The Chemistry of Anxiety and Depression

March 02, 2021

Balancing Neurotransmitter Activity to Overcome Anxiety, Depression, Insomnia, and Inflammation

Neurotransmitters are chemical messengers that communicate information throughout the brain and body. These chemical messengers tell your heart to beat, your lungs to breathe, and your stomach to digest.  They can also affect mood, sleep, concentration, and weight, and can cause adverse symptoms when they are out of balance. Neurotransmitter levels can be depleted, or imbalanced, in many ways.  An estimated 86% of Americans have suboptimal neurotransmitter levels.  Stress, poor diet, neurotoxins, genetic predisposition, drugs (prescription and recreational), alcohol, and caffeine usage can cause these levels to be out of optimal range. The key to managing issues like anxiety, depression, insomnia, chronic inflammation (and more) is a proper balance between excitatory and inhibitory neurotransmitters. While excitatory neurotransmitters stimulate the brain, inhibitory neurotransmitters balance mood and are easily depleted when the excitatory neurotransmitters are overactive.

neurotransmitters 101

Excitatory Neurotransmitters

Excitatory neurotransmitters facilitate the firing of nerves. They can be thought of as your body’s gas pedal, or accelerator – they get you going!

going fast downhill


Glutamate is the primary excitatory neurotransmitter in our Central Nervous System. In the right amount, it is crucial for higher cognitive function like learning and long term memory. Too much glutamate in your system goes hand in hand with high anxiety levels.


Norepinephrine is another important excitatory neurotransmitter to note.  Stress signals the release of norepinephrine in order to increase alertness, heart rate and arousal, speed up reaction time and dump glucose into your bloodstream.

The release of norepinephrine triggers the activation of Parasympathetic Nervous System, aka your ‘Fight or Flight’ response. Norepinephrine plays a major role in mood, ability to concentrate and anxiety levels. Severe anxiety is marked by a surge of norepinephrine in the brain. Low levels of norepinephrine are associated with low energy, difficulty focusing and poor sleep.


Dopamine, the brain’s “pleasure and reward center” is the primary actor when it comes to focus and motivation. When dopamine is either elevated or low you can experience issues focusing, forgetting where you put your keys, find yourself daydreaming a bit too much, etc.¬† Dopamine is also responsible for our drive or desire to get things done.¬† Stimulants, like ADD/ADHD medications and caffeine, cause dopamine to be pushed into the synapse in order to improve focus. Unfortunately, stimulating dopamine consistently can cause a depletion of dopamine over time.

Inhibitory Neurotransmitters

Inhibitory neurotransmitters inhibit [stop] the firing of other nerves. If excitatory neurotransmitters are your body’s accelerator, then inhibitory neurotransmitters are the brake pedal.

mountain landscape with sign that says slow now


GABA is our bodies’ primary inhibitory neurotransmitters. It decreases nervous system activity by stopping the firing of certain brain signals and slowing the activity of excitatory messengers like glutamate. GABA isn’t just glutamate’s counterpart, it’s actually its byproduct as well. Ideally, with healthy neurotransmitter activity and normal stress levels, glutamate gets converted to GABA and the two balance each other out nicely. With chronically elevated stress levels signaling an excess of glutamate in your system, the conversion to GABA maxes out at a certain point and you’re left with an imbalance: too much gas, not enough brake.

Healthy GABA activity is a key factor in getting a good night’s sleep, managing anxiety, and generally switching off the ‘Fight or Flight’ stress response and switching on the ‘Rest and Digest’ system.


Serotonin is another inhibitory neurotransmitter that plays a critical role in mood, anxiety, sleep, sex drive, and more! It is often referred to as the ‘feel good hormone’ because of its influence over mood and ‘feel good’ activities.

Serotonin is largely produced in your gut, so imbalances in your gut’s microbiome or poor diet can lead to a deficit in your serotonin production. Most pharmaceutical antidepressants are classified as SSRIs, or Selective Serotonin Reuptake Inhibitors. Basically, what that means is that those medications block the reabsorption of serotonin messengers, allowing more of them to remain active in your system. More active serotonin = better mood, less anxiety, better sleep, normal appetite, healthy sex drive, etc.


Bonus! Dopamine can actually be classified as both an inhibitory and excitatory neurotransmitter, it all depends on the kind of dopamine receptor it is binding to!


via Patriot Direct Family Medicine


What Causes Neurotransmitter Imbalance or Deficiency?

Genetics, environment, chemicals (medications, drugs) and nutritional deficiencies are factors that can result in over- or under-production of neurotransmitters. The most common cause, though, is prolonged periods of stress.

Your body’s stress response is a critical survival mechanism, but the realities of modern life have changed the way that we experience stress. Most of us experience moderate stress consistently on a day-to-day basis, with stress levels spiking at certain points, but never really fully subsiding. We aren’t just talking about the obvious kind of stress (work, finances, family), we are also talking about unconscious stress (the blue light from the technology we are always in front of, the constant stream of information being fed to us through those screens, the constant feeling of needing to do “more”, noise pollution, etc.).


This kind of constant low-to-mid grade stress can actually wreak havoc on your system, making ‘fight or flight’ your default mode and significantly altering the balance of those precious neurotransmitters.

Stress triggers a release of cortisol (stress hormone), which signals the release of norepinephrine and flips that ‘fight or flight’ (parasympathetic nervous system) switch to let your brain and body know to batten down the hatches – it’s go time!

The Autonomic Nervous System & Vagus Nerve

In order for your body to do what it is supposed to and flip the switch back to ‘rest and digest’ (sympathetic nervous system), inhibitory neurotransmitters need to be released. Excitatory glutamate should convert to GABA, signaling all is well and that you are safe. This is largely communicated via the vagus nerve, which controls our Autonomic Nervous System (sympathetic and parasympathetic nervous systems) response.

The vagus nerve is also the central communication pathway between the gut and the brain , which is why issues in the gut can so readily manifest as issues of the mind (anxiety, depression, brain fog, fatigue).

Fun fact: deep, belly breathing is so effective at calming you down because it causes your diaphragm to move in a way that activates your vagus nerve to let it know you’re safe.

The vagus nerve, in turn, relays that message to your brain, effectively giving the OK for GABA to be released and the ‘rest and digest’ system to be activated.

autonomic nervous system stress response

Chronic, low grade stress also wreaks havoc on your gut. As mentioned earlier, the gut-brain axis is super important when it comes to managing mental health.

Neurotransmitters like serotonin are largely produced in the gut. You are probably familiar with the idea that stress causes ulcers or that you get an upset stomach when you’re nervous. But when you think about what stress can be doing on a more subtle, daily basis the issue becomes the fact that stress will alter the way that your gut functions and the makeup of your gut microbiome. This can not only result in an imbalance of neurotransmitters like GABA and serotonin, a couple of key inhibitory messengers, but it can also lead to chronic inflammation.

That chronic inflammation is another form of “stress” that needs to be addressed by your body.

You see how this could be an endless cycle and very slippery slope if you’re not careful?

CBD, the Endocannabinoid System & Neurotransmitter Activity

So, what does all of this have to do with CBD and your Endocannabinoid System (ECS)? A lot!

The receptors of your ECS are largely concentrated within your gut and your nervous system aka the two primary systems that are responsible for the production and subsequent activity of neurotransmitters. When you think about the ECS, the most important thing to remember is that its primary goal, above all else, is to create balance. It is the conductor off your body’s orchestra, in charge of ensuring that each individual system is tuned and playing at its best so that when they all come together it creates a beautiful harmony rather than a gross cacophony.

diagram of the endocannabinoid system cb1 and cb2 receptors

ECS receptors can be found at neurotransmitter “firing sites”, so to speak. This prime placement allows them to assess the activity at those sites and make adjustments as necessary. The manner in which the ECS pulls this off is through ‘retrograde signaling’. It is this type of communication and signaling flow that makes the ECS such an epic regulator.

CBD in particular has the ability to affect serotonin activity in the same way as common prescription SSRIs like prozack or zoloft. CBD is able to spur serotonin production and synaptic activity by modulating the signals that are received at the pre and post synaptic sites (the firing and receiving sites). This, along with its ability to increase activate GABA production and up the amount of the endocannabinoid Anandamide active in your system, is what gives CBD its anxiety-relieving powers.

The TONIC Difference

We don’t just rest on the ability of CBD and the ECS to set you straight here at TONIC. We team our hemp extracts up with adaptogens, herbs and superfoods that can help you attain greater neurotransmitter balance.

Ashwagandha (The O.G. and Chill TONIC)

Clinically proven to lower cortisol and modulate activity of the hypothalamus-pituitary axis, which is where hormones like cortisol and adrenaline are produced and released from. Ashwagandha balances HPA activity to help break the stress response cycle you may be caught in. Chronic stress = chronically elevated cortisol = the cascade of negative things mentioned earlier. Changing the stress response by lowering cortisol can stop that cascade in its tracks.

Shop: The O.G. TONIC

Lemon Balm and Passionflower (Chill TONIC)

Inhibit the breakdown of GABA, essentially allowing for more GABA to stay active in your system. Remember: GABA is the body’s brake pedal. When glutamate activity outweighs GABA activity, you are left feeling anxious, stressed and likely without a good night’s sleep.

Shop: Chill TONIC

Black Seed Oil (Flex, The O.G. and Chill TONIC)

The phytochemicals in black seed oil can have a significant impact on your gut health, helping to ensure a healthy balance of gut bacteria. It helps your immune system function at its best, which supports a healthy inflammatory response. Chronic stress = chronic inflammation, so it is important to address both!

Shop: Flex TONIC

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