Neurotransmitter Issues

Why is it that even if we know something is bad for us, we have a difficult time removing it from our lives? Friends supposedly close enough to us to be able to be truly honest say “You need to try harder!” or “It just takes willpower!” or something else that leaves us feeling less than good about ourselves.

One day I found myself eating another piece of chocolate I knew I didn’t need and wondered what was driving my desire to do so. Mind you, I am pretty well versed in blood sugar issues and food addictions, yet that chocolate went directly from my hand into my mouth without a moment’s hesitation.

It was a gradual process. I hadn’t eaten chocolate for 6 months, so I had just a little bite for fun. No big deal. The next day, another bite. Within a week, the bar was gone and I went out to get more. After that, the amount of chocolate I ate and frequency at which I ate it kept increasing. Suddenly I had “lost my willpower,” but why? That struck me as strange. Me being me, I had to understand what was going on from a biochemical perspective. Let’s look at what I found.

Note: if chocolate doesn’t resonate with you, try substituting alcohol, sugar, negative emotions, rituals, etc. for chocolate.

Change can be a chemical issue

I want to point out that if you are one of those folks who feels that change has been too hard in the past, please keep in mind that motivation is not necessarily all just in our heads.

Anything that affects our neurotransmitter levels (or brain health like neuroinflammation) may also affect our motivation, so quit beating yourself up! As you heal, your ability to follow through on all of the things you want to accomplish in life will also improve.

So let’s get started.

What are neurotransmitters?

We believe that we are in control, but it turns out that our brains and emotions are governed by chemicals called neurotransmitters. These neurotransmitters are responsible for keeping us alert, motivated, smart, and just plain happy. When they are well-balanced, we are productive, birds sing, flowers bloom, and all is good with the world.

But if our neurotransmitters go awry? Then we are welcoming Dr. Doom and the associated depression, anxiety, apathy, anger, poor memory issues, or any of a myriad of negative fallouts that go along with poorly balanced neurotransmitters.

No doubt that you have heard about endorphins, our internal “feel-good” chemicals. In addition to endorphins, we make use of other chemicals such as serotonin, dopamine, GABA, glutamate, and acetylcholine to send messages between the cells in our brain.

How do neurotransmitters aid in communication?

Imagine, if you will, our brain cells as a two-legged starfish. Each leg has a dedicated job. One “leg” (or axion) sends messages, and the other “leg” (or dendrite) receives them. What if there is a predator nearby? How does the starfish warn its family and friends of the danger?

Like this starfish, each brain cell or neuron is isolated by a physical gap or synapse between them. If one cell needs to pass along a message to the next cell, it must somehow cross this space. To illustrate how this works, say you put your hand on a hot stove. The pain message needs to travel from the cell to all the way to the brain to register that the stove is hot! 

To cross the gap/synapse, we need a messenger to pass along the information quickly (this particular reflex pathway doesn’t exactly work this way, but let’s go with it). This messenger is called a neurotransmitter. It is a chemical messenger, and when enough of it is sent, it activates the next cell’s dendrite to receive the message.

At that point, its job is done, and the neurotransmitter disappears. Think about what would happen if it didn’t disappear—what if there was a hardwired connection between each cell? How could we be sure that the message was deleted so that we didn’t keep feeling the same pain over and over?

How are neurotransmitters made?

Most neurotransmitter production begins with amino acids from the diet or from chemicals found in the brain which are converted by enzymes, methylation, and nutrients cofactors such as B vitamins, minerals, vitamin D and others.

What are some neurotransmitter “rules”?

Other key things to keep in mind:

  1. Neurotransmitters can either stimulate or inhibit activities in the body.
  2. Although there is only one sender and one neurotransmitter associated with any given message, the number of receptors and their sensitivity to the message can be altered based on how often the same type of message is sent.
  3. We require amino acids, vitamins, minerals, and enzymes to make our neurotransmitters


Understanding this can help us understand what can go wrong.

So what can go wrong with neurotransmitters?

Neurotransmitters dysfunction may form the basis for emotional issues and unwanted behavior. How are we expected to make lifestyle changes if our own neurotransmitters turn on us?

Even if we have the right environment with plenty of enzymes, ample cofactors, and raw materials to make them, they may not function as intended. Why?


We require enzymes to manufacture and clear our neurotransmitters. If there are any genetic weaknesses or SNPs, the body may have an issue making and/or clearing them. This often occurs with people who have specific genetic defects with neurotransmitter clearance such as slowed MAO, COMT, GAD or NOS enzymes.

Receptor Issues

If the cells cannot effectively clear the neurotransmitter from the synapse after the message has been received, even normal amounts of it could cause the receptors to become less sensitive to the neurotransmitter.

Let’s consider this scenario: say pizza was the only food on the planet. You eat pizza every day of every week of every month. How soon would you get tired of the taste of pizza? It probably wouldn’t take long.

Our cells feel the same way. If presented with too much of something over and over, they shut down just as we would refuse to accept any more. That means that if our receptors see too much of any hormone or neurotransmitter over time, they reduce the number of receptor/binding sites, effectively ignoring whatever message your body is trying to send. This is called downregulation. At that point, more and more of the hormone is required to initiate a response.

This may be the reason why that for many folks, selective serotonin reuptake inhibitors (SSRIs) seem to help at the beginning of their treatment but then tend to lose their effectiveness over time—eventually, the body simply tunes them out.

Gut Issues

Proper gut function is absolutely necessary to provide the requires enzymes, cofactors, substrates, etc. that support the production, usage, and removal of neurotransmitters. 

Vagus Nerve

Vagus nervee integrity is extremely important since it ties our two “brain”, the gut and brain together. If you have ever had “butterflies” in your stomach when feeling stressed or scared, you had first-hand experience with this connection.

But keep in mind, this connection goes both ways. For instance, over 1/2 of folks with gut issues such as Irritable Bowel Syndrome (IBS) also have symptoms of depression. According to Dr. Alex Vasquez DC, ND, DO, “90% of the vagal fibres between the gut and brain are afferent, suggesting that the brain is more of a receiver than a transmitter with respect to brain-gut communication.”

Communication between our gut and brain is via hormones, immune messengers, and neurons. That being said, there are many different mechanisms that may be associated with mood. 


It goes without saying, diet is important. Without the correct nutrients, we cannot manufacture or utilize our neurotransmitters. For instance, studies have shown that cultures with traditional healthy dietary patterns have a 25 to 30% lower rate of depression.

As mentioned, we need nutrient cofactors and amino acids to make our neurotransmitters. Julia Ross, author of Mood Cure, lists indicates conditions that may be affected by the lack of specific amino acids.

  • Anxious or stressed? Low GABA, may need GABA
  • Depressed or anxious? Low serotonin, may need Tryptophan or 5-HTP
  • Tired or unfocused? Low stress hormones, may need Tyrosine
  • Wanting a reward or sad? Low endorphins, may need DPA (d-phenylalanine) or tyrosine

There is a bit of controversy on whether the amino acid GABA referred to above crosses the blood-brain barrier since it is such as large molecule. Dr. Kharrazian, DC, states that if you respond to GABA, you may have a permeable brain barrier which needs to be addressed.

Blood sugar regulation

Blood sugar control matters. Studies point to an elevated risk of depression in those with insulin resistance. So, it is not only what you eat, but how you eat, that may affect neurotransmitter function.


Important as above issues are, they may not be the fundamental cause. The Human Microbiome Project, launched in 2008, is creating a paradigm shift in world of neuroscience. Infections and inflammation alter the species and population density of our resident microbiota. This means that our unique biome influences our brain activity and neurotransmitters influence.


Inflammation may affect the integrity of our intestinal barrier allowing allergens and toxins to directly enter into the bloodstream. This inflammation can also alter the blood brain barrier where toxins such as Lipopolysaccharide endotoxins (LPS) can cause microglial cell activation in the brain. This can then affect neurotransmitters and brain function.

Another thought. Growing evidence shows that the brain’s dopamine system, which drives motivation, is directly affected by chronic, low-grade inflammation. Trends in Cognitive Sciences 2019 paper proposes that this connection between dopamine, effort, and the inflammatory response is an adaptive mechanism to help the body conserve energy.

“When your body is fighting an infection or healing a wound, your brain needs a mechanism to recalibrate your motivation to do other things so you don’t use up too much of your energy,” says Michael Treadway, an associate professor in Emory’s Department of Psychology. “We now have strong evidence suggesting that the immune system disrupts the dopamine system to help the brain perform this recalibration.”

Oxidative stress

Finally, an overload our antioxidant system can influence neurotransmitter status. Issues caused by inflammation, hypoxia (low oxygen), infection, etc. may compromise our ability to methylate which can in turn, minimize neurotransmitter production.

What are some symptoms of neurotransmitters issues?

  • Serotonin – Sleep disruption, depression, anxiety, PMS, temperature dysregulation, pain issues, appetite issues, inability to make change
  • Dopamine – Issues with focus, attention, memory, motivation, drive, mood, addictive disorders, voluntary movement
  • Norepinephrine – Issues with energy, drive, stimulation, “fight or flight” response, insomnia, anxiety
  • Epinephrine –Issues related to  “Fight or Flight response”, metabolism, energy, depression, cognitive function
  • GABA – anxiety, excess stimulation with light, sound, touch, etc.
  • Glutamate – Issues with learning, memory, agitation, sleeplessness, depression when low

Can I support my neurotransmitters?

Diet and regular exercise can go a long way. Stress relief by being around those you make you feel good and doing the things that you love. Finding root cause as described above.

Temporary supplement support can help and depends on the neurotransmitter and how it is affected. Please work with your provider.

Can I test my neurotransmitters?

Although thee are Functional Medicine tests that look at urinary neurotransmitter issues, these are the output at the periphery and may not correlate to levels at the brain. Organic acids testing does look at some intermediates from other cycles that interact with neurotransmitters such as glutamate which may provide an indirect measure. 

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