Believe it or not, serotonin can act both as a neurotransmitter and a hormone. It is important for both mental and physical wellbeing. Serotonin can affect everything from mood and behavior to gut and heart health to blood vessel function. Low levels of serotonin have been associated with mood disorders, migraines, and gut issues. Read on to discover factors that may boost serotonin levels naturally.
What is Serotonin?
Serotonin is an important signaling molecule best known as the “happiness neurotransmitter” or the “happiness hormone.” It plays an important role in the brain, where its main job is to transmit messages between nerve cells. According to some scientific theories, serotonin is involved in all aspects of human behavior [1, 2].
However, brain serotonin comprises less than 2% of the total serotonin found in our bodies. Most serotonin (over 90%) is actually made, stored, and released by the gut. In addition, about 5-8% of serotonin is stored in platelets circulating in the blood [1, 3, 4].
- Mood and emotions
- Movement (motor function)
- Sleep-wake cycle
- Body temperature
- Bowel movements
- Various gut functions
- Blood clotting (platelet aggregation)
- Constriction and relaxation of blood vessels
- Immune responses
- Bone development
- Heart function
- Reproductive function
- Pain perception
What Does It Do?
Discovered in the 1940s, serotonin, also known as 5-hydroxytryptamine or 5-HT, plays pivotal roles in mood, behavior, gut, and overall optimal body function (homeostasis). Imbalances in serotonin have been linked with symptoms that may interfere with mental and physical health and possibly impair the quality of life [6, 7, 8].
According to some hypotheses and limited research, increasing serotonin levels may help with anxiety, depression, migraines, and constipation-predominant irritable bowel syndrome. However, large-scale studies are needed [6, 7, 8].
Production and Removal
Specific bacteria in the human digestive tract can boost serotonin production in the gut. Gut flora actually balances tryptophan metabolism (via the kynurenine pathway), influencing the amount of L-tryptophan available for making serotonin [11, 12].
Serotonin made in the gut cannot cross the blood-brain barrier. That is why brain cells must produce their own serotonin, from either L-tryptophan or 5-hydroxytryptophan (5-HTP), a by-product of L-tryptophan [13, 14].
The serotonin that gets released into the blood gets either taken up by platelets or rapidly broken down in the liver and lungs by enzymes called monoamine oxidase (MAO-A) and aldehyde and alcohol dehydrogenase .
When we talk about serotonin-associated disorders, it‘s important to know that these disorders are not necessarily due to serotonin levels or production as such. They can stem from issues with serotonin reuptake or the availability of certain serotonin receptors. There are over 15 different receptor types discovered to date, including the well-known 5-HT1A, 5-HT2A, and 5-HT2C [16, 17, 18].
Additionally, the majority of studies covered in this article deal with associations only, which means that a cause-and-effect relationship hasn’t been established.
For example, just because depression has been linked with low serotonin in certain brain areas doesn’t mean that depression is caused by low serotonin. Data are lacking to make such claims. Also, even if a study did find that low brain serotonin contributes to depression, serotonin levels are highly unlikely to be the only causative factor. Complex disorders like depression always involve multiple possible factors – including brain chemistry, environment, health status, and genetics – that may vary from one person to another.
- Mental health disorders, including depression, anxiety, aggression, obsessive-compulsive behavior, substance abuse, and schizophrenia
- Irritable bowel syndrome (IBS)
- Heart disease
Additionally, scientists believe serotonin connects the gut microbiome with the brain – forming the so-called “gut-brain axis.” Decreased diversity and stability of beneficial gut bacteria has been linked with serotonin-related health issues, especially in the elderly [21, 22, 23].
A meta-analysis of 53 studies discovered that patients with a family history of major depressive disorder (MDD) or those diagnosed with MDD but now in remission, who were tryptophan- or tyrosine-depleted experienced low mood. No difference was observed in healthy individuals .
An imbalance in serotonin, dopamine, and norepinephrine may play a role in bipolar disorder. It has been proposed that the combined low levels of these 3 neurotransmitters, and not serotonin alone, may contribute to mood disorders .
In the pineal gland, serotonin is used to make melatonin, a hormone that synchronizes the body’s “biological clock” or circadian rhythm. When serotonin is low, that limits the amount of melatonin that can be made in the body, potentially interfering with the sleep-wake cycle .
38 Factors that May Increase Serotonin Naturally
When to see a doctor
If your goal is to increase serotonin to improve your mood-related issues – including those of depression or anxiety – it’s important to talk to your doctor, especially your mood is significantly impacting your daily life.
Major mood changes, such as excessive sadness, persistent low mood, euphoria, or anxiety, are all reasons to see a doctor.
Your doctor should diagnose and treat the condition causing your symptoms.
Remember that the existing evidence does not suggest that low brain serotonin causes mood disorders. Complex disorders like depression always involve multiple possible factors – including brain chemistry, environment, health status, and genetics – that may vary from one person to another.
Additionally, changes in brain chemistry are not something that people can change on their own with the approaches listed below. Instead, the factors listed here are meant to reduce daily stress and support overall mental health and well-being.
Therefore, you may try the additional strategies listed below if you and your doctor determine that they could be appropriate. Read through the approaches listed here and discuss them with your doctor before trying them out. None of these strategies should ever be done in place of what your doctor recommends or prescribes.
1) Stress Reduction
Our bodies release cortisol when stressed. Cortisol likely decreases serotonin levels in the body by increasing serotonin reuptake. Some scientists hypothesize that too much cortisol can impair mental health. That is why reducing mental stress can help balance cortisol levels and increase serotonin .
Many of the lifestyle changes below can be used to decrease stress.
2) Mood Improvement
Serotonin impacts our mood, but mood also affects serotonin production. Studies using brain imaging (PET), showed that brains of people who are happy produce more serotonin than brains of people who are sad .
Therefore, engaging in activities and doing things that make you happier can help boost serotonin production.
In addition, studies show that social interactions also influence serotonin levels. Spend more time with people who make you feel good in general .
However, don’t get discouraged if you can’t “make yourself feel happy.” Mental health and moods are complex and altering your mood is not simple nor is it always a good idea. Consciously trying to reframe some excessively negative thoughts in a positive light may be beneficial in some cases. In other cases, consulting a therapist is necessary.
Psychotherapy or counseling may change behavior, thinking patterns, brain chemistry, and possibly even increase serotonin activity (by increasing serotonin receptors). Psychotherapy is usually recommended together with pharmacotherapy in people with mood disorders .
In a study of 23 patients with depression who participated in psychotherapy for 4 months, therapy significantly increased serotonin activity and improved symptoms of depression .
Fatigue, as a result of exercise, increases the amount of tryptophan that can cross the blood-brain barrier (by decreasing BCAA levels) and thereby boosts serotonin production. The psychological benefits of physical exercise can be more readily achieved with consistent aerobic exercise training [30, 31, 32, 33].
Mice that ran on treadmills had higher levels of serotonin compared to mice that remained inactive. Brain tryptophan remained high even after exercise .
5) Getting More Sun
According to one hypothesis that has yet to be proven, our modern way of life – in which we spend a lot of time indoors – may be depleting our serotonin levels, thereby making us more vulnerable to mood disorders .
Therefore, going outside and spending more time in the sun on a regular basis may be a healthy way to boost your serotonin levels.
6) Yoga and Meditation
A review of over 200 peer-reviewed RCTs, clinical trials, and meta-analyses studying complementary and alternative medicine suggest that yoga and meditation may help uplift mood and improve symptoms of mild, moderate, and treatment-resistant depression when used as an add-on to standard care .
In fact, meditation activates many parts of the brain important for understanding the self, emotions, problem-solving, adaptability, and increasing awareness. Serotonin plays a role in wakefulness, along with other neurotransmitters, which are all raised in meditators according to some studies [45, 46, 47].
Thirty minutes of yoga and breathing exercises improved mood in a study of 71 healthy adults .
7) Music Therapy
However, human data are lacking. Rats exposed to melodic music (e.g. Mozart’s sonatas) released more serotonin in their brains .
8) Dance Therapy
A study of 40 students around the age of 16 who participated in dance movement therapy had increased blood serotonin levels compared to the control group .
Dance therapy may be sometimes recommended as a complementary behavioral approach to pharmacotherapy and psychotherapy in some people with mood disorders.
Tryptophan is the amino acid building block for serotonin. Tryptophan is not produced by the body, so it must be taken in through diet.
Current research shows that unlike purified tryptophan, consuming tryptophan-rich foods does not necessarily increase brain serotonin. That’s because tryptophan-rich foods, such as meat, dairy, fruits, and vegetables, also contain many other amino acids. Tryptophan has to compete with these other amino acids for transport across the blood-brain barrier [33, 51].
On the other hand, lack of dietary tryptophan (compared to other amino acids) may lead to lower blood and brain tryptophan levels, decreasing serotonin production. Increased BCAAs may also lower tryptophan and serotonin, as well as dopamine in the brain. This may be relevant for people who take protein powders to enhance exercise performance [52, 53].
9) Healthy Carbs
Increasing the intake of healthy, complex carbs might be a good idea. Some examples of healthy carbs include whole fruits, vegetables, legumes, and nuts.
However, avoid unhealthy and refined carbs like sugar and white bread in your diet. Refined carbs have a plethora of negative health effects.
Make sure to speak with your doctor before taking any supplements. Make sure to let them know about any prescription or over–the–counter medication you may be taking, including vitamins and herbal supplements.
This is particularly important if you are already taking medications (such as antidepressants) or supplements that may increase serotonin levels. Interactions or incorrect dosing may cause serotonin syndrome, a serious condition that results from too much serotonin in the body.
If you and your doctor agree that supplementing is a good idea, choose products made by a trusted and reliable manufacturer.
Remember that dietary supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective.
Some research suggests these supplements may help increase serotonin and support mood balance:
10) L-Tryptophan and 5-HTP
In the body, L-tryptophan is used to make 5-HTP from which serotonin is made. Limited research suggests that taking L-tryptophan may raise plasma serotonin, improving cognitive, motor, or gut issues in those who are deficient [56, 57].
A protein called alpha-Lactalbumin from milk contains more tryptophan than many other proteins. In a study of 18 individuals, 12 grams of alpha-Lactalbumin increased the amount of tryptophan in blood plasma by 16% after 90 minutes .
In a pilot study of 13 female patients experiencing premenstrual syndrome (PMS), 6 grams of L-tryptophan taken daily for 14 days improved mood, irritability, difficulty sleeping, and carbohydrate craving .
Tryptophan can be purchased in the form of L-tryptophan supplements. 5-HTP (5-hydroxytryptophan) supplements are also available. It is important to note that 5-HTP is not the same as 5-HT, which is the chemical name for serotonin. 5-HTP freely crosses the blood-brain barrier (serotonin itself does not) to be converted into serotonin .
In the digestive tract, probiotics restore the gut microbiome and influence the gut-brain axis. Gut bacteria are important because they can produce tryptophan, from which serotonin is made. Neurological disorders, such as Parkinson’s disease, have been linked to less diverse or fewer gut bacteria in some studies [61, 62].
In one study, an 8-week probiotic regimen (2.0 x 109 CFU/g of Lactobacillus helveticus and 2.0 x 109 CFU/g of Bifidobacterium longum) increased tryptophan levels in 110 individuals with depression. Increased tryptophan can, theoretically, increase serotonin production [63, 13].
A probiotic (Bifidobacteria infantis) given to rats for 14 days raised levels of blood tryptophan .
12) Vitamin D
Vitamin D activates an enzyme that converts tryptophan into serotonin. If vitamin D levels are low, our brains make less serotonin. Thus, increasing vitamin D intake may increase serotonin levels, supporting mental health [42, 43].
A cohort study of over 9k subjects suggested that taking vitamin D supplements during the first year of life was correlated with a 77% reduced risk of schizophrenia. In other words, preventing low vitamin D levels early in life may reduce the chance of having schizophrenia later in life, though large-scale studies are needed to verify this theory .
13) Omega-3 Fatty Acids
While vitamin D helps neurons make serotonin, the omega-3 fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), help neurons release serotonin and improve its activity (increasing serotonin receptor sensitivity) .
According to some researchers, inadequate omega-3 fatty acid intake may increase susceptibility to psychiatric illnesses, including depression. However, a clear link hasn’t been established .
In a study of 49 patients that repeatedly self-harm themselves, 1.2 grams of EPA and 0.9 grams of DHA capsules daily for 12 weeks reduced suicidal thinking by 45% and depression by 30%. Nonetheless, this study was limited by its small sample size and short duration .
An observational study of 256,118 Japanese participants discovered that people who ate fish daily had lower rates of suicidal thoughts compared to people who did not eat fish daily. In another observational study of 1,767 Finnish subjects, consuming fish less than twice a week was associated with a higher risk of depression and suicidal thinking [68, 69+].
Reduced intake of both EPA and DHA by pregnant rats resulted in less production, storage, release, and activity (receptor function) of serotonin in the brains of their offspring. Serotonin was not only reduced in the mothers’ brains but also its availability and production were reduced by (65% and 29%, respectively) in the brains of newborn rats .
14) St. John’s Wort
St. John’s Wort is a popular medicinal plant (Hypericum perforatum) used as a supplement for mild depression. However, according to the National Center for Complementary and Alternative Medicine (NCCIH), the results of studies on the effectiveness of St. John’s wort for depression are mixed .
Importantly, clear evidence shows that St. John’s wort can interact in dangerous, potentially life-threatening ways with many medicines. Never take this plant without consulting a doctor first .
In a review (of 35 studies) of 6,993 patients with depression, St. John’s Wort standalone therapy improved only mild to moderate symptoms of depression. However, the authors pointed out the low quality of the included studies and inconsistency in effectiveness. The typical dose is 300 mg of the extract 3 times per day for at least 4 weeks .
15) S-Adenosyl Methionine (SAM-e)
It is a naturally occurring compound that plays a role in methylation and energy breakdown. Limited data suggests it may reduce symptoms in some people with major depressive disorder (MDD) who are not responding to conventional therapy, though large-scale trials are lacking [82, 83].
In a study involving 73 MDD individuals unresponsive to drug therapy, an add-on of 800 mg SAMe twice a day to antidepressant medication improved symptoms of depression compared to the placebo .
In a study of 144 individuals with MDD, 1,600 – 3,200 mg of SAM-e daily for 12 weeks significantly improved mood .
A review of 132 studies (115 clinical and 17 preclinical) concluded that SAM-e might be useful for depression. The findings were promising but data limited. The authors suggested that SAM-e may also improve symptoms of substance abuse and psychosis based on preliminary data. However, more clinical research needs to be conducted .
16) B Vitamins
A lack of B vitamins may be associated with the onset of mental health disorders, according to some theories. The body needs Vitamin B6 to make neurotransmitters like serotonin from 5-HTP (Vitamin B acts as enzyme cofactor) .
Additionally, in a cohort study of 549 community-dwelling seniors, those with low vitamin B12 and B9 blood levels were more likely to have irreversible problems with cognition (memory, attention, and thought) .
In Rhesus monkeys, a single dose of vitamin B6 increased serotonin production in the brain .
In addition, treatment of healthy adult rats with a vitamin B mixture raised serotonin levels in the brain .
More clinical data are needed.
In a meta-analysis of 17 observational studies, blood zinc levels were lower in depressed individuals compared to non-depressed individuals .
In a study, 25 mg of elemental zinc supplements daily for 12 weeks reduced depressive symptoms in a study of 37 patients with major depressive disorder .
Zinc can be increased through diet in foods such as red meat, oysters, and whole grains .
Researchers hypothesize that magnesium supplements might increase serotonin levels by increasing its availability (reducing reuptake) in the brain. In a study, 500 mg of magnesium per day for 8 weeks significantly improved symptoms in 60 patients diagnosed with mild to moderate depression .
Magnesium is found in green leafy vegetables, nuts, and legumes .
Other Supplements (Weak Evidence):
No valid clinical evidence supports the use of the supplements listed below for serotonin- and mood-related problems. We provided a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, these studies should not be interpreted as supportive of any significant mood-related effect.
20) Vitamin C
21) Vitamin E
Curcumin is the active component of turmeric. In stressed rats, curcumin extended the length of time serotonin stays active in the brain (by blocking the reuptake of serotonin). It also improved cognition and reduced serum corticosterone, a cortisol equivalent, in rats .
In mice, a single dose of curcumin (10 – 80 mg/kg) increased serotonin levels .
23) Velvet Bean
Mucuna pruriens, known as the velvet bean, may improve some symptoms of Parkinson’s disease according to limited data. In addition to being a source of dopamine, the long-term use of the powder form of Mucuna pruriens restored serotonin levels in rat brains. The effects of mucuna on mood in humans, however, is unknown .
L-theanine, an amino acid found in tea leaves (e.g. green, black, or oolong tea) and Bay Bolete mushrooms, has relaxing effects on the mind. Green tea has the highest concentration of L-theanine [105, 106, 107].
In a cohort study of over 42K Japanese individuals, those who consumed at least 5 cups of green tea a day experiences less psychological distress that is often associated with reduced serotonin .
In rat studies, L-theanine raised serotonin levels in the brain .
Rhodiola rosea is a flowering plant that may help improve anxiety and depression, though the evidence is insufficient. In a clinical trial of 89 patients with mild to moderate depression and low serotonin, Rhodiola rosea extracts (340 mg/day and 680 mg/day) for 42 days improved overall depression symptoms, including insomnia and emotional instability .
A meta-analysis of five trials of 177 participants concluded that 30 mg per day of saffron capsules may improve symptoms of depression in adults with major depressive disorder within 6 to 8 weeks. These studies were low-quality and had several limitations. More research is needed .
27) Magnolia Tree
20 and 40 mg/kg of honokiol and magnolol, the main components of Magnolia officinalis, restored low levels of serotonin in rats with chronic mild stress .
Magnolia bark and ginger rhizome are commonly used for mental disorders in traditional Chinese medicine (TCM). 30 mg/kg of a magnolia bark and ginger rhizome mixture increased serotonin in the brains of depressed mice .
28) Essential Oils
People often use essential oils as a complementary approach to anxiety, stress, low mood, and other mental health issues. Scientists posit that smelling the essential oils (inhalation) may activate pathways in the brain to boost serotonin and dopamine production, though proper clinical data are lacking .
In a study of aromatherapy in 60 elderly patients with depression, 5 ml of essential oil mixture (containing lavender, sweet orange, bergamot, and almond oil) increased serotonin levels after application two times a week for 8 weeks .
Bitter orange is an essential oil that reduced anxiety and improved mood by boosting serotonin activity in mice after 14 days of use .
Valerian is being researched for irritable bowel syndrome. In a rat study, components of the Valeriani root balanced overactive serotonin in the gut (colon) and serum .
Valeriana officinalis root extract prevented the breakdown of serotonin in mice exposed to stress .
Apigenin was able to reduce the impact of chronic mild stress in rats by increasing serotonin availability and reducing its breakdown .
Berberine is a salt derived from plants in the Berberis family (the roots, rhizomes, stems, and barks), including barberry, tree turmeric, Oregon-grape, and others. Some scientists suggest it blocks the enzyme MAO-A, which breaks down serotonin, thereby potentially raising serotonin levels .
A single berberine dose increased levels of serotonin by 47% in the brains of depressed mice. Long-term treatment with berberine (5 mg/kg for 15 days) increased serotonin by 19% .
Mice given berberine in a different study had increased serotonin levels in regions of the brain (hippocampus and frontal cortex) important for memory and mood .
Researchers found that carnitine may increase serotonin in the cerebral cortex, a region of the brain involved in cognition and memory .
Acetyl-L-carnitine (ALCAR) is a modified form of carnitine, a common dietary supplement sold in health food stores. ALCAR is marketed for protecting the brain and improving mood, though human data are lacking to support its use. In mice, it increased levels of serotonin in the brain when given daily for 25 days .
Prescription lithium has long been used in the treatment of mental disorders such as bipolar disorder. It works by increasing serotonin activity in the brain. Insufficient evidence backs up the mood-enhancing effects of (low-dose) supplemental lithium, though many people take lithium orotate to balance mood .
Physical Treatments & Devices
In one study, 24 adults with low back pain were either given two 30 minute massages per week or subjected to standard relaxation procedures over the span of 5 weeks. Urine serotonin levels were higher in individuals who received massage therapy .
Neurofeedback allows individuals to consciously change their brain activity (EEG waves) and therefore modify their behavior and cognition. Some of its proposed clinical uses are for migraines, ADHD, and PTSD [136, 137].
In one study, neurofeedback (30 minutes, 5 sessions weekly, 4 weeks) was applied to 40 patients with fibromyalgia syndrome (FMS). FMS patients may have lower serotonin and widespread pain in their muscles and bones. After 2 weeks, patients experienced less pain, fatigue, anxiety, and depression. However, this study was small and extremely short-lasting [136, 138].
In rats, acupuncture-like stimulation increased serotonin activity in certain regions of the brain .
37) Light Therapy
When sun exposure is not possible, limited research suggests that bright light therapy may help increase serotonin levels .
In a study of 25 drug-free hospitalized veterans with depression or bipolar disorder, bright white light improved depressive symptoms. However, further testing needs to be done on the negative consequences of long-term light treatment .
38) Vagus Nerve Stimulation
There is not much research about vagus nerve stimulation, mood and/or serotonin levels. The existing data are limited to findings in animals.
In rats, sustained vagus nerve stimulation for 14 days also increased the action of serotonin .
Additional Experimental Research
This section summarizes experimental research about the effects of psychedelics and MDMA on mood and serotonin in the brain. Our aim is to discuss research findings. We strictly advise against taking these substances under any circumstance.
Both psychedelics like LSD and psilocybin as well as MDMA (“ecstasy”) are illegal drugs. They are classified as Schedule I drugs, which means that they have no medical uses and a high potential for abuse and harm. Having possession of these substances can result in criminal prosecution.
The FDA recently approved a trial with a psilocybin-based drug in people with depression under a Breakthrough Therapy Designation. Another trial was approved under the same procedure for MDMA in people with PTSD. However, until the results of these studies are published and carefully reviewed by regulatory bodies, both compounds remain classified as illegal drugs.
Psychedelics are hallucinogenic drugs such as lysergic acid diethylamide (LSD) and psilocybin from Psilocybe mushrooms. Psychedelics stimulate serotonin pathways (by directly binding to serotonergic receptors and also increasing their number), raise serotonin levels, and reduce its breakdown. This likely causes hallucinations and other effects .
In a recent pilot study of 12 patients with anxiety due to life-threatening diseases, 200 μg of LSD significantly reduced self-reported anxiety. LSD was given in a safe psychotherapeutic environment with medical supervision to minimize side effects .
In a study of 17 healthy individuals, psilocybin (215 micrograms/kg) enhanced mood, increased goal-directed behavior and decreased recognition of negative facial expressions .
Using psychedelics outside a controlled and medically-supervised research environment can have serious psychological consequences. Certain plant hallucinogens, as well as synthetic hallucinogens, can be extremely toxic [149, 150, 151, 152].
MDMA, otherwise known as “ecstasy,” stimulates the release of serotonin and increases serotonin activity (inhibits its reuptake). MDMA intoxication can be severe and life-threatening, in part due to excessively increased serotonin levels .
In mice, MDMA increased both serotonin and dopamine release in the brain .
Serotonin that gets released into the blood gets rapidly broken down in the liver and lungs, to inactive metabolites (such as 5-HIAA) that are excreted in urine .
That is why, normally, blood and urine contain very small amounts of serotonin. Larger quantities of serotonin in the blood/urine can be found in people with serotonin-producing tumors (carcinoid tumors).
Beware of the use of urine serotonin levels to check for “neurotransmitter imbalances.” While the companies providing these tests state that the levels in urine correspond to brain neurotransmitter levels, science has repeatedly shown that this is not the case .
Serotonin doesn’t cross the blood-brain barrier. Even if it did, it is released intermittently and influenced by many different stimuli. Furthermore, levels differ within different parts of the brain. And finally, values differ for the same person from one day to another .
In addition, companies have been known to intentionally use extremely narrow ranges, without any scientific support whatsoever, in order to sell supplements to their clients !
A PET scan is the only direct way to detect changes of serotonin production in specific areas of the brain .
Risks and Safety
MDMA, LSD, and other synthetic drugs may cause serotonin syndrome, and should not be taken without medical supervision or outside a psychotherapeutic environment .
Most of the studies mentioned above were performed on adults. More research involving children is needed in order to determine safety. The long-term safety of most approaches listed here is unknown.
Abnormally heightened levels of serotonin (hyperserotonemia) is a consistent finding in individuals with autism. Pregnant women with hyperserotonemia are more likely to give birth to children with autism [162, 163].
The use of St. John’s Wort, SAMe, or lithium simultaneously with serotonergic drugs like selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAO-I), and triptans, can increase the risk of serotonin syndrome, a life-threatening and potentially fatal condition [164, 165, 166].
Limitations and Caveats
Some of these studies have fairly small sample sizes. Additionally, many of these natural methods of increasing serotonin in the body have only been tested in animals. Further research in humans is necessary to determine their safety and effectiveness.
In addition to the concentration of serotonin, both the number of serotonin receptors and their sensitivity may also play an integral role in determining serotonin activity.
Though serotonin is mostly made, stored, and released in the gut, serotonin acts as an important neurotransmitter in the brain. Some of these natural remedies and supplements need further testing to determine if they are able to cross the blood-brain barrier. Long-term application of these remedies should also be further studied.