The Ultimate Guide to Serotonin: The Mood Neurotransmitter

Let’s begin with the nitty gritty of neurotransmitters. Your brain communicates with itself and other parts of your body through chemical messengers called neurotransmitters. You have an intricate system of nerve cells, called neurons. Neurons are specialized cells that transmit impulses and send messages throughout your body, communicating to one another. 

When a nerve releases a neurotransmitter “message” it crosses a small gap called the synapse, then attaches to a receptor on the next nerve. Think of these like internet connections. 

But instead of being connected by a wire, they have a small gap called a synapse between one another. Almost like wifi versus dial up. 

This gap allows for the electrical impulse to be changed into a chemical signal, in order to send the right message. 

Neurotransmitters are chemicals that send messages through this gap, between neurons or from neurons to muscles. 

Neurotransmitters bind at the receiving cells (receptors) and trigger changes. Just like a key and lock, the neurotransmitters can “open the door” to a new action. If the key matches the lock, the message is received, if not, it either waits to get reabsorbed or enters at a slower pace. 

These key-like chemicals impact endless functions of the nervous system and your body. When they work in harmony, you feel good, have a sharp mind, and a well behaved body. Physical and emotional equilibrium. 

But when the brain and body communication systems break down, your psychological well-being may suffer. Too much or too little neurotransmitter levels are associated with disorders such as depression, anxiety, or physical ailments. 

Neurotransmitter Support Team

We all need a helping hand. A neurotransmitter starts as a precursor. To support precursors in becoming a neurotransmitter and balancing your brain, they require helper molecules, known as cofactors.

Precursors

Simply put, a precursor is a substance from which another is formed. It’s an inactive substance that becomes an active one, such as a neurotransmitter. It’s derived from an available source -- typically from your diet or supplements.

Cofactors

A cofactor is an organic molecule that is required for enzymatic activity, or revving up a reaction in your body. They’re considered to be helper molecules that assist in transformation. A cofactor starts the engine on a process of change.

Notable Neurotransmitters 

Your body is constantly adjusting and adapting to what’s thrown at it; rebalancing and creating homeostasis. The key is to support your body in manufacturing a healthy amount of neurotransmitters. With neurotransmitter unanimity, you get:

Enhanced mood and regulated emotionsMore motivation to do the things you loveAcute focus; think clearly and being present in your favorite activities Restful and rejuvenating sleep Movement, attention, learning, motivation, behavior

This chapter will teach you what serotonin really is and why it’s so crucial to well-being. 

Serotonin is a neurotransmitter found throughout the central nervous system and digestive system. Serotonin is often called the “happy molecule” because it:

*Supports a positive mood

*Maintains a healthy appetite and digestion 

*Promotes calmness and a sense of well-being

*Relieves stress and frustration 

Serotonin is most commonly believed to be a neurotransmitter but also considered to be a hormone. It’s produced in the brain -- influencing mood, stress, and happiness; and the gut -- enhancing the absorption of nutrients, stimulating  contractions of the intestines, and facilitating the passage of food. 

Small amounts of serotonin are produced in the brain while over 90% is made in the gut [1]. 

Only serotonin produced in the brain can be used by the brain. 

Serotonin doesn’t cross the blood-brain barrier, so any that is used by your brain has to made in your brain. 

Definition
Serotonin is a neurotransmitter; one form of “communication” in your body and brain. It’s linked to mood, happiness, and a positive outlook. Serotonin is considered to be a natural mood balancer, helping support stress and boost mood. 

Serotonin is created by a chemical conversation process that combines tryptophan (an essential amino acid) with tryptophan hydroxylase (an enzyme) to form 5-hydroxytryptamine (5-HT), also known as serotonin [2]. 

Serotonin aids with eating, digesting and sleeping. 

Function
Serotonin’s impact extends outside the brain. It plays a key role in the body including the gastrointestinal tract, bone formation and breakdown, and reproductive health effects.

Gastrointestinal Tract
Serotonin is mainly produced and found in the body’s stomach and intestines, which means that it has a direct relationship to bowel function and many intestinal disorders.

The gastrointestinal system is often called a “second brain” because the enteric nervous system (found in the gastrointestinal tract) communicates back and forth to your brain. Irritation of the gastrointestinal system may trigger signals to the brain which can trigger mood changes. 

This may explain why more people suffering from irritable bowel syndrome (IBS) and bowel problems (constipation, diarrhea, bloating, pain, stomach upset develop depression, anxiety, or emotional shifts [3].

“Reports of plasma 5-HT concentrations in different functional GI disorders suggest that there may be a role for circulating serotonin in determining predominant bowel function: serotonin is increased in diarrhea and celiac disease, decreased in constipation.” [4] 

Serotonin is one of the reasons you become nauseated. This is because its increased in order to expel food or bacteria that could cause illness. It helps get things out quick!

Mood
In the brain, serotonin regulates stress, happiness, and mood. Low levels have been associated with depression while increased levels, to the point of excess, are thought to decrease arousal.

In healthy human subjects, increases in serotonin system messaging results in enhanced attention and recognition of positive emotional thoughts and feelings. In general, decreased serotonin results in less attention and recognition of positive emotional material and increases the attention bias towards negative thinking [5]. 

A change in the serotonin transporter gene also alters emotional processing. Meaning that when it comes to medications, it’s important to focus on and target various serotonin receptors for the treatment of cognitive and affective disorders [5]. 

Sleep
Serotonin is responsible for stimulating the parts of the brain that control sleep and waking, including helping with the production of melatonin. Serotonin is a precursor to melatonin, the hormone that helps you fall asleep. It also regulates sleep-wake cycles. Different serotonin receptors are used depending on whether you’re awake or asleep.

Blood Clotting
Serotonin is involved in blood clotting because blood platelets (blood cells that help your body form clots to stop bleeding) release serotonin to help heal wounds. Serotonin also makes your arteries become more narrow, helping with the clotting process. 

Bone Strength
Serotonin can impact bone health and structure. High levels of serotonin in the bones can lead to osteoporosis (a condition where the bones become brittle and fragile). Serotonin is one of the local factors in physiological bone remodelling. It is thought that the bone can be viewed as a micro-serotonergic system [6]. 

Reproductive Health
In general, low levels of serotonin are associated with increased libido while increased serotonin is associated with reduced libido [7]. This means that some antidepressants which increase serotonin may cause sexual problems. Stopping the synthesis of serotonin (resulting in a serotonin decrease) can also increase sexual behavior [8]. Serotonin also helps form breast milk.  

Serotonin Agonists
A serotonin receptor agonist is a compound that activates serotonin receptors. They kick start signaling pathways that lead to changes in gene expression. They activate serotonin receptors in a manner similar to serotonin. 

Serotonin agonists mimic serotonin by binding to proteins on the neurons called serotonin receptors. There are several types of serotonin receptors and particular types are more involved in movement. In the medications, the agonists are man made and designed to bind to and activate particular serotonin receptors on neurons. 

Serotonin receptors
A neurotransmitter receptor, also known as a neuroreceptor, is a protein that receives neurotransmitter messaging. They are activated and receive messages according to the type and amount of neurotransmitter present in the synapse. 

In order to understand how they work, it’s first helpful to understand the difference between excitatory and inhibitory functions:

Excitatory: Promotes an electrical signal or impulse that is then allowed along the muscle or nerve cell.
Inhibitory: The receiving neuron prevents an electrical signal from being received. 
Modulatory: Not just restricted to the synaptic cleft (the area between two neurons) so they can impact many neurons at once. This happens over a slower time than excitatory and inhibitory transmitters. 

There are three serotonin receptor families: 5-HT1, 5-HT2, and the family that include 5-HT4, 5-HT6, and 5-HT7. Each serotonin receptor can be activated by serotonin but differences in signal mechanisms create opportunities for drug targets [9]. 

To give you an idea of differences in receptors, one example is serotonin impacting psychedelics such as psilocybin, DMT, LSD, and MDA. These are non-selective agonists of serotonin receptors with the hallucinogenic effects coming from activation of a specific receptor. 

Serotonin receptor targeting medications include antidepressants, antiobsessional, and appetite suppressants.

Until recently, it was thought that neurotransmitters were generally separate. For instance it a neuron is inhibitory, it releases GABA, and if it’s modulatory, it releases another neurotransmitter such as dopamine. But new studies show that certain neurons can release more than one neurotransmitter [10]. 

Each neurotransmitter system does not operate in isolation, rather your body is constantly balancing the neurotransmitter chemistry. 

Dopamine
Dopamine and serotonin are both naturally occurring chemicals that influence mood, happiness, motivation, and well-being. Serotonin is known as the “happy” neurotransmitter where as dopamine is known as the “motivation” or “reward” neurotransmitter. Dopamine dysfunction tends to be linked to certain symptoms of depression, such as low motivation. Serotonin is more so involved in processing emotions, which can affect your overall mood.

Take the quiz: Are you dopamine or serotonin dominant?

GABA
Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that has a relaxing and calming effect on the brain. Serotonin is also inhibitory.

While dopamine and acetyl-choline are associated with energetic, motivating action; GABA and serotonin are more of the mellow neurotransmitters, maintaining balance and rhythm in your body and mind. 

Acetylcholine
Acetylcholine is a neurotransmitter essential for brain processing. It helps increase mental clarity, improve thinking, and cuts through brain fog. 

Previous research has shown that acetylcholine interacts with serotonin at the hippocampal level (part of the limbic system which helps regulates emotions) which may have consequences for cognitive functioning. However, little is known about the exact nature of this interaction as well as possible effects on brain processing [11].

Science and new research is always changing. Take a look at what’s changed in relation to serotonin over the years!

The prevailing theory used to be that low serotonin was what caused negative emotional states of mind. Older studies found that people with depression tend to have low levels of serotonin [12]. However, recent research has flipped this hypothesis. 

It is not clear what exactly causes depression but scientists also think that depression is caused by an imbalance in neurotransmitters or hormones [13]. There’s a debate about whether low levels of serotonin cause depression, or if depression causes serotonin levels to drop.

But one thing is known: 

Between 80 and 90% of people who have depression, benefit from treatment -- varying from medication to therapy to lifestyle change [14].

Low levels of serotonin can also lead to mental health problems including mood disorders, anxiety, depression, OCD, PTSD, phobias, and epilepsy. [5] Animal studies have supported the theory that low serotonin levels can make you more susceptible to social stressors. [7] In a 2016 animal study, mice with higher than normal levels of serotonin in their brains were found to display fewer behaviors associated with anxiety and depression. [8]

Medication and Drugs
Antidepressant medication can change brain chemistry. When a neurotransmitter message is sent, the neurotransmitters have to be taken back and replaced in a process called reuptake. Certain medications can block this reuptake process, keeping serotonin built up in between neurons so the message can be sent correctly. 

Common antidepressants such as Prozac work by boosting the serotonin levels in your brain. Same happens with illegal drugs such as ecstasy and LSD -- there’s an increase in serotonin levels leading to a high [4].

Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are commonly prescribed antidepressants. They work be enhancing the function of nerve cells in the brain and keeping serotonin built up in between neurons, longer. While SSRIs are thought to work well for people with major or severe depression, the benefits are unclear for people with mild or moderate depression. [13]

Some scientists argue that SSRIs may accelerate the turnover of serotonin making any deficiency worse. This is because SSRIs only inhibit the absorption of the chemical, they don’t help your brain produce more. [14]

Common SSRIs include:

*Fluoxetine (Prozac)

*Escitalopram (Lexapro) 

*Citalopram (Celexa)

*Sertraline (Zoloft) 

*Paroxetine (Paxil) 

SSRI Side Effects
Symptoms and side effects can vary greatly from person to person. The most common symptoms of taking SSRIs include: 

HeadachesRashInsomniaVision difficulties Fatigue or tirednessDry mouthAgitationDizzinessUpset stomach, nausea, or diarrheaReduced sexual drive [15] 

It’s always important to work with your physician, express any concerns, and find out which (if any) medication is right for you.

Serotonin and Stress
Recent studies have reported that elevated cortisol (the “stress hormone”) levels caused by stressful life events, may lower brain serotonin function and lead to the manifestation of a depressive state [16]. In fact, about 50% of patients with major depression output large amounts of cortisol. Cortisol is not necessarily a characteristic feature of depression, however there are some relations. 

Whether your stress is caused by a life-threatening physical attack (acute stress), or a nerve-wracking period of job instability (chronic stress), your body will respond in the same way. It will trigger the fight or flight response by releasing the stress-hormones cortisol and epinephrine, and inhibit neurotransmitters such as serotonin and dopamine that keep you calm. [17]

This reaction is helpful for acute stressful situations, but too much stress over time, also called chronic stress, can lead to health problems such as insomnia, weight gain, digestive problems, heart disease, and serotonin deficiency. [18]

Other causes of serotonin deficiency include: poor diet, genetics, digestive issues, exposure to toxins, hormone changes, lack of sunlight, alcohol, caffeine, nicotine, drugs, and prescription meds.

The prevailing theory stated that low serotonin is what caused negative emotional states of mind, but now leading researchers believe serotonin imbalance is a more likely predictor of these negative emotional states [19].

Serotonin can’t pass through the blood-brain barrier so urine or blood tests can’t determine the level of the chemical in your brain [20]. This makes serotonin deficiency difficult to diagnose and the link between serotonin and emotions hard to identify. However, common symptoms of high and low levels of serotonin do exist. 

Serotonin Deficiency Symptoms
The most widely recognized symptoms of low serotonin are sadness and loss of pleasure [21]. Low levels of serotonin have also been linked to insomnia as the chemical is a precursor to melatonin, the hormone that signals to your brain it’s time to sleep.  

According to Integrative Psychiatry, the conditions related to serotonin deficiency are varied and can include:

*Depression
*Anxiety
*Panic Attacks
*Insomnia
*Irritable bowel disease (IBD)
*Premenstrual syndrome (PMS)
*Fibromyalgia
*Obesity
*Eating disorders
*Muscle pain
*Chronic pain
*Alcohol abuse [22]

Other signs and symptoms of low serotonin include:

*Mental obsessions
*Compulsiveness
*Depressed mood
*Sleep-cycle disturbances
*Sweet and starchy food cravings
*Increased appetite
*Low libido
*Irritability
*Digestive health issues
*Joylessness
*Sense of overwhelm

A study from 2007 showed that men and women respond differently to low serotonin levels [23]. For men, poor mood and lack of interest or ability to focus are more commonly the result of dopamine deficiency. For women, the most common signs of low serotonin are anxiety, cautiousness, and a general drop in mood.

Negative mood, anxiety, depression, impaired social behavior, aggression, fear, stress, and increased appetite are all factors that can result from the effects of a serotonin imbalance. Maintaining healthy serotonin levels is linked with improved physical and psychological symptoms, positive social behavior, and greater overall health [24].

Serotonin Deficiency Causes
Researchers don’t have a definitive answer for the exact cause of serotonin deficiency. It may partially due to the fact that everyone is different and simply produce less than others. For instance, some people may have fewer receptors. 

Lifestyle and life experiences also play a factor. Low levels of L-tryptophan, vitamin D, vitamin B6, and omega 3 are needed to make serotonin. Serotonin may be low if these are lacking from the diet. Life experiences such as abuse can also lead to less serotonin [25]. 

Factors that can cause or contribute to low serotonin levels:

*Prolonged states of stress
*Genetic predispositions
*Some drugs and prescription medications
*Lack of sunlight
*Hormonal fluctuations, deficiencies, or imbalances
*Poor diet
*Lack of exercise
*Caffeine
*Cigarette smoking
*High cortisol levels
*Problems converting tryptophan to serotonin
*Low blood sugar

There are dozens of lifestyle factors that can influence serotonin levels either positively or negatively, but in order for the body to build this neurotransmitter in the first place, we need to get adequate amounts of dietary precursors -- the fundamental building blocks of serotonin. More on this in the next chapter!

Can You Have Too Much Serotonin?
High levels of serotonin and serotonin toxicity occur when levels of serotonin exceed the normal amount in the body. 

Symptoms of high levels of serotonin include:

*Shivering
*Muscle stiffness
*Confusion
*Restlessness
*Agitation
*Rapid heart rate
*Sweating
*Loss of coordination
*Twitching muscles

In more extreme cases, high levels of serotonin can result in a condition called serotonin syndrome.

What is Serotonin Syndrome?

Serotonin syndrome is the result of overactive serotonin receptors in the brain, which leads to higher levels of serotonin [26]. It can occur when you increase the dosage of an existing medication, or possibly if you add a certain new drug to your regimen. Additionally, certain illegal drugs are associated with serotonin syndrome.

Serotonin syndrome is most often the result of medication use or complication, and while natural supplements have been shown to increase serotonin levels, when taken as recommended, the risk of excess serotonin levels is very low.

There are many pharmacological strategies to improve serotonin levels in the brain, but the research shows that there are effective ways you can improve serotonin levels naturally.

Exercise
Physical activity has been shown to significantly increase serotonin levels in both human and animal studies [27]. Exercise has been found to be as effective as the SSRI sertraline in a randomized controlled trial [28]. 

Studies have shown that exercise increases the firing rates of serotonin neurons, which results in increased release and production of serotonin [29].

Exercise also triggers the release of the serotonin precursor, tryptophan, in the brain [30], setting your brain up to make its own serotonin. Some evidence shows that exercising to feeling fatigue is associated with a further increase in serotonin [31].

Studies have shown that aerobic activities such as cycling and running are the most effective at increasing serotonin levels but there is some evidence to show this isn’t the case if you feel forced into exercising or just don’t feel like it [32].

Exercising regularly is one of the key components of a healthy lifestyle, so it’s important to find an activity you enjoy. If you don’t feel like going for a run, try practicing yoga instead. There is evidence to show that techniques learned from yoga can help you cope better with stress. [33]

Exercise increases the availability of serotonin precursors as well as the activity of serotonin receptors in the brain. 

Mindfulness Activities
Self-induced alterations in thought, such as mindfulness meditation or even positive thinking, have been shown to alter brain metabolism and influence serotonin levels [34]. 

Activities that emphasize a positive mood like gratitude journaling, meditation, gratitude, or positive psychology are practical ways to improve symptoms of serotonin imbalance and mood, possibly even independent of one another.

Studies have shown that meditation increases levels of serotonin by reducing the body’s natural stress response. Meditation may also slow your heart rate and reduce your blood pressure. [35]

If you’re suffering from chronic stress your serotonin levels are likely to fall again as soon as your body triggers a stress response. Boosting serotonin is only part of the solution. The following stress management techniques may help.

Meditating regularly may also help relieve stress and make you feel more positive. In fact, some studies suggest that positive thinking can in itself increase serotonin levels, so take some time each day to think about what you are grateful for and remember happy events. [34]

Sunlight
Your body is designed to be exposed to UV light during the day. Your body needs UV light in order to turn it into vitamin D which is essential for the production of serotonin.

One way of naturally boosting your serotonin levels is to make sure you spend some time out of doors every day. Light therapy products are available as an alternative if you live in a climate with little sunshine. To help you get a good night’s sleep - turn off your devices in the evening and ban them from the bedroom.

Exposure to bright light is a standard treatment for seasonal affective disorder (SAD), but researchers believe serotonin levels are affected as well [35]. Studies done in humans and animals reveal a positive relationship between hours of sunlight per day and serotonin synthesis [36]. Even during the winter months, simply spending more time outdoors was shown to boost serotonin levels in the brain.

Another study showed that the mood-lowering effect of tryptophan depletion in healthy women was completely blocked when exposed to bright light instead of dim light [37]. 

Relatively few generations ago, our ancestors were more deeply involved in agriculture, and spent much of the day outdoors. Now, we live in a natural bright light-deprived society, which is believed to be a contributing factor to SAD and modern society's prevalence of mood disorders.

Create a Healthy Sleep Routine
Nothing is more beneficial to your mental health that a good night’s rest. Quality sleep is essential to give your brain the chance to flush out toxins, and repair and regenerate brain cells. Missing out on sleep or getting a poor night of sleep can reduce extracellular serotonin [38]. 

If you’re wondering how to fall asleep fast and naturally, try establishing a healthy sleep routine. Switch off devices in the evening, do something calm such as listening to music or talking a warmth bath, and avoid stimulants such as caffeine and alcohol a couple of hours before bedtime.

Healthy Diet, Rich in Serotonin Precursors & Cofactors
To produce serotonin in the first place your body needs the right nutrients. Eating a varied diet rich in vitamins, minerals, and nutrients helps provide the body the necessary cofactors and precursors to support optimal serotonin metabolism and function. 

Tryptophan
That process of serotonin creation starts with tryptophan, an amino acid used at the beginning of the metabolic cycle to kickstart serotonin production [39].

The following foods are good sources of tryptophan:

*Eggs
*Cheese
*Nuts
*Turkey
*Salmon

Serotonin Supplement
Though many foods contain tryptophan, other amino acids can "compete" for absorption. Also, this chemical can’t cross the blood-brain barrier so eating them may not directly boost serotonin levels in your brain. That's why purified tryptophan sources or 5-HTP (the next precursor in the metabolic cycle) are more easily transported into the brain. 

A serotonin supplement or a mood stack that combines serotonin with other nutrients that support your body in reaching optimal levels, naturally.

Look for a supplement that contains the precursor tryptophan, plus additional cofactors like B vitamins, magnesium, and zinc. 

Balance Your Diet

In order to support your brain and body in producing healthy amounts of serotonin, include these in your diet:

*Healthy proteins including wild-caught fish, organic chicken, beans, and eggs
*Whole grains such as cereals and brown rice
*Foods high magnesium and calcium such as leafy greens, wild-caught fish, nuts
*Foods high in Vitamin B such as cereals, beans, peas, nuts, liver, dairy, and eggs
*Omega-3-rich foods such as wild-caught fish, nuts, and seeds

Boosting your diet with quality supplements such as krill oil can help you to get all the Omega-3 fatty acids that you need.

Serotonin and Sugar
Sugar appears to suppress the production of BNDF, an essential brain protein that helps to calm anxiety. Caffeine releases the stress hormone, cortisol, and triggers the body’s fight or flight response.  Drinking too much alcohol over time may alter your brain chemistry and make you less able to cope with stressors and impact serotonin production.

Serotonin and Carbs
A new study was conducted, comparing different types of carbs and their effect on metabolic blood biomarkers [40]. This study discovered that adults who consumed whole grain rye had lower plasma (blood) serotonin levels than those eating low fiber, refined wheat bread.

Only serotonin produced by the brain can be used by the brain. In the gut, serotonin’s main role is digestion and satiety. So when you have too much serotonin in the gut or blood stream, it may cause digestive issues or other problems. In fact, increased blood serotonin has been associated with high blood sugar.

It’s best to focus on whole grains which still have the bran and germ intact. These are layers of the grain that contain healthy nutrients such as fiber, selenium, potassium, and magnesium.

Whole grains include: 

Barley
Brown rice
Buckwheat
Whole wheat (bread, pasta, crackers)
Oatmeal

Understanding Serotonin Imbalance: The Bottom Line

Nobody knows exactly what causes “the blues” or negative emotional states.

Brain chemistry is an incredibly complex field; it's one that’s continuing to change every year.

However, serotonin does play a key role in your ability to feel calm, relaxed, and happy.

The most powerful way to heal your bodies and minds is through regular movement, healthy diet, making a deliberate effort to de-stress, and soaking up plenty of sunshine on a daily basis.

These are our most powerful tools for living a happy, healthy, and balanced life.

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