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Is Histamine Affecting Your Brain? Learn About The Most Effects Histamine Has On The Brain

Histamine, known primarily for its role in allergic reactions, also plays a critical role in the brain, influencing various physiological and cognitive processes. In the central nervous system, histamine acts as a neurotransmitter, modulating functions such as the sleep-wake cycle, cognitive alertness, and stress response. Understanding the effects of histamine on the brain can provide valuable insights into conditions related to mental health, sleep disorders, cognitive performance, and emotional well-being. In today’s article, I will the different ways histamine affects the brain as well as review some of the ways to better balance histamine levels.

How Histamine Affects Your Brain

What is Histamine and How Does It Affect The Brain

Histamine is a signaling chemical your immune system releases to send messages back and forth between different cells. Essentially histamine is how certain cells communicate with one another.

While you may be aware of histamine in relation to allergic reactions like those itchy eyes, runny nose, scratchy throat, and those red blotchy hives in our skin, histamine does so much more than that.

Histamine has a powerful effect on sleep, how your body adapts to stress, and your mood, and today I’m talking about how excess histamine causes problems in the brain. When it comes to histamine, There are 4 known histamine receptors, H1, H2, H3, H4.

The reason why I tell you this is that different tissues have different Histamine receptors and depending on what histamine receptor histamine binds to determines what happens in that tissue.

So, for example, when it comes to the brain, The brain has all 4 histamine receptors. This means histamine can have wide-ranging effects in different parts of our brain depending on where histamine binds.

In the same way that histamine can affect your skin causing hives, and your eyes causing them to water, histamine in the brain can impact things like motivation, memory, mood, and even your appetite. Well, hey there….

I’m Dr Hagmeyer and in today’s video I want to help you understand how histamine can affect your brain, you might be suffering from several problems I will be talking about today and excess histamine may be one of your Root Causes.

One thing I want to be clear on is that histamine is not a bad thing. While most of what bloggers, health enthusiasts, and nutritionists are writing about these days seems to be about histamine intolerance and just how bad histamine is, that’s not entirely the whole story.  As an example, Low histamine levels are associated with convulsions, sleeping disorders, abdominal pain, bloating, seizures, and tics.

Having too much histamine and not having the ability to break it down Now…… that’s is a BAD thing, but I hope by the end of this video, you’re going to think about histamine a bit differently.

As I mentioned, Histamine is a signaling molecule in the gut, the skin, and the immune system BUT in the Brain and nervous system, Histamine is a Neurotransmitter.

If you ever heard of a leaky gut, Histamine can cause a leaky brain, (*) and it can cause nerve cell death, affecting areas of the brain that play a role in appetite, temperature regulation hunger and thirst.

Neuronal histamine (histamine in the brain) can do things like alter blood flow in blood vessels of the brain, this can lead to changes in the blood-brain barrier.  The blood-brain barrier acts as a physical and metabolic barrier (*).

Heres’ why this may be important to you, if you or a loved one is suffering from the residual effects of a stroke, seizures or epilepsy, multiple sclerosis or some other demyelinating, and inflammatory disease that affects the Central Nerve System (*) histamine is a part of this. (*)

Histamine can break down the blood-brain barrier and can cause these problems and many more that I will talk about in today’s video.

Histamine can inhibit the release of serotonin. In fact, in the brain, histamine has been suggested to be a regulator of “whole brain” activity. (*) and so in today’s videos, I’m going to break it down how these things can affect you or your loved ones. Now…

Unlike some of my past videos where I’ve spoken about histamine intolerance being a problem with DAO enzyme, which is the enzyme that breaks down histamine in the gut when we talk about histamine in the brain there are two other enzymes you should know about. One is HNMT and the other is MAOB.

Is Histamine Affecting Your Brain- How HNMT breaks down histamine


The primary function of HNMT is to metabolize histamine by adding a methyl group to it, converting it into N-methylhistamine. This process occurs mainly in the extracellular spaces and intracellular compartments of tissues that contain HNMT, such as the liver, kidneys, lungs, and certain immune cells. While HNMT is responsible for breaking down histamine intracellularly, DAO primarily functions in the extracellular spaces and intestine, breaking down histamine before it enters the bloodstream.

By breaking down histamine, HNMT helps to maintain the balance of histamine levels in the body.


Monoamine oxidase B (MAO-B) is an enzyme primarily located in the brain that plays a role in the breakdown of various neurotransmitters, including dopamine, serotonin, and, to a lesser extent, histamine. While MAO-B is primarily involved in the metabolism of dopamine, it also contributes to the degradation of histamine in the brain.

Problems with either of these can lead to excess histamine in the brain and the reason I tell you this is that you can’t treat excess histamine in the brain the same way you would treat excess histamine in other parts of the body because the enzymes are different. So, I just want you to be aware of that.

Is Histamine Affecting Your Brain- How histamine affects Sleep

1. The Sleep-Wake Cycle

One of the key functions of histamine in the brain is regulating the sleep-wake cycle. Histaminergic neurons in the brainstem are actively involved in promoting wakefulness and maintaining alertness during the day. These neurons release histamine, which acts on various brain regions, including the hypothalamus and cortex, to promote arousal and vigilance. 

In the brain, histamine neurons originate only in the hypothalamus and are thought to play an important role in sleep-wake state stability. In other words, Histamine keeps the mind in a wakened or alert state. You May recognize this as Insomnia or even narcolepsy. Narcolepsy is a chronic neurological disorder that involves a decreased ability to regulate sleep–wake cycles.(*) Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affected also experience episodes of sudden loss of muscle strength.

Studies in animals and humans have shown that histamine neurons help to promote and stabilize wakefulness by:

  • Activating the cortex and wake-promoting neurons outside of the hypothalamus 
  • Inhibiting non-REM sleep–promoting neurons and REM sleep–promoting neurons 

Histamine neurons may play an important role in sustaining wakefulness for long periods during the day. Review study results that suggest increased activation of histamine neurons may help stabilize wakefulness in narcolepsy.

While there are many reasons for sleeping disorders, problems with excess Brain histamine can certainly be a culprit. Many people these days struggle with brain fog and mental fatigue- here again histamine may be a problem.

2. Mental Fatigue and Brain Fog

Histamine’s influence extends beyond sleep regulation to impact cognitive functions such as mental fatigue and brain fog. Adequate histamine levels are crucial for sustaining cognitive alertness, attention, and memory recall. Imbalances in histamine signaling can lead to symptoms of mental fatigue, characterized by decreased cognitive performance, difficulty concentrating, and a sense of cognitive overload. Brain fog, a common complaint among individuals experiencing cognitive impairment, may also be linked to dysregulation in histamine levels.

When histamine receptors are blocked (as in the case of someone taking antihistamines) or if excess histamine is not being properly broken down by its enzymes, we have too much histamine in our brain. This excess again leads to mental fatigue, brain fog, and trouble focusing and concentrating. Think about it this way, if you ever took an antihistamine, like Benadryl how do you typically feel after taking it? Did it make you sleepy and drowsy and affect the way you think, did your heart begin to race, did you experience dizziness or headaches? These are all common side effects of antihistamines. Remember anti-histamines are only blocking how histamine binds to its receptors. It’s not reducing the production of histamine. It’s not addressing the Root Cause.

Another area that we see Histamine affecting is our ability to perceive pain. Are you someone who struggles with chronic pain? Fibromyalgia or CIRS. Mold exposure can trigger mast cell activation syndrome.

How Histamine Affecting Your Brain_ Chronic Pain

3. Pain Perception

Histamine is implicated in the processing of pain signals within the brain. Histaminergic pathways interact with pain perception pathways, modulating the transmission and interpretation of painful stimuli. Changes in histamine activity may influence pain thresholds, sensitivity to pain, and the perception of chronic pain conditions.

In the peripheral nerve system, Histamine is released in response to tissue injury, inflammation, and tissue damage. In the nervous system, when you have too much histamine, it can lead to an increased firing rate of nerves. What this means is that it can generate pain and pain hypersensitivity. So, think about how this may affect people with neuropathy, fibromyalgia or other chronic pain syndromes may be affected by this.

Remember I said that there are 4 kinds of histamine receptors H1, H2, H3, and H4. In the brain, H3 receptors can modulate how pain is transmitted.  Having too much or too little histamine in your brain, you may end up perceiving pain stronger than under normal circumstances (8). But that’s not all those H3 receptors are involved it. Those H3 receptors are involved in mental health problems like ADHD, depression, anxiety, and panic attacks. Histamine stimulates serotonin, norepinephrine, and dopamine transmission in the brain. (*)

I hope by now that you are starting to see just how important Histamine balance in the brain is and just how widespread the effects of histamine are.

If you have been a subscriber on my YouTube channel I have talked a lot about the Fight or flight response in relationship to anxiety and gut issues like SIBO, digestion, and motility disorders. Mental health problems like mood disorders, anxiety disorders and poor stress response can be caused by problems with too much histamine. Histamine is also important when it comes to Neurodegenerative diseases.

Neurodegenerative diseases include  Multiple sclerosis, Alzheimer’s, and Parkinson’s. Too much histamine in the brain can kill nerve cells leading to neurodegeneration. Tourette syndrome has also now been linked to problems with histamine. (*). (*) inhibit the release of HIS, NE, DA, GABA, Glu, and ACh.

Studies have shown that brain histamine can contribute to

  • Vascular changes and alterations in the blood-brain barrier,
  • Changes in immune function within the brain and
  •  Cell death of the nerve cells in the brain.

For those who suffer from anxiety, or panic disorder, Histamine has also been shown to over stimulate specialized receptors called NMDA receptors. (*)

These receptors play a major role in glutamate and GABA balance, brain excitotoxicity and Neurodegeneration. (*) what this means is that histamine is overstimulating the brain and this overstimulating causes the death of nerve cells within the brain

How histamine affects Brain_ Histamine as Neurotransmitter regulator

4. Neurotransmitter Regulator

Histamine is starting to gain some serious attention when it comes to diseases affecting the brain. Histamine is a neurotransmitter or chemical messenger, that affects the function of other neurotransmitters. Histamine is also known as a neuromodulator, since it regulates the release of other neurotransmitters, like acetylcholine, norepinephrine, and serotonin. It acts as an arousal-promoting neurotransmitter by influencing other neurotransmitter systems like norepinephrine, dopamine, and acetylcholine.

It activates histamine receptors (H1 receptors) in the brain, leading to increased alertness and vigilance. It acts as an arousal-promoting neurotransmitter by influencing other neurotransmitter systems like norepinephrine, dopamine, and acetylcholine. It activates histamine receptors (H1 receptors) in the brain, leading to increased alertness and vigilance.

Dopamine and histamine pathways have reciprocal influences on each other. For example, histamine enhances dopamine release in certain brain regions such as the prefrontal cortex and the nucleus accumbens. Dysregulation of this interaction may be associated with conditions like schizophrenia and Parkinson’s disease.

Histamine interacts with the serotonin (5-HT) system in the brain. It can modulate the release of serotonin in certain brain regions, such as the hypothalamus and amygdala. Alterations in histamine-5-HT interactions have been suggested to contribute to psychiatric disorders like depression and anxiety.

How histamine affects Brain and depression

5. Stress Response

Remember that there are different kinds of histamine receptors. There is an H1 receptor in the brain, but this H1 receptor also is found in our adrenal glands. Adrenal glands produce Cortisol, DHEA, adrenaline, and hormones like glucocorticoids.

When this receptor is activated we get a release of those neurotransmitters and hormones like cortisol and adrenaline that prepare our body for fighting or flighting.[*]

The more histamine that is released the more adrenaline and cortisol that we get released as well. In certain individuals, this domino effect can worsen adrenal fatigue.

Cortisol, which is produced by the adrenal glands, is a strong anti-inflammatory hormone, but if you have too much histamine being produced too frequently, your cortisol levels may start to decline.

The more histamine that is released, the more cortisol it takes to counteract the inflammation. The adrenal glands become tired from trying to produce more cortisol- this is what we refer to in functional medicine as adrenal fatigue syndrome.

What about histamine and addiction? This is another interesting area.

6. Alcohol, Drug use, and Addictive behaviors

Histamine may play a role in addictive behaviors like alcohol and drug use. Histamine can either stimulate or inhibit the dopamine system. Dopamine is one of the neurotransmitters that is typically associated with pleasure and reward. We continue to do the things that make us feel good and avoid the things that make us feel bad. This is dopamine!

Histaminergic neurons extend to many areas of the brain, which means that histamine can influence other neurotransmitters. From previous studies, we know that histamine affects serotonin, dopamine, adrenaline, and glutamate.  (*). Histamine also affects hunger and thirst.

7. Weight gain Satiety, Taste Perception, and Feeding Behaviors

Antihistamine can increase our appetite. Histamine decreases our hunger in part affecting the appetite control center in our brains [2], and so it makes sense that when you take antihistamine it would have the opposite effect. It would make you hungry. This can lead to overeating. But that’s not the only way histamine can affect hunger. Histamine affects our leptin levels. Leptin is a hormone that suppresses hunger. When someone becomes leptin-resistant, It can increase binge eating, emotional eating, unhealthy snacking, and disordered eating habits (10). Bet you never thought of histamine as it relates to weight gain.

How histamine affects Brain- Is Your Brain fog causes by Histamine

8. Memory Formation and Cognition

Histamine in the central nervous system helps with learning and memory, remember histamine keeps our mind alert and helps us focus on tasks. This is also why when people take antihistamines for skin or allergies, or itchy runny nose, those antihistamines impair learning and memory.

Histamine has been implicated in learning and memory processes. It can enhance memory consolidation and retrieval, and alterations in histamine levels may affect cognitive functions. Histamine acts on specific receptors, including H2 and H3 receptors, to modulate neurotransmitter release and receptor activity, which subsequently affects learning and memory processes.

While there can be many causes of poor memory- things like gut imbalances, leaky gut, liver dysfunction, SIBO, exposure to toxins, problems with histamine too much or too little can also impact our memory.

9.Motivation and Goal-Setting Behaviors

If you have trouble staying motivated to achieve your goals, histamine may play a role in this as well. Histamine is released during goal-directed actions.

Histamine can modulate the activity of dopamine neurons and influence dopaminergic signaling in brain regions implicated in motivation and reward. By interacting with specific histamine receptors (H3 receptors) in the brain, histamine can regulate the release and synthesis of dopamine. This modulation can have impacts on motivation and reward-seeking behaviors.

Histamine may help to increase goal-seeking behaviors and motivation. However, your histamine levels mustn’t end up too high since that can lead to fatigue and low-energy interfering with your ability to achieve these goals (*).

Some Additional Things To Consider When It Comes To Histamine and The Brain

  1. Support HNMT enzyme function/production (SAMe, B2, B9, B12, magnesium)
  2. Test for Genetic polymorphism or SNPS in the DAO, HNMT, MAOB, and other Neurotransmitter genes.
  3. Vitamins/minerals. Certain Vitamins and minerals like vitamin C, copper, and/or vitamin B6 supplements may help lower histamine levels.
  4. Limiting excitotoxicity in the brain (things Like L-theanine, GABA, zinc, magnesium) GABA and L-theanine increase the amount of a chemical called gamma-aminobutyric acid (GABA) in the brain. GABA helps regulate nerve cells.
  5. A Low glutamate diet might be helpful in a situation like this.
  6. Selenium has been shown to protect against glutamate, and alpha lipoic acid has been shown to covert Glutamate into GABA.
  7. Checking your medications to see if they block DAO or HNMT enzyme (H1 antagonists),
  8. Support Blood Brain Barrier. Resveratrol, Curcumin, Sulforaphane, Vitamin D, Omega 3 fatty acids, Phospholipids, Branched-chain amino acids (BCAAs)

Final thoughts about Histamine and the Brain.

It’s now more apparent more than ever that Histamine affects our entire body. Our brain depends on histamine, but too much or too little can have terrible consequences.

Histamine may lead to poor sleep, increased stress response, increased pain perception, Increased brain fog, compromised neurotransmitter regulation, unhealthy eating behaviors, increased weight, addictive behaviors, poor memory, and low motivation.

There is a lot we still need to uncover about the role histamine plays in our body. There is no simple solution. I get calls every day from people who are following a low histamine diet and taking supplements for histamine intolerance feeling so discouraged. If that’s you don’t feel discouraged. There are many pieces to the histamine puzzle and it’s so much more than just following a low histamine diet especially when you are dealing with the Brain/mental aspects of histamine.

If you are dealing with symptoms of histamine intolerance and related symptoms, and you feel you have hit a brick wall, I invite you to visit my website and learn more about how I work with patients. If you liked today’s video, here’s another video on histamine intolerance, I think you might find interesting.

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