-HTP-induced changes in looking (Fig. 3c, r = −0.68, P = 0.02). 5-HTP thus increased attention to the mouth in animals with low baseline attention but decreased looking duration in animals with high baseline attention.

Taken together, these results indicate that 5-HTP increases attention to informative regions of the face for animals with low baseline attention to these regions, but decreases attention to the eyes and mouth for animals with high baseline attention. Overall 5-HTP thus modulates attention to salient facial features that convey important social information and the direction and magnitude of 5-HTP’s effects can be predicted by baseline differences in how individuals allocate attention to the eyes and mouth.

Baseline central serotonergic function predicts the direction and magnitude of 5-HTP’s effects on attention

To examine the relationship between central serotonergic processing and looking behavior, we first tested if the amount of 5-HTP that crossed the blood-brain barrier would predict differences in attention during 5-HTP sessions. Central concentrations of 5-HTP after receiving 20 mg/kg and 40 mg/kg injections of 5-HTP were positively correlated with individuals’ average looking durations during the sessions associated with each drug dose (Fig. 4a, r = 0.73, P = 0.016, Pearson’s correlation), suggesting that the amount by which 5-HTP injections modulate central concentrations of 5-HTP did in fact influence how long individuals looked at images.

Fig. 4

Serotonergic function predicts how 5-HTP modulates looking behavior. a Central concentrations of 5-HTP after receiving 20 mg/kg (green) and 40 mg/kg (red) 5-HTP injections are positively correlated with the average looking duration to social images during the 5-HTP sessions associated with each drug dose. b Central levels of 5-HTP at saline correlate with percent change in looking duration from saline due to 5-HTP. c Baseline central levels of serotonin (5-HT) correlate with the percent change in looking duration from saline due to 5-HTP. d Baseline central 5-HIAA/serotonin (5-HT) ratios correlate with the percent change in looking duration from saline due to 5-HTP. In a-d, each shape represents an individual subject’s data

We next determined if central concentrations of serotonergic compounds were related to 5-HTP’s observed bi-directional effects on attention by comparing 5-HTP-induced changes in attention to baseline CSF concentrations of 5-HTP and serotonin. Interestingly, baseline 5-HTP concentrations were positively correlated with the percent change in looking duration due to 5-HTP (Fig. 4b, r = 0.81, P < 0.01), suggesting that baseline levels of 5-HTP predict the manner in which attention is modulated by 5-HTP. Concentrations of baseline serotonin were also positively correlated with the percent change from saline in looking duration due to 5-HTP (Fig. 4c, r = 0.78, P = 0.02), providing more evidence that concentrations of central serotonergic compounds, even prior to 5-HTP manipulations, influence, in part, how 5-HTP will influence attention. In fact, baseline tryptophan and HVA concentrations were also correlated with the percent change in looking duration due to 5-HTP (tryptophan: r = 0.77, P = 0.01; HVA: r = 0.80, P < 0.01), while baseline 5-HIAA concentrations trended to be correlated with the percent change in looking duration (r = 0.62, P = 0.05). However, baseline concentrations of neither norepinephrine nor tyrosine were correlated with the percent change in looking duration due to 5-HTP (norepinephrine: r = 0.56, P = 0.15; tyrosine: r = 0.50, P = 0.14). These results further suggest that baseline concentrations of serotonergic related compounds are related to 5-HTPs effects on attention and that dopaminergic activity could also play a role.

Despite this converging evidence, we were puzzled that animals with low baseline attention exhibit higher baseline concentrations of 5-HTP and serotonin compared to high baseline attention animals. We conjectured that this discrepancy might be due to differences in the rate of serotonin turnover. While our experiment did not allow us to provide direct evidence, we analyzed a metric that has been used to estimate turnover in tissue samples, the 5-HIAA/serotonin ratio. CSF 5-HIAA/serotonin ratios at baseline were inversely correlated with the percent change in looking duration (Fig. 4d, r = −0.82, P = 0.03), indicating that animals with lower baseline attention might exhibit lower serotonergic turnover compared to animals with higher baseline attention. In addition, the central ratio of 5-HIAA to serotonin also correlated with average difference between looking duration to social and non-social images during saline sessions (r = 0.98, P = 0.02) indicating that a higher baseline 5-HIAA/5-HT ratio predicts a larger preference for social images over non-social images at baseline.

In day to day life most people will experience anxiety. It stems from an innate reaction called our fight-or-flight response, which is a response that attempts to protect us from harm.

Anxiety can be ….

Caused by minor every day hassles such as missing your train or handing in a project at work. Alternatively it can be caused by large and life changing events such as such as moving house or getting married.

Anxiety can be irrational or rational. An example of rational anxiety is your first day at a new job. An example of irrational anxiety is not being able to touch a door handle in the belief it will make you severely unwell .

Symptoms of anxiety will effect a person both physically and mentally. Psychological symptoms include:

  • Feeling nervous
  • Feelings of impending doom
  • Dwelling on negative experiences
  • Feeling as if someone is constantly judging you
  • Restlessness

Psychological symptoms can go on to cause physical manifestations. Physical Symptoms include:

  • Nausea, and an unsettled stomach
  • Sweating
  • Increased heart rate
  • Difficulty sleeping
  • Panic attacks

There are number of different disorders classified under the term “Anxiety” such as Generalised anxiety disorder (GAD) Panic Disorder (PD), Phobias, Obsessive compulsive disorder (OCD) and Post Traumatic Stress Disorder (PTSD) .

What is the cause of Anxiety Attacks?

One manifestation of anxiety called Panic Disorder (PD) has be extensively studied and has found a prominent link between Serotonin/5-HTP and the disorder. It has been shown conversely by medication that low levels of Serotonin causes high levels of anxiety and attacks. In addition, a 2002 study found that decreased level of Tryptophan, the precursor of 5-HTP and Serotonin caused a decrease in direct Serotonin production and led to an increase in panic disorder attacks .

There are many ways to reduce anxiety including medication or psychotherapy. In addition, anxiety can be reduced by over-familiarising yourself with the object/person/situation that causes the anxiety in the first instance. Lastly, focus on your well-being through nutrition, exercise and supplements.

One supplement that is particularly popular with anxiety sufferers is 5-HTP (5-Hydroxytryptophan). 5-HTP has been clinically proven to decrease physical and psychological symptoms of anxiety . Tryptophan is a precursor to 5-HTP which is a precursor to Serotonin that as we know calms the flight-or-fight response . One study found that taking 5-HTP was almost as effective as Clomipramine (synthetic anxiety medication).

How to take it?

5-HTP is advised to be taken from 50mg to 200mg, however a dosage of up to 300mg can be effective and non-toxic. Always be concious of the amount you are dosing, especially when using 5-HTP powder. Approximately 70% of an oral dosage will reach the blood stream and thus be effective. Advice states that you should start off at a lower dosage and build-up until you reach the one that is most effective for you. Do not exceed the upper limits of 5-HTP. You are advised to only take it for a a few months as it is not long term solution.

Just because it is natural doesn’t necessarily mean it’s safe for all. There are very few cases of side effects such as aggressiveness, headaches, stomach pains or heartburn, if these do occur cease taking 5-HTP. The best way to take 5-HTP is alongside a Vitamin B6 Tablet as this is known to increase 5-HTPs conversion efficiency to Serotonin .

Anxiety can take a grip on life as you know it, altering your cognitions and feelings, this is no way to live. 5-HTP is a well-tested and popular natural supplement that can help reduce anxiety and normalise life again. Take hold of your life today!

5-HTP the Womanly Antidepressant Cofactor that could Kill You…

This is a very dangerous condition caused by combining two or more serotonergic supplements or drugs, such as…

  • Selective serotonin reuptake inhibitor(SSRI)
  • Serotonin-norepinephrine reuptake inhibitor(SNRI)
  • Monoamine oxidase inhibitor(MAOI)
  • Tricyclic antidepressants (TCAs)
  • Amphetamines
  • Pethidine(meperidine)
  • Tramadol
  • Dextromethorphan
  • Buspirone
  • L-tryptophan
  • St. John’s Wort
  • Triptans
  • Ecstasy
  • Metoclopramide
  • Ondansetron
  • Or cocaine

You would not want to take these drugs within 24 hours of each other. Particularly combining the SSRIs or the SNRIs with 5-HTP. It causes a number of very undesirable symptoms up to and including death.

An Anti-Nootropic?

A Dutch placebo-controlled study indicated 5-HTP may actually impair cognition, from it’s abstract

Cognitive impairment has repeatedly been described in bipolar disorders… Serotonin (5-hydroxytryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of patients…
In all groups, impaired memory and psychomotor performance significantly. In conclusion, cognitive deficits in following may reflect a central 5-HT vulnerability in frontal brain areas. Independent of , cognitive deficits in provide evidence for a trait marker for .

An Ohioan Biohacker explains:

“Simply put, the more of the tryptophan metabolite kynurenic acid floating around in your body the more antagonism on the a7 nicotinic acetylcholine receptor, glycine site of the NMDA receptor, and enhanced risk of certain metabolic disorders.”

5-HTP is what tryptophan metabolizes into and there is a significant amount of anecdotal reports complaining about how it causes brain fog, tiredness lack of energy or motivation. I won’t go so far as to call it an Anti-Nootropic as it does help some seriously depressed people but I don’t expect much of a performance enhancement effect from it.


A double-blind, placebo-controlled 2010 Californian study evaluated a stack of 5-HTP, Gaba and Valerian for 18 patients with sleep disorders.

Sleep latency and duration of sleep were measured by daily questionnaires. Sleep quality was measured using a visual analog scale. Autonomic nervous system function was measured by heart rate variability analysis using 24-hour electrocardiographic recordings…
The difference between the active and placebo groups was significant (P = 0.01). Ease of falling asleep, awakenings, and am grogginess improved. Objective measurement of parasympathetic function as measured by 24-hour heart rate variability improved in the active group compared with placebo.

So Gaba (maybe Phenibut), 5-HTP and Valerian is a sleep cocktail worth trying!

One Biohacker reported:

“My sleep is so deep that I oversleep, and I also have began to feel very drained of energy.”

Panic Attacks

Interestingly 200 milligrams protects from panic attacks for those that are susceptible to acute anxiety. From a Dutch study of 24 people suffering from panic disorder and 24 otherwise healthy people:

“L-5-Hydroxytryptophan significantly reduced the reaction to the panic challenge in panic disorder patients, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo. No such effect was observed in the healthy volunteers. L-5-Hydroxytryptophan acts to inhibit panic, which supports a modulatory role of serotonin in panic disorder.”

An Estonian study confirmed this finding

“Further analysis by gender revealed that females in the 5-HTP group had a significantly lower panic rate and intensity of cognitive symptoms whereas, in males, the effect of 5-HTP was limited to lowering the intensity of somatic panic symptoms. Thus, an increased availability of 5-HT may have a gender-dependent protective effect in CCK-4-induced panic.”

For Heartbreak

Humorously, a 2010 Italian study was conducted to see if 5-HTP could help assuage the heartbreak of young lovers:

The subjects were evaluated at baseline, at 3 weeks and at the end of the 6-week trial using an adapted version of the Seiffge-Krenke’s Problem Questionnaire. BDNF and platelet serotonin content were determined at baseline, at 3 weeks, and after the completion of the 6-week trial…
Our data suggest that direct modulation of the serotonergic system may have use for the treatment of psychological suffering associated with unreciprocated romantic love.

It’s not a great study because it was not placebo-controlled and in the study itself the helpful effect of the 5-HTP did not help after 6 weeks, but perhaps the young Italians simply found new lovers after 6 weeks.

Weight Loss

As a downstream effect of its mood enlightening, it helps people lose weight by regulating appetite.
From an Italian study that gave diabetic patients 750 milligrams of 5-HTP

“25 overweight non-insulin dependent diabetic outpatients were enrolled in a double-blind, placebo-controlled study, and randomized to receive either 5-HTP (750 mg/d) or placebo for two consecutive weeks, during which no dietary restriction was prescribed…
20 patients (nine from the 5-HTP group and 11 from the Placebo group) completed the study. Brain tryptophan availability in diabetic patients was significantly reduced when compared to a group of healthy controls. Patients receiving 5-HTP significantly decreased their daily energy intake, by reducing carbohydrate and fat intake, and reduced their body weight.”

An older Italian study suggested that it promoted anorexia…

“The administration of 5-hydroxytryptophan resulted in no changes in mood state but promoted typical anorexia-related symptoms, decreased food intake and weight loss during the period of observation.”

…So people struggling with anorexia may want to avoid 5-HTP. The study subjects were obese women so presumably, a little anorexic behavior would not be a bad thing.

A follow-up study was done by the same researchers confirming that it’s weight loss mechanism is basically that it decreases the desire to eat (satiety — that’s your new word of the day!)

“The study was double-blinded and was for two consecutive 6-wk periods. No diet was prescribed during the first period, a 5040-kJ/d diet was recommended for the second. Significant weight loss was observed in 5-HTP-treated patients during both periods. A reduction in carbohydrate intake and a consistent presence of early satiety were also found. These findings together with the good tolerance observed suggest that 5-HTP may be safely used to treat obesity.”

What’s interesting is it says that the diet the subjects were on did not matter much. Simply decreasing the desire to eat led, generally to them losing weight.

Alcohol Withdrawal

In combination with some other Nootropics it can be helpful for alleviating alcoholic withdrawal. From a 2011 Croatian study:

“20 patients suffering from alcohol addictions starting a detoxification therapy have been included in a prospective, randomized, double blind study…
The use of food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan alleviates the withdrawal symptoms and causes a rise in CD4 lymphocyte population, but it dose not affect the serum cortisol levels, which are probably more affected by liver inflammation and the liver restitution.”

So maybe worth trying for those struggling with alcoholism.

Some other Nootropics that may help with Alcoholism and alcohol withdrawal are Tianeptine, Piracetam, and Niacin.

Mechanism of Action

It does cross the blood-brain barrier, from a paper that appeared in Alternative Medicine Review:

“5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin.”


It comes from the African plant Griffonia Simplicifolia.

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