What causes pain? How Histamine Plays a Role…
In this discussion, we’re going to talk about the role that histamine plays in the perpetuation of chronic pain in situations that were originally set off by trauma or a period of chronic, ongoing stress. Histamine is a hormone that works with our boundaries, both emotional and physical. It is a neurohormone that specifically deals with our ability to identify Self and Non-Self. When a person does not feel “safe” in their environment or if that person is not able to create a boundary around themselves to achieve a fully relaxed state on a reliable basis, histamine-related pain or health issues can become a problem.
That being said, humans are a special type of animal. Even when an environment is technically “safe”, our minds and bodies can serve up looping “trauma reels” that play unconsciously. These “trauma reels” that can make us feel unsafe even though we are, indeed, perfectly safe. In other words, trauma from the past that is not properly released can cause the feelings of being traumatized in the present.
In humans, histamine can be released not only in response to actual danger-issues, but also in response to unconscious or perceived danger-issues.
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Chronic Stress, Trauma, the Immune System, and Pain
A number of chronic pain disorders originate from the problem of an over-solicitation of the fight-or-flight system of the body (also known as the Sympathetic Nervous System). When a person (a child or an adult) is under chronic, ongoing stress, or if that person experiences a sudden traumatic experience, the sympathetic nervous system (the fight-of-flight system) can end up in a state of near-constant activation. During states of sympathetic nervous system activation, patients feel pain. Sometimes the pain feels like it’s inside the body and the tissues, sometimes it feels as though it “floats above the skin” in the energy field overlying the actual material body. This state of near-constant activation is punctuated by periods of a parasympathetic “freeze” or “play dead” response that involves extreme lethargy or brain fog and other symptoms associated with chronic fatigue syndrome.The Sympathetic Nervous System in Rheumatic or Fibromyalgia-Type Pain and Chronic Fatigue Syndrome
The sympathetic nervous system is just one branch of the Autonomic Nervous System (ANS). The ANS is a part of the central nervous system that deals with unconscious control over organs, circulation, and all aspects of our bodily function that we don’t consciously regulate. The ANS is made up of four branches:
- Sympathetic Nervous System Branches
- Alpha-Sympathetic - awake and aware, but in a state of relative relaxation.
- Beta-Sympathetic - fight-or-flight
- Parasympathetic Nervous System Branches
- Dorsal Parasympathetic - “freeze” responses involving lethargy and brain fog
- Ventral Parasympathetic - rest-and-digest states of rejuvenation
Conventional medicine only recognizes two branches of the ANS: the sympathetic nervous system and the parasympathetic nervous system. As such, conventional medicine literally does not have a workable model of the nervous system that would make it possible to heal chronic pain syndromes like fibromyalgia, rheumatism, or chronic fatigue syndrome. The two branches of the sympathetic nervous system that we discuss here are part of a model of medicine known as “endobiogeny”. The two branches of the parasympathetic nervous system that we discuss here are part of a model set forth by Dr. Stephen Porges to describe “play dead” or “freeze” states that involve symptoms such as exhaustion, fever, brain fog, upset stomach, achiness or pain, depression, and other low-energy feelings of being “drained”.
Our bodies are designed to do rest-and-digest in order to repair and rejuvenate in order to prevent wear-and-tear on our organs and tissues, but if a person has experienced chronic, long-term stress or a major traumatic event (or multiple traumatic events that are never released and integrated using trauma-informed therapies or the sacred medicines), the rest-and-digest function that’s controlled by the ventral parasympathetic branch can get hijacked. When this happens, histamine release is increased. When histamine release is increased to pathological levels, histamine begins to act on its own instead of acting in concert with the four branches of the ANS.
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Histamine
Histamine is not always bad. In fact, histamine does a lot of good things in the body:- Histamine is a signaling molecule that’s found naturally in plants and animals.
- Histamine regulates:
- Digestion
- Sexual function
- Sleep
- Blood pressure
- Neurotransmission
- Histamine balances our adaptation and arousal response to stressful stimuli.
Trauma is something that, when triggered, will make use feel as we did in a traumatic moment from the past. These trauma-based feelings involve a shift in histamine where histamine is no longer chronologically synchronized with our normal adaptation and arousal response system (which involves adrenaline and serotonin as important players). Trauma, essentially, causes the body (specifically, the autonomic nervous system and the endocrine system), to become de-synchronized. We experience the past in the present tense as feelings that are identical to feelings that we felt in the past except they’re “stuck”. They lack the natural “arc” of a healthy present-tense emotion.
Histamine, normally functions in the body to synchronize different levels of arousal. In one moment, we might be startled by a loud noise. The body might go into an alpha-sympathetic state of pre-fight-or-flight. In this alpha-sympathetic state, we tune into the environment to check for additional signs of danger. A normal, healthy, non-traumatized person might hear the loud noise and tune in for a few minutes and then return to a state of rest-and-digest (ventral parasympathetic) to continue with what they were doing. But a person who has trauma in their body might go straight from a dorsal parasympathetic state of “freeze” or “play dead” to a beta-sympathetic fight-or-flight state. This happens when histamine is not tethering the adrenaline response to serotonin anymore. A person who has an untethered histamine response will become hyper-reactive to the environment.
Essentially, when histamine levels are too high and not properly tethered into the arousal sequence, the person’s body will stop being able to recognize Non-Self and begin attack Self. This may begin as an emotional issue. It can sound like judgmental or toxic thoughts and mental chatter that’s hard to control sometimes. But it can also turn into issues like cancer, diabetes, chronic pain, autoimmunity, dementia, psychosis, severe mood problems and mental illness, and any chronic, long-term disease state that involves degeneration or nervous system malfunction.
Histamine is an autocoid (as sometimes referred to as a “paracrine” in some models) that’s created from the amino acid histidine. This means that histamine works locally as a hormone in the body. Its effects are supposed to be transient and local (meaning that it typically impacts just one region of the body), but when the sympathetic nervous system is in a state of chronic activation or exaggerated expression, histamine can be overexpressed in an ongoing, abnormal way that, in turn, causes the normal adaptation and arousal cycle to become pathological in terms of exaggerated and delayed responses. In other words, the body begins to over-react as a result of the constant presence of histamine and the timing of histamine release can become disrupted by chronic stress or trauma that isn’t properly released and integrated. Histamine receptor production is upregulated by chronic stress and trauma such that histamine becomes too powerful in the body. It can stop acting locally when provoked and begin having a broader sphere of influence inside the body, a situation that looks like Mast Cell Activation Syndrome, rheumatism, arthritis, fibromyalgia, chronic fatigue syndrome, Post Traumatic Stress Disorder, mental illness, allergies, and more.
But histamine itself is not intelligent, per se. Indeed, a more apt focal point might be the cells that produce histamine. The following cells produce histamine in the human body:
- Mast Cells - These are a type of white blood cell that’s found in connective tissues throughout the body. Mast cells are found in relatively small numbers in the connective tissues under normal circumstances. Mast cells can migrate to different locations in the body, as needed and then mature and receive information from T-cells about antigens found on invading pathogens.
- Basophils - These are another type of white blood cell that’s less common than mast cells. In contrast to mast cells, basophils are found in blood. Like mast cells, they can also rapidly migrate to areas of the body where they’re needed. An influx of basophils is usually accompanied by a simultaneous influx of Th2 lymphocytes and eosinophilic granulocytes. Basophils often show up too late to address allergens directly – they tend to arrive several hours after allergen exposure, and many scientists believe that by the time basophils arrive, allergens have cleared.
- Eosinophils - Eosinophils interact with mast cells in the late stages of an allergic reaction.
- Enterochromaffin-like Cells - Enterochromaffin-like cells in the stomach produce histamine which, in turn, stimulates the release of gastric acids for the digestion of food.
- Neurons - Certain neurons in the central nervous system and digestive tract produce histamine.
- Platelets - Platelets can produce histamine in small amounts.
While histamine often becomes a focal point for patients who are trying to get rid of fibromyalgia, rheumatic disease, severe allergies, and other health issues, in fact, histamine is not “intelligent” per se. It is, however, a visible manifestation of a particular response in the body by intelligent cells. It should be noted, however, that while the immune system might seem intelligent, as a system, it is largely government by other endocrine glands. It doesn’t tend to operate intelligently without receiving orders from the endocrine system, especially the corticotropic axis (the endocrine axis that produces steroids that reduce inflammation, for example) and the thyrotropic axis (the endocrine axis that includes the thyroid gland and the thymus gland).
All of this may seem hopelessly complicated for anyone who is not an immunologist and indeed, it is complicated if we focus exclusively on histamine without considering the macroscopic aspects of the human body. Histamine has become a focal point in the treatment of allergies and other health issues because of antihistamines as drugs. The word “antihistamine” entered the common vernacular in the English language more than 70 years ago with the development of diphenhydramine / Benadryl. By the 1950s there were over 20 antihistamine drugs being marketed. So people are familiar with “histamine” as a potentially problematic thing for which antihistamines can be useful. But histamines are merely a thing that’s produced and then released by higher-level cells such as mast cells or platelets.
Antihistamines: Safety and Effectiveness at Reducing Histamine Levels
There isn’t a great deal of research into antihistamine safety and effectiveness. Most of the studies into antihistamine drugs are short-term and most of them use a very small sample size and they make broad-sweeping general assumptions. There are no studies showing how antihistamines impact people with long-term histamine-related issues such as allergies who take antihistamine drugs for a long period of time. No studies exist to compare the effectiveness of the various antihistamine drugs that are currently on the market.
First generation antihistamines are also anticholinergic medications. Studies have shown that the anticholinergic effects are associated with a heightened risk of dementia and cognitive decline in older patients.
Iodine Deficiency and Pain Disorders
For many people who have chronic pain due to arthritis, fibromyalgia, chronic fatigue syndrome, or any number of disease states involving inflammation, iodine deficiency is a major problem that contributes to chronic pain. In the modern world, iodine deficiency almost never exists in vacuum – it is typically accompanied by bromide and fluoride toxicity as these two substances masquerade in the body as iodine and hijack the thyroid gland and in turn, the thymus gland. Often people experience a significant boost in energy and also improved pain control after they get through the detoxification from toxic halide exposure after regular supplementation with Lugol’s iodine 2% for 30-60 days.The thymus gland is essential in proper immune function. Indeed, the thymus gland is one of just a few essential organs / glands of the immune system. B lymphocytes that originate in the bone marrow (“B” for Bone) migrate to the thymus gland to go through “military training” in this gland that’s located behind the sternum to become T lymphocytes (“T” for Thymus). The B lymphocytes that make the cut (not all of them do) are rewarded with T cell status. T cells that make it through the training process in the thymus gland are then able to police the body looking for pathogens. When they find a pathogen, their job is to grab an antigen off that pathogen that they can then present to a mast cell. Mast cells then choose from an arsenal of weapons and tools to decide how to respond to the threat. Histamine is one of the tools that mast cells can use to overcome a pathogen invasion.
The thymus gland is like a military base in the body where T lymphocytes are vetted and trained from a pool of elite B lymphocytes fresh from the bone marrow. Humoral factors produced in the thymus gland are essential for the maturation and development of T lymphocytes, which act as “soldiers” that stand sentinel against invading pathogens. But the humoral factors that play such an important role in thymus gland activity are regulated by thyroid hormones. For example, if the thyroid gland is hyperfunctioning (hyperthyroid), the thymic humoral factor known as “thymulin” will be too high. If the thyroid gland is hypofunctioning (hypothyroid), then thymulin levels will be too low.
Histamine as an Endocrine Regulator
The tuberomamillary nucleus (TMN) is an area of the hypothalamus where histamine neurons produce histamine. Histamine in this area is catalyzed by the enzyme histidine decarboxylase which deconstructs the amino acid histidine into histamine. On the other hand, histamine is deactivated into an inactive form (tele-methylhistamine / t-MeHA) by the enzyme N-methyltransferase.All histamine receptor types are G-protein coupled. The histamininergic system involves four histamine receptor types, H1 to H4.
The histaminergic system controls the following physiological functions:
- Sleep-wake cycles
- Energy homeostasis
- Endocrine homeostasis
- Sensory functions
- Motor functions
- Cognitive functions
- Learning
- Attention
- Memory
Dysfunction of the histaminergic system can contribute to the following disorders including:
- Alzheimer’s disease
- Parkinson’s disease
- Narcolepsy
- Schizophrenia
- Tourette syndrome
- Autism / ASD
- Depression
- Insomnia
Normally, histamine is produced when a person switches to alpha-sympathetic activation from ventral parasympathetic activation. Serotonin is an autocoid that prolongs ventral parasympathetic activation. Serotonin, in a sense, opposes the action of histamine as a promoter of the alpha-sympathetic activation state. Histamine is released at the very beginning of the activation of an alpha-symapthetic state to prolong alpha-sympathetic activation. So while serotonin promotes and prolongs a rest-and-digest state, in order to prevent over-reactivity of the human organism, histamine is a substance that’s released to maintain alpha-sympathetic activation and prevent, up to a point, the activation of a beta-sympathetic response / fight-or-flight. Another way to look at this idea is to say that histamine is released in an effort to prevent “over-reaction” of the physical body to a perceived threat. But once an over-reaction occurs, if that over-reaction is stimulated by additional trauma or by prolonged and chronic stress, histamine becomes “unhinged” from the triggers such that it becomes an instigator of endocrine system imbalance rather than the agent that keeps the symphony of hormones that deal with adaptation and arousal, in tune and synced up.
Unfortunately, when histamine receptors are increased to a point of critical mass in one or more areas of the body, histamine begins acting as an autonomous hormone that can activate alpha-sympathetic states when they’re not appropriate or needed.
The important takeaway here about histamine, in the context of trauma or exposure to chronic stress, is that this neurohormone acts to produce not only physical symptoms of distress (chronic pain, symptoms of allergy, and autoimmune disease), but also symptoms of psychological and emotional distress (dementia, psychosis, depression, ASD, and more). So while it’s true that histamine is not “intelligent” as a neurohormone. Histamine acts more like a very flexible “hinge” or “pivot” that keeps the endocrine hormones tethered together and working in harmonious unison.
If histamine is disrupted though, this neurohormone seems to act as the instigator of endocrine anarchy. Any number of physical or psychological disorders can develop when histamine is “unhinged”. Once histamine is untethered from the adaptation-arousal cycle and endocrine balance occurs, increasing or reducing histamine levels won’t help. What matters is the rhythm and duration of histamine release, not the amount of histamine in the body. To reduce histamine levels can actually cause endocrine imbalances too. To increase histamine levels creates a similar set of issues.
In order to restore order in the body, we have to look at the endocrine system and the autonomic nervous system in an entirely different way.
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Histamine Intolerance and Fibromyalgia and Chronic Fatigue Syndrome
“Histamine intolerance” is the buzz phrase used to describe the problem of having histamine that’s gone rogue and that’s no longer coordinated into a normal, controlled “reactionary moment” in the human experience. In other words, if you’ve experienced prolonged stress or a major trauma (or many major traumas) in your life, you might be experience flight-or-flight / beta-sympathetic states too often. These fight-or-flight feelings might not be synced up with your actual experience in the present moment. You might, for example, have anxiety or panic for no reason that you can readily identify. Your body may go from a resting state quickly into a fight-or-flight state and your histamine levels might be untethered from the symphony of other hormones that normally work in concert with it. In psychology, this is called Post Traumatic Stress Disorder (PTSD), but you don’t have to paste this label to your forehead. To simply say that you have trauma that has not been properly released yet is an acceptable way of putting the experience of being out-of-sync with the present moment into words.Pain disorders like rheumatism, fibromyalgia, and chronic fatigue syndrome seem to have no biological origin in part because they are rooted in trauma and derived from the body’s normal trauma response. Trauma and trauma-informed therapies are a field that deals with the mind-body connection, namely the autonomic nervous system and the endocrine system. While trauma-informed therapists rarely discuss things like an exaggerated histamine response with their clients, in fact, histamine “intolerance” (a misnomer) is something that becomes a focal point when clients get to the end of trauma-release therapy using sacred indigenous medicines like psilocybin, Ayahuasca, or Iboga.
In order to understand the histamine response, we have to step away from mainstream science and look at histamine from a totally different perspective. What if, as humans, we have the ability to feel other people using our bodies and not our narrative, logical minds? What if we are energetically connected to other people in a way that can cause us to energetically respond or react to them?
And what if we have the ability, as humans, to send our consciousness to other “realms” that are only tenuously connected to the present tense? What if PTSD and trauma-related dissociation is actually like breaking energy away from the consciousness of the human organism to leave it in a past-tense moment of trauma or to send it into future-tense planning projects in an effort to escape from the mess of the present moment? For example, let’s say that a young adult person is in a serious car accident that’s traumatic. Let’s imagine that this person was on their way to a birthday party. Though this trauma could be released using a variety of techniques, we are no longer schooled in these methods in modern society and we don’t use them. The trauma of experiencing this car accident, thus causes the person to leave a part of their energy, their consciousness in the past where it re-lives the accident over and over again. This person experiences flashbacks or emotional “vortices” of the fear they felt during the accident every time they are exposed to birthdays, birthday party supplies, or anything birthday related that they might see online or on TV.
This hypothetical person would be triggered often by birthday-related material because birthdays are common and birthday supplies are seen in a number of contexts. So this person develops a phobia about birthdays and birthday parties. To cope with it, this person might avoid all of the big box stores or any location where birthday supplies are sold. The person might also develop a generalized anxiety disorder or even depression or psychosis. Physical symptoms of disease might develop, in part, to help this person notice that their body is suffering. This person might develop an autoimmune disease that creates a type of incapacitation that makes it easier for the person to avoid birthday-related material.
This is an over-simplified hypothetical situation, but it depicts how we try to cope with trauma when trauma isn’t properly released within a timely manner. Click here to read more about a real-life scenario involving trauma and how the triggers and unconscious material was portrayed in everyday, conscious life.
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Overcome Fibromyalgia Naturally by Targeting the Histaminergic System
Scientists have demonstrated already that there’s a direct connection between fibromyalgia and overactive mast cells. But in a lot of the content online about fibromyalgia and overactive mast cells, the mast cells are cast as the problematic focus driving the chronic pain. While mast cells are, in fact, one type of cell that produces and releases histamine, leukocytes, and enterochromaffin cells in the stomach also release histamine. And an elevated histamine release is caused, in the initial stages of fibromyalgia development, by chronic, ongoing alpha-sympathetic states. In other words, elevated histamine release is caused by chronic, ongoing stress, or by the buildup of moderate or major traumatic experiences that have not been released by the body.
In a normal, healthy cycle of arousal and adaptation, we begin in a rest-and-digest state. This state is supported and prolonged by the release of serotonin in the gut and in the brain. If something happens in our environment, we launch into an alpha-sympathetic state which is supported and prolonged by histamine. If this level of arousal is elevated to fight-or-flight (beta-sympathetic), histamine, at normal levels in the body will help to return the body back to a brief state of first, dorsal parasympathetic “freeze” response, and then into a state of ventral parasympathetic rest-and-digest.
When a person has been chronically stressed or even chronically triggered in terms of their traumas from the past, the alpha-sympathetic state gets prolonged and histamine levels are elevated as a result. For a while, histamine remains dependent on adrenaline and other hormones that spur the alpha-sympathetic state to calm down, but over time, if the pattern of prolonged alpha-sympathetic continues, human tissues begin to produce more and more histamine receptors. In other words, the body listens to the urgency of the demand that’s being produced by stress or trauma. The body or, in other words, the autonomic nervous system creates a milieu for histamine to begin acting on its own without solicitation from the arousal and adaptation cycle.
If histamine levels are elevated in this way, histamine will begin to prolong alpha-states in a way that increases the release of adrenaline. Adrenaline release will be delayed too and also exaggerated in terms of the severity of the adrenal response. This creates and perpetuates the problem of being “out of sync” with environmental cues about time (sunrise, sunset, moon phases, seasons, etc.) and also social cues (that would normally promote a rejuvenative and restorative rest-and-digest parasympathetic state). At this stage in the development of fibromyalgia, histamine acts to produce pain that sometimes feels like it’s in the body, sometimes like it’s floating over the body.
Histamine is produced in the stomach by enterochromaffin cells and as the body starts to heal from fibromyalgia, some patients notice that their internal organs, specifically the stomach, is upset and somehow involved in producing the pain.
Like fibromyalgia and chronic fatigue syndrome, allergies are driven by elevated and unhinged histamine release that’s no longer hooked into the trajectory of the human arousal and adaptation cycle. To overcome fibromyalgia and chronic fatigue syndrome, you’ll have to release your trauma using the sacred indigenous medicines. This can be a long process (it usually takes 1-2 years depending on the patient profile) to produce a permanent cure for fibromyalgia and chronic fatigue syndrome. Patients experience landmarks of progress as they work toward the permanent goal with emotional relief happening first, followed by a slow but steady “retethering” of histamine to the arousal sequence to the adrenal and serotonergic response again.
To learn more about how to work with the sacred medicines to overcome MCAS, set up a health coaching session with us here.
Also, click here to learn more about nicotine patches and amanita muscaria, both of which work very well to naturally cure fibromyalgia, particularly when the patient also works to release trauma as a part of the protocol.
How to Cure Mast Cell Activation Syndrome (MCAS) via Histamine Tethering
In Mast Cell Activation Syndrome (MCAS), people often experience postural orthostatic tachycardia syndrome (POTS) when their body fails to time the shift from a parasympathetic rest-and-digest state (a seated position) to an alpha-symapthetic state that’s more active (standing). As we discussed above, histamine tethers one state of arousal to another to make a smooth adjustment from rest-and-digest (or “freeze” / “play dead”) to “fight-or-flight”, etc. Flushing and shortness of breath is an alpha-sympathetic or a beta-sympathetic phenomena. Symptoms such as headaches, skin rashes, excessive urination, light-headedness, gastrointestinal symptoms, and even vomiting can all be traced back to this overzealous arousal response that’s normally tightly regulated and kept balanced by histamine.The frustrating thing about MCAS is that it is experienced as a physical disease, but it often begins as a result of an emotional trauma. To retether the histamine response back into the arousal sequence properly, you have to work with mind-body medicines like Ayahuasca, psilocybin, or San Pedro. Working with the sacred medicines can provide a permanent cure for MCAS, but it takes work and persistence. To learn more about how to work with the sacred medicines to overcome MCAS, set up a health coaching session with us here.
Summary
If you aren't ready to work with the sacred medicines to release trauma in order to cure fibromyalgia, chronic fatigue, chronic pain syndromes, or MCAS, start by working with the DreamLight.app, a brain entrainment and guided meditation tool as an alternative that gives you the power to release trauma using at-home treatments.
Click here to learn more about the DreamLight.app, a guided meditation and brain-entrainment tool.
Many people use the DreamLight.app in tandem with Eye Movement Desensitization and Reprocessing / EMDR, another at-home trauma-release tool. EMDR and the DreamLight.app are not nearly as powerful as psilocybin or Ayahuasca for trauma-release, but many people begin their journey by working with these tools. Craniosacral therapy can also be extremely valuable as a tool to release deep trauma that's resistant to the DreamLight.app or EMDR.
Click here to do a free trial of EMDR online.
Resources:
• Hedayat, K. M. & Lapraz, J. C. (2019). The Theory of Endobiogeny: Volume 1. Academic Press: London.
In this discussion, we’re going to talk about the role that histamine plays in the perpetuation of chronic pain in situations that were originally set off by trauma or a period of chronic, ongoing stress. Histamine is a hormone that works with our boundaries, both emotional and physical. It is a neurohormone that specifically deals with our ability to identify Self and Non-Self. When a person does not feel “safe” in their environment or if that person is not able to create a boundary around themselves to achieve a fully relaxed state on a reliable basis, histamine-related pain or health issues can become a problem.
That being said, humans are a special type of animal. Even when an environment is technically “safe”, our minds and bodies can serve up looping “trauma reels” that play unconsciously. These “trauma reels” that can make us feel unsafe even though we are, indeed, perfectly safe. In other words, trauma from the past that is not properly released can cause the feelings of being traumatized in the present.
In humans, histamine can be released not only in response to actual danger-issues, but also in response to unconscious or perceived danger-issues.
The sympathetic nervous system is just one branch of the Autonomic Nervous System (ANS). The ANS is a part of the central nervous system that deals with unconscious control over organs, circulation, and all aspects of our bodily function that we don’t consciously regulate. The ANS is made up of four branches:
Conventional medicine only recognizes two branches of the ANS: the sympathetic nervous system and the parasympathetic nervous system. As such, conventional medicine literally does not have a workable model of the nervous system that would make it possible to heal chronic pain syndromes like fibromyalgia, rheumatism, or chronic fatigue syndrome. The two branches of the sympathetic nervous system that we discuss here are part of a model of medicine known as “endobiogeny”. The two branches of the parasympathetic nervous system that we discuss here are part of a model set forth by Dr. Stephen Porges to describe “play dead” or “freeze” states that involve symptoms such as exhaustion, fever, brain fog, upset stomach, achiness or pain, depression, and other low-energy feelings of being “drained”.
Our bodies are designed to do rest-and-digest in order to repair and rejuvenate in order to prevent wear-and-tear on our organs and tissues, but if a person has experienced chronic, long-term stress or a major traumatic event (or multiple traumatic events that are never released and integrated using trauma-informed therapies or the sacred medicines), the rest-and-digest function that’s controlled by the ventral parasympathetic branch can get hijacked. When this happens, histamine release is increased. When histamine release is increased to pathological levels, histamine begins to act on its own instead of acting in concert with the four branches of the ANS.
Trauma is something that, when triggered, will make use feel as we did in a traumatic moment from the past. These trauma-based feelings involve a shift in histamine where histamine is no longer chronologically synchronized with our normal adaptation and arousal response system (which involves adrenaline and serotonin as important players). Trauma, essentially, causes the body (specifically, the autonomic nervous system and the endocrine system), to become de-synchronized. We experience the past in the present tense as feelings that are identical to feelings that we felt in the past except they’re “stuck”. They lack the natural “arc” of a healthy present-tense emotion.
Histamine, normally functions in the body to synchronize different levels of arousal. In one moment, we might be startled by a loud noise. The body might go into an alpha-sympathetic state of pre-fight-or-flight. In this alpha-sympathetic state, we tune into the environment to check for additional signs of danger. A normal, healthy, non-traumatized person might hear the loud noise and tune in for a few minutes and then return to a state of rest-and-digest (ventral parasympathetic) to continue with what they were doing. But a person who has trauma in their body might go straight from a dorsal parasympathetic state of “freeze” or “play dead” to a beta-sympathetic fight-or-flight state. This happens when histamine is not tethering the adrenaline response to serotonin anymore. A person who has an untethered histamine response will become hyper-reactive to the environment.
Essentially, when histamine levels are too high and not properly tethered into the arousal sequence, the person’s body will stop being able to recognize Non-Self and begin attack Self. This may begin as an emotional issue. It can sound like judgmental or toxic thoughts and mental chatter that’s hard to control sometimes. But it can also turn into issues like cancer, diabetes, chronic pain, autoimmunity, dementia, psychosis, severe mood problems and mental illness, and any chronic, long-term disease state that involves degeneration or nervous system malfunction.
Histamine is an autocoid (as sometimes referred to as a “paracrine” in some models) that’s created from the amino acid histidine. This means that histamine works locally as a hormone in the body. Its effects are supposed to be transient and local (meaning that it typically impacts just one region of the body), but when the sympathetic nervous system is in a state of chronic activation or exaggerated expression, histamine can be overexpressed in an ongoing, abnormal way that, in turn, causes the normal adaptation and arousal cycle to become pathological in terms of exaggerated and delayed responses. In other words, the body begins to over-react as a result of the constant presence of histamine and the timing of histamine release can become disrupted by chronic stress or trauma that isn’t properly released and integrated. Histamine receptor production is upregulated by chronic stress and trauma such that histamine becomes too powerful in the body. It can stop acting locally when provoked and begin having a broader sphere of influence inside the body, a situation that looks like Mast Cell Activation Syndrome, rheumatism, arthritis, fibromyalgia, chronic fatigue syndrome, Post Traumatic Stress Disorder, mental illness, allergies, and more.
But histamine itself is not intelligent, per se. Indeed, a more apt focal point might be the cells that produce histamine. The following cells produce histamine in the human body:
While histamine often becomes a focal point for patients who are trying to get rid of fibromyalgia, rheumatic disease, severe allergies, and other health issues, in fact, histamine is not “intelligent” per se. It is, however, a visible manifestation of a particular response in the body by intelligent cells. It should be noted, however, that while the immune system might seem intelligent, as a system, it is largely government by other endocrine glands. It doesn’t tend to operate intelligently without receiving orders from the endocrine system, especially the corticotropic axis (the endocrine axis that produces steroids that reduce inflammation, for example) and the thyrotropic axis (the endocrine axis that includes the thyroid gland and the thymus gland).
All of this may seem hopelessly complicated for anyone who is not an immunologist and indeed, it is complicated if we focus exclusively on histamine without considering the macroscopic aspects of the human body. Histamine has become a focal point in the treatment of allergies and other health issues because of antihistamines as drugs. The word “antihistamine” entered the common vernacular in the English language more than 70 years ago with the development of diphenhydramine / Benadryl. By the 1950s there were over 20 antihistamine drugs being marketed. So people are familiar with “histamine” as a potentially problematic thing for which antihistamines can be useful. But histamines are merely a thing that’s produced and then released by higher-level cells such as mast cells or platelets.
There isn’t a great deal of research into antihistamine safety and effectiveness. Most of the studies into antihistamine drugs are short-term and most of them use a very small sample size and they make broad-sweeping general assumptions. There are no studies showing how antihistamines impact people with long-term histamine-related issues such as allergies who take antihistamine drugs for a long period of time. No studies exist to compare the effectiveness of the various antihistamine drugs that are currently on the market.
First generation antihistamines are also anticholinergic medications. Studies have shown that the anticholinergic effects are associated with a heightened risk of dementia and cognitive decline in older patients.
The thymus gland is essential in proper immune function. Indeed, the thymus gland is one of just a few essential organs / glands of the immune system. B lymphocytes that originate in the bone marrow (“B” for Bone) migrate to the thymus gland to go through “military training” in this gland that’s located behind the sternum to become T lymphocytes (“T” for Thymus). The B lymphocytes that make the cut (not all of them do) are rewarded with T cell status. T cells that make it through the training process in the thymus gland are then able to police the body looking for pathogens. When they find a pathogen, their job is to grab an antigen off that pathogen that they can then present to a mast cell. Mast cells then choose from an arsenal of weapons and tools to decide how to respond to the threat. Histamine is one of the tools that mast cells can use to overcome a pathogen invasion.
The thymus gland is like a military base in the body where T lymphocytes are vetted and trained from a pool of elite B lymphocytes fresh from the bone marrow. Humoral factors produced in the thymus gland are essential for the maturation and development of T lymphocytes, which act as “soldiers” that stand sentinel against invading pathogens. But the humoral factors that play such an important role in thymus gland activity are regulated by thyroid hormones. For example, if the thyroid gland is hyperfunctioning (hyperthyroid), the thymic humoral factor known as “thymulin” will be too high. If the thyroid gland is hypofunctioning (hypothyroid), then thymulin levels will be too low.
All histamine receptor types are G-protein coupled. The histamininergic system involves four histamine receptor types, H1 to H4.
The histaminergic system controls the following physiological functions:
Dysfunction of the histaminergic system can contribute to the following disorders including:
Normally, histamine is produced when a person switches to alpha-sympathetic activation from ventral parasympathetic activation. Serotonin is an autocoid that prolongs ventral parasympathetic activation. Serotonin, in a sense, opposes the action of histamine as a promoter of the alpha-sympathetic activation state. Histamine is released at the very beginning of the activation of an alpha-symapthetic state to prolong alpha-sympathetic activation. So while serotonin promotes and prolongs a rest-and-digest state, in order to prevent over-reactivity of the human organism, histamine is a substance that’s released to maintain alpha-sympathetic activation and prevent, up to a point, the activation of a beta-sympathetic response / fight-or-flight. Another way to look at this idea is to say that histamine is released in an effort to prevent “over-reaction” of the physical body to a perceived threat. But once an over-reaction occurs, if that over-reaction is stimulated by additional trauma or by prolonged and chronic stress, histamine becomes “unhinged” from the triggers such that it becomes an instigator of endocrine system imbalance rather than the agent that keeps the symphony of hormones that deal with adaptation and arousal, in tune and synced up.
Unfortunately, when histamine receptors are increased to a point of critical mass in one or more areas of the body, histamine begins acting as an autonomous hormone that can activate alpha-sympathetic states when they’re not appropriate or needed.
The important takeaway here about histamine, in the context of trauma or exposure to chronic stress, is that this neurohormone acts to produce not only physical symptoms of distress (chronic pain, symptoms of allergy, and autoimmune disease), but also symptoms of psychological and emotional distress (dementia, psychosis, depression, ASD, and more). So while it’s true that histamine is not “intelligent” as a neurohormone. Histamine acts more like a very flexible “hinge” or “pivot” that keeps the endocrine hormones tethered together and working in harmonious unison.
If histamine is disrupted though, this neurohormone seems to act as the instigator of endocrine anarchy. Any number of physical or psychological disorders can develop when histamine is “unhinged”. Once histamine is untethered from the adaptation-arousal cycle and endocrine balance occurs, increasing or reducing histamine levels won’t help. What matters is the rhythm and duration of histamine release, not the amount of histamine in the body. To reduce histamine levels can actually cause endocrine imbalances too. To increase histamine levels creates a similar set of issues.
In order to restore order in the body, we have to look at the endocrine system and the autonomic nervous system in an entirely different way.
Pain disorders like rheumatism, fibromyalgia, and chronic fatigue syndrome seem to have no biological origin in part because they are rooted in trauma and derived from the body’s normal trauma response. Trauma and trauma-informed therapies are a field that deals with the mind-body connection, namely the autonomic nervous system and the endocrine system. While trauma-informed therapists rarely discuss things like an exaggerated histamine response with their clients, in fact, histamine “intolerance” (a misnomer) is something that becomes a focal point when clients get to the end of trauma-release therapy using sacred indigenous medicines like psilocybin, Ayahuasca, or Iboga.
In order to understand the histamine response, we have to step away from mainstream science and look at histamine from a totally different perspective. What if, as humans, we have the ability to feel other people using our bodies and not our narrative, logical minds? What if we are energetically connected to other people in a way that can cause us to energetically respond or react to them?
And what if we have the ability, as humans, to send our consciousness to other “realms” that are only tenuously connected to the present tense? What if PTSD and trauma-related dissociation is actually like breaking energy away from the consciousness of the human organism to leave it in a past-tense moment of trauma or to send it into future-tense planning projects in an effort to escape from the mess of the present moment? For example, let’s say that a young adult person is in a serious car accident that’s traumatic. Let’s imagine that this person was on their way to a birthday party. Though this trauma could be released using a variety of techniques, we are no longer schooled in these methods in modern society and we don’t use them. The trauma of experiencing this car accident, thus causes the person to leave a part of their energy, their consciousness in the past where it re-lives the accident over and over again. This person experiences flashbacks or emotional “vortices” of the fear they felt during the accident every time they are exposed to birthdays, birthday party supplies, or anything birthday related that they might see online or on TV.
This hypothetical person would be triggered often by birthday-related material because birthdays are common and birthday supplies are seen in a number of contexts. So this person develops a phobia about birthdays and birthday parties. To cope with it, this person might avoid all of the big box stores or any location where birthday supplies are sold. The person might also develop a generalized anxiety disorder or even depression or psychosis. Physical symptoms of disease might develop, in part, to help this person notice that their body is suffering. This person might develop an autoimmune disease that creates a type of incapacitation that makes it easier for the person to avoid birthday-related material.
This is an over-simplified hypothetical situation, but it depicts how we try to cope with trauma when trauma isn’t properly released within a timely manner. Click here to read more about a real-life scenario involving trauma and how the triggers and unconscious material was portrayed in everyday, conscious life.
Scientists have demonstrated already that there’s a direct connection between fibromyalgia and overactive mast cells. But in a lot of the content online about fibromyalgia and overactive mast cells, the mast cells are cast as the problematic focus driving the chronic pain. While mast cells are, in fact, one type of cell that produces and releases histamine, leukocytes, and enterochromaffin cells in the stomach also release histamine. And an elevated histamine release is caused, in the initial stages of fibromyalgia development, by chronic, ongoing alpha-sympathetic states. In other words, elevated histamine release is caused by chronic, ongoing stress, or by the buildup of moderate or major traumatic experiences that have not been released by the body.
In a normal, healthy cycle of arousal and adaptation, we begin in a rest-and-digest state. This state is supported and prolonged by the release of serotonin in the gut and in the brain. If something happens in our environment, we launch into an alpha-sympathetic state which is supported and prolonged by histamine. If this level of arousal is elevated to fight-or-flight (beta-sympathetic), histamine, at normal levels in the body will help to return the body back to a brief state of first, dorsal parasympathetic “freeze” response, and then into a state of ventral parasympathetic rest-and-digest.
When a person has been chronically stressed or even chronically triggered in terms of their traumas from the past, the alpha-sympathetic state gets prolonged and histamine levels are elevated as a result. For a while, histamine remains dependent on adrenaline and other hormones that spur the alpha-sympathetic state to calm down, but over time, if the pattern of prolonged alpha-sympathetic continues, human tissues begin to produce more and more histamine receptors. In other words, the body listens to the urgency of the demand that’s being produced by stress or trauma. The body or, in other words, the autonomic nervous system creates a milieu for histamine to begin acting on its own without solicitation from the arousal and adaptation cycle.
If histamine levels are elevated in this way, histamine will begin to prolong alpha-states in a way that increases the release of adrenaline. Adrenaline release will be delayed too and also exaggerated in terms of the severity of the adrenal response. This creates and perpetuates the problem of being “out of sync” with environmental cues about time (sunrise, sunset, moon phases, seasons, etc.) and also social cues (that would normally promote a rejuvenative and restorative rest-and-digest parasympathetic state). At this stage in the development of fibromyalgia, histamine acts to produce pain that sometimes feels like it’s in the body, sometimes like it’s floating over the body.
Histamine is produced in the stomach by enterochromaffin cells and as the body starts to heal from fibromyalgia, some patients notice that their internal organs, specifically the stomach, is upset and somehow involved in producing the pain.
Like fibromyalgia and chronic fatigue syndrome, allergies are driven by elevated and unhinged histamine release that’s no longer hooked into the trajectory of the human arousal and adaptation cycle. To overcome fibromyalgia and chronic fatigue syndrome, you’ll have to release your trauma using the sacred indigenous medicines. This can be a long process (it usually takes 1-2 years depending on the patient profile) to produce a permanent cure for fibromyalgia and chronic fatigue syndrome. Patients experience landmarks of progress as they work toward the permanent goal with emotional relief happening first, followed by a slow but steady “retethering” of histamine to the arousal sequence to the adrenal and serotonergic response again.
To learn more about how to work with the sacred medicines to overcome MCAS, set up a health coaching session with us here.
Also, click here to learn more about nicotine patches and amanita muscaria, both of which work very well to naturally cure fibromyalgia, particularly when the patient also works to release trauma as a part of the protocol.
The frustrating thing about MCAS is that it is experienced as a physical disease, but it often begins as a result of an emotional trauma. To retether the histamine response back into the arousal sequence properly, you have to work with mind-body medicines like Ayahuasca, psilocybin, or San Pedro. Working with the sacred medicines can provide a permanent cure for MCAS, but it takes work and persistence. To learn more about how to work with the sacred medicines to overcome MCAS, set up a health coaching session with us here.
Many people use the DreamLight.app in tandem with Eye Movement Desensitization and Reprocessing / EMDR, another at-home trauma-release tool. EMDR and the DreamLight.app are not nearly as powerful as psilocybin or Ayahuasca for trauma-release, but many people begin their journey by working with these tools. Craniosacral therapy can also be extremely valuable as a tool to release deep trauma that's resistant to the DreamLight.app or EMDR.
Resources:
• Gomez-Arguelles, J. M. et al. (2022). Improvement of digestive symptoms of fibromyalgia patients following a diet modification according to histamine release test - an observational study. Retrieved February 19, 2025 from https://pmc.ncbi.nlm.nih.gov/articles/PMC9301665/
• Elixir Compounding Pharmacy (2020). Fibromyalgia and Histamine Intolerance. Retrieved February 19, 2025 from https://www.elixircompounding.com.au/post/fibromyalgia-and-histamine-intolerance?srsltid=AfmBOor3-bet4AVRBg-IPyZ9SAfzz7I8ljKp7cT4q-O7uFTkGMQ2v3Wb
• Clayton, P. et al. (2021). Palmitoylethanolamide: A Natural Compound for Health Management. Retrieved February 20, 2025 from https://pmc.ncbi.nlm.nih.gov/articles/PMC8157570/
• Haas, H. & Panula, P. (2003). The role of histamine and the tuberomamillary nucleus in the nervous system. Retrieved February 19, 2025 from https://www.nature.com/articles/nrn1034
• GIlfillan, A. M. and Tkaczyk, C. (2006). Integrated signalling pathways for mast-cell activation. Retrieved February 21, 2025 from https://pubmed.ncbi.nlm.nih.gov/16470226/
• Urb, M. & Sheppard, D. C. (2012). The Role of Mast Cells in the Defence against Pathogens. Retrieved February 21, 2025 from https://pmc.ncbi.nlm.nih.gov/articles/PMC3343118/#:~:text=Mast%20cells%20are%20found%20in,in%20the%20fight%20against%20pathogens.
• Fede, C. et al. (2023). Detection of Mast Cells in Human Superficial Fascia. Retrieved February 21, 2025 from https://pubmed.ncbi.nlm.nih.gov/37511360/
• Knol, E. F. (2011). Basophil Granulocyte. Retrieved February 21, 2025 from https://www.sciencedirect.com/topics/immunology-and-microbiology/basophil-granulocyte
• Piliponsky, A. M. et al .(2001). Human eosinophils induce histamine release from antigen-activated rat peritoneal mast cells: A possible role for mast cells in late-phase allergic reactions. Retrieved February 21, 2025 from https://www.jacionline.org/article/S0091-6749(01)21163-4/pdf
• Sanyal, R. K. (1960). Histamine Sensitivity in Children after Pertussis Infection. Retrieved February 21, 2025 from https://www.nature.com/articles/185537b0
• Fabris, N. et al. (1986). Thyroid function modulates thymic endocrine activity. Retrieved February 21, 2025 from https://pubmed.ncbi.nlm.nih.gov/3944232/
• Shan, L. et al. (2021). The tuberomamillary nucleus in neuropsychiatric disorders. Retrieved February 21, 2025 from https://pubmed.ncbi.nlm.nih.gov/34225943/
• Shan, L. and Swaab, D. F. (2022). Changes in Histaminergic System in Neuropsychiatric Disorders and the Potential Treatment Consequences. Retrieved February 21, 2025 from https://pubmed.ncbi.nlm.nih.gov/34521328/
• Scammell, T. E. et al. (2019). Histamine: neural circuits and new medications. Retrieved February 24, 2025 from https://pmc.ncbi.nlm.nih.gov/articles/PMC6335869/#:~:text=Thus%2C%20drugs%20that%20interfere%20with%20H3%20receptor,norepinephrine%2C%20dopamine%2C%20and%20possibly%20other%20neurotransmitters%20[11].
• Malmberg-Aiello, P. et al. (2000). Antiamnesic effect of metoprine and of selective histamine H(1) receptor agonists in a modified mouse passive avoidance test. Retrieved February 24, 2025 from https://pubmed.ncbi.nlm.nih.gov/10869801/
• HealthRising (n.d.). Piracetam for Chronic Fatigue Syndrome and Fibromyalgia. Retrieved February 24, 2025 from https://www.healthrising.org/treating-chronic-fatigue-syndrome/drugs/piracetam/
BEFORE YOU READ THIS ARTICLE...
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What causes pain? How Histamine Plays a Role…
In this discussion, we’re going to talk about the role that histamine plays in the perpetuation of chronic pain in situations that were originally set off by trauma or a period of chronic, ongoing stress. Histamine is a hormone that works with our boundaries, both emotional and physical. It is a neurohormone that specifically deals with our ability to identify Self and Non-Self. When a person does not feel “safe” in their environment or if that person is not able to create a boundary around themselves to achieve a fully relaxed state on a reliable basis, histamine-related pain or health issues can become a problem.
That being said, humans are a special type of animal. Even when an environment is technically “safe”, our minds and bodies can serve up looping “trauma reels” that play unconsciously. These “trauma reels” that can make us feel unsafe even though we are, indeed, perfectly safe. In other words, trauma from the past that is not properly released can cause the feelings of being traumatized in the present.
In humans, histamine can be released not only in response to actual danger-issues, but also in response to unconscious or perceived danger-issues.
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Chronic Stress, Trauma, the Immune System, and Pain
A number of chronic pain disorders originate from the problem of an over-solicitation of the fight-or-flight system of the body (also known as the Sympathetic Nervous System). When a person (a child or an adult) is under chronic, ongoing stress, or if that person experiences a sudden traumatic experience, the sympathetic nervous system (the fight-of-flight system) can end up in a state of near-constant activation. During states of sympathetic nervous system activation, patients feel pain. Sometimes the pain feels like it’s inside the body and the tissues, sometimes it feels as though it “floats above the skin” in the energy field overlying the actual material body. This state of near-constant activation is punctuated by periods of a parasympathetic “freeze” or “play dead” response that involves extreme lethargy or brain fog and other symptoms associated with chronic fatigue syndrome.The Sympathetic Nervous System in Rheumatic or Fibromyalgia-Type Pain and Chronic Fatigue Syndrome
The sympathetic nervous system is just one branch of the Autonomic Nervous System (ANS). The ANS is a part of the central nervous system that deals with unconscious control over organs, circulation, and all aspects of our bodily function that we don’t consciously regulate. The ANS is made up of four branches:
- Sympathetic Nervous System Branches
- Alpha-Sympathetic - awake and aware, but in a state of relative relaxation.
- Beta-Sympathetic - fight-or-flight
- Parasympathetic Nervous System Branches
- Dorsal Parasympathetic - “freeze” responses involving lethargy and brain fog
- Ventral Parasympathetic - rest-and-digest states of rejuvenation
Conventional medicine only recognizes two branches of the ANS: the sympathetic nervous system and the parasympathetic nervous system. As such, conventional medicine literally does not have a workable model of the nervous system that would make it possible to heal chronic pain syndromes like fibromyalgia, rheumatism, or chronic fatigue syndrome. The two branches of the sympathetic nervous system that we discuss here are part of a model of medicine known as “endobiogeny”. The two branches of the parasympathetic nervous system that we discuss here are part of a model set forth by Dr. Stephen Porges to describe “play dead” or “freeze” states that involve symptoms such as exhaustion, fever, brain fog, upset stomach, achiness or pain, depression, and other low-energy feelings of being “drained”.
Our bodies are designed to do rest-and-digest in order to repair and rejuvenate in order to prevent wear-and-tear on our organs and tissues, but if a person has experienced chronic, long-term stress or a major traumatic event (or multiple traumatic events that are never released and integrated using trauma-informed therapies or the sacred medicines), the rest-and-digest function that’s controlled by the ventral parasympathetic branch can get hijacked. When this happens, histamine release is increased. When histamine release is increased to pathological levels, histamine begins to act on its own instead of acting in concert with the four branches of the ANS.
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Histamine
Histamine is not always bad. In fact, histamine does a lot of good things in the body:- Histamine is a signaling molecule that’s found naturally in plants and animals.
- Histamine regulates:
- Digestion
- Sexual function
- Sleep
- Blood pressure
- Neurotransmission
- Histamine balances our adaptation and arousal response to stressful stimuli.
Trauma is something that, when triggered, will make use feel as we did in a traumatic moment from the past. These trauma-based feelings involve a shift in histamine where histamine is no longer chronologically synchronized with our normal adaptation and arousal response system (which involves adrenaline and serotonin as important players). Trauma, essentially, causes the body (specifically, the autonomic nervous system and the endocrine system), to become de-synchronized. We experience the past in the present tense as feelings that are identical to feelings that we felt in the past except they’re “stuck”. They lack the natural “arc” of a healthy present-tense emotion.
Histamine, normally functions in the body to synchronize different levels of arousal. In one moment, we might be startled by a loud noise. The body might go into an alpha-sympathetic state of pre-fight-or-flight. In this alpha-sympathetic state, we tune into the environment to check for additional signs of danger. A normal, healthy, non-traumatized person might hear the loud noise and tune in for a few minutes and then return to a state of rest-and-digest (ventral parasympathetic) to continue with what they were doing. But a person who has trauma in their body might go straight from a dorsal parasympathetic state of “freeze” or “play dead” to a beta-sympathetic fight-or-flight state. This happens when histamine is not tethering the adrenaline response to serotonin anymore. A person who has an untethered histamine response will become hyper-reactive to the environment.
Essentially, when histamine levels are too high and not properly tethered into the arousal sequence, the person’s body will stop being able to recognize Non-Self and begin attack Self. This may begin as an emotional issue. It can sound like judgmental or toxic thoughts and mental chatter that’s hard to control sometimes. But it can also turn into issues like cancer, diabetes, chronic pain, autoimmunity, dementia, psychosis, severe mood problems and mental illness, and any chronic, long-term disease state that involves degeneration or nervous system malfunction.
Histamine is an autocoid (as sometimes referred to as a “paracrine” in some models) that’s created from the amino acid histidine. This means that histamine works locally as a hormone in the body. Its effects are supposed to be transient and local (meaning that it typically impacts just one region of the body), but when the sympathetic nervous system is in a state of chronic activation or exaggerated expression, histamine can be overexpressed in an ongoing, abnormal way that, in turn, causes the normal adaptation and arousal cycle to become pathological in terms of exaggerated and delayed responses. In other words, the body begins to over-react as a result of the constant presence of histamine and the timing of histamine release can become disrupted by chronic stress or trauma that isn’t properly released and integrated. Histamine receptor production is upregulated by chronic stress and trauma such that histamine becomes too powerful in the body. It can stop acting locally when provoked and begin having a broader sphere of influence inside the body, a situation that looks like Mast Cell Activation Syndrome, rheumatism, arthritis, fibromyalgia, chronic fatigue syndrome, Post Traumatic Stress Disorder, mental illness, allergies, and more.
But histamine itself is not intelligent, per se. Indeed, a more apt focal point might be the cells that produce histamine. The following cells produce histamine in the human body:
- Mast Cells - These are a type of white blood cell that’s found in connective tissues throughout the body. Mast cells are found in relatively small numbers in the connective tissues under normal circumstances. Mast cells can migrate to different locations in the body, as needed and then mature and receive information from T-cells about antigens found on invading pathogens.
- Basophils - These are another type of white blood cell that’s less common than mast cells. In contrast to mast cells, basophils are found in blood. Like mast cells, they can also rapidly migrate to areas of the body where they’re needed. An influx of basophils is usually accompanied by a simultaneous influx of Th2 lymphocytes and eosinophilic granulocytes. Basophils often show up too late to address allergens directly – they tend to arrive several hours after allergen exposure, and many scientists believe that by the time basophils arrive, allergens have cleared.
- Eosinophils - Eosinophils interact with mast cells in the late stages of an allergic reaction.
- Enterochromaffin-like Cells - Enterochromaffin-like cells in the stomach produce histamine which, in turn, stimulates the release of gastric acids for the digestion of food.
- Neurons - Certain neurons in the central nervous system and digestive tract produce histamine.
- Platelets - Platelets can produce histamine in small amounts.
While histamine often becomes a focal point for patients who are trying to get rid of fibromyalgia, rheumatic disease, severe allergies, and other health issues, in fact, histamine is not “intelligent” per se. It is, however, a visible manifestation of a particular response in the body by intelligent cells. It should be noted, however, that while the immune system might seem intelligent, as a system, it is largely government by other endocrine glands. It doesn’t tend to operate intelligently without receiving orders from the endocrine system, especially the corticotropic axis (the endocrine axis that produces steroids that reduce inflammation, for example) and the thyrotropic axis (the endocrine axis that includes the thyroid gland and the thymus gland).
All of this may seem hopelessly complicated for anyone who is not an immunologist and indeed, it is complicated if we focus exclusively on histamine without considering the macroscopic aspects of the human body. Histamine has become a focal point in the treatment of allergies and other health issues because of antihistamines as drugs. The word “antihistamine” entered the common vernacular in the English language more than 70 years ago with the development of diphenhydramine / Benadryl. By the 1950s there were over 20 antihistamine drugs being marketed. So people are familiar with “histamine” as a potentially problematic thing for which antihistamines can be useful. But histamines are merely a thing that’s produced and then released by higher-level cells such as mast cells or platelets.
Antihistamines: Safety and Effectiveness at Reducing Histamine Levels
There isn’t a great deal of research into antihistamine safety and effectiveness. Most of the studies into antihistamine drugs are short-term and most of them use a very small sample size and they make broad-sweeping general assumptions. There are no studies showing how antihistamines impact people with long-term histamine-related issues such as allergies who take antihistamine drugs for a long period of time. No studies exist to compare the effectiveness of the various antihistamine drugs that are currently on the market.
First generation antihistamines are also anticholinergic medications. Studies have shown that the anticholinergic effects are associated with a heightened risk of dementia and cognitive decline in older patients.
Iodine Deficiency and Pain Disorders
For many people who have chronic pain due to arthritis, fibromyalgia, chronic fatigue syndrome, or any number of disease states involving inflammation, iodine deficiency is a major problem that contributes to chronic pain. In the modern world, iodine deficiency almost never exists in vacuum – it is typically accompanied by bromide and fluoride toxicity as these two substances masquerade in the body as iodine and hijack the thyroid gland and in turn, the thymus gland. Often people experience a significant boost in energy and also improved pain control after they get through the detoxification from toxic halide exposure after regular supplementation with Lugol’s iodine 2% for 30-60 days.The thymus gland is essential in proper immune function. Indeed, the thymus gland is one of just a few essential organs / glands of the immune system. B lymphocytes that originate in the bone marrow (“B” for Bone) migrate to the thymus gland to go through “military training” in this gland that’s located behind the sternum to become T lymphocytes (“T” for Thymus). The B lymphocytes that make the cut (not all of them do) are rewarded with T cell status. T cells that make it through the training process in the thymus gland are then able to police the body looking for pathogens. When they find a pathogen, their job is to grab an antigen off that pathogen that they can then present to a mast cell. Mast cells then choose from an arsenal of weapons and tools to decide how to respond to the threat. Histamine is one of the tools that mast cells can use to overcome a pathogen invasion.
The thymus gland is like a military base in the body where T lymphocytes are vetted and trained from a pool of elite B lymphocytes fresh from the bone marrow. Humoral factors produced in the thymus gland are essential for the maturation and development of T lymphocytes, which act as “soldiers” that stand sentinel against invading pathogens. But the humoral factors that play such an important role in thymus gland activity are regulated by thyroid hormones. For example, if the thyroid gland is hyperfunctioning (hyperthyroid), the thymic humoral factor known as “thymulin” will be too high. If the thyroid gland is hypofunctioning (hypothyroid), then thymulin levels will be too low.
Histamine as an Endocrine Regulator
The tuberomamillary nucleus (TMN) is an area of the hypothalamus where histamine neurons produce histamine. Histamine in this area is catalyzed by the enzyme histidine decarboxylase which deconstructs the amino acid histidine into histamine. On the other hand, histamine is deactivated into an inactive form (tele-methylhistamine / t-MeHA) by the enzyme N-methyltransferase.All histamine receptor types are G-protein coupled. The histamininergic system involves four histamine receptor types, H1 to H4.
The histaminergic system controls the following physiological functions:
- Sleep-wake cycles
- Energy homeostasis
- Endocrine homeostasis
- Sensory functions
- Motor functions
- Cognitive functions
- Learning
- Attention
- Memory
Dysfunction of the histaminergic system can contribute to the following disorders including:
- Alzheimer’s disease
- Parkinson’s disease
- Narcolepsy
- Schizophrenia
- Tourette syndrome
- Autism / ASD
- Depression
- Insomnia
Normally, histamine is produced when a person switches to alpha-sympathetic activation from ventral parasympathetic activation. Serotonin is an autocoid that prolongs ventral parasympathetic activation. Serotonin, in a sense, opposes the action of histamine as a promoter of the alpha-sympathetic activation state. Histamine is released at the very beginning of the activation of an alpha-symapthetic state to prolong alpha-sympathetic activation. So while serotonin promotes and prolongs a rest-and-digest state, in order to prevent over-reactivity of the human organism, histamine is a substance that’s released to maintain alpha-sympathetic activation and prevent, up to a point, the activation of a beta-sympathetic response / fight-or-flight. Another way to look at this idea is to say that histamine is released in an effort to prevent “over-reaction” of the physical body to a perceived threat. But once an over-reaction occurs, if that over-reaction is stimulated by additional trauma or by prolonged and chronic stress, histamine becomes “unhinged” from the triggers such that it becomes an instigator of endocrine system imbalance rather than the agent that keeps the symphony of hormones that deal with adaptation and arousal, in tune and synced up.
Unfortunately, when histamine receptors are increased to a point of critical mass in one or more areas of the body, histamine begins acting as an autonomous hormone that can activate alpha-sympathetic states when they’re not appropriate or needed.
The important takeaway here about histamine, in the context of trauma or exposure to chronic stress, is that this neurohormone acts to produce not only physical symptoms of distress (chronic pain, symptoms of allergy, and autoimmune disease), but also symptoms of psychological and emotional distress (dementia, psychosis, depression, ASD, and more). So while it’s true that histamine is not “intelligent” as a neurohormone. Histamine acts more like a very flexible “hinge” or “pivot” that keeps the endocrine hormones tethered together and working in harmonious unison.
If histamine is disrupted though, this neurohormone seems to act as the instigator of endocrine anarchy. Any number of physical or psychological disorders can develop when histamine is “unhinged”. Once histamine is untethered from the adaptation-arousal cycle and endocrine balance occurs, increasing or reducing histamine levels won’t help. What matters is the rhythm and duration of histamine release, not the amount of histamine in the body. To reduce histamine levels can actually cause endocrine imbalances too. To increase histamine levels creates a similar set of issues.
In order to restore order in the body, we have to look at the endocrine system and the autonomic nervous system in an entirely different way.
Click here to learn more about the DreamLight.app, a guided meditation and brain-entrainment tool.
Histamine Intolerance and Fibromyalgia and Chronic Fatigue Syndrome
“Histamine intolerance” is the buzz phrase used to describe the problem of having histamine that’s gone rogue and that’s no longer coordinated into a normal, controlled “reactionary moment” in the human experience. In other words, if you’ve experienced prolonged stress or a major trauma (or many major traumas) in your life, you might be experience flight-or-flight / beta-sympathetic states too often. These fight-or-flight feelings might not be synced up with your actual experience in the present moment. You might, for example, have anxiety or panic for no reason that you can readily identify. Your body may go from a resting state quickly into a fight-or-flight state and your histamine levels might be untethered from the symphony of other hormones that normally work in concert with it. In psychology, this is called Post Traumatic Stress Disorder (PTSD), but you don’t have to paste this label to your forehead. To simply say that you have trauma that has not been properly released yet is an acceptable way of putting the experience of being out-of-sync with the present moment into words.Pain disorders like rheumatism, fibromyalgia, and chronic fatigue syndrome seem to have no biological origin in part because they are rooted in trauma and derived from the body’s normal trauma response. Trauma and trauma-informed therapies are a field that deals with the mind-body connection, namely the autonomic nervous system and the endocrine system. While trauma-informed therapists rarely discuss things like an exaggerated histamine response with their clients, in fact, histamine “intolerance” (a misnomer) is something that becomes a focal point when clients get to the end of trauma-release therapy using sacred indigenous medicines like psilocybin, Ayahuasca, or Iboga.
In order to understand the histamine response, we have to step away from mainstream science and look at histamine from a totally different perspective. What if, as humans, we have the ability to feel other people using our bodies and not our narrative, logical minds? What if we are energetically connected to other people in a way that can cause us to energetically respond or react to them?
And what if we have the ability, as humans, to send our consciousness to other “realms” that are only tenuously connected to the present tense? What if PTSD and trauma-related dissociation is actually like breaking energy away from the consciousness of the human organism to leave it in a past-tense moment of trauma or to send it into future-tense planning projects in an effort to escape from the mess of the present moment? For example, let’s say that a young adult person is in a serious car accident that’s traumatic. Let’s imagine that this person was on their way to a birthday party. Though this trauma could be released using a variety of techniques, we are no longer schooled in these methods in modern society and we don’t use them. The trauma of experiencing this car accident, thus causes the person to leave a part of their energy, their consciousness in the past where it re-lives the accident over and over again. This person experiences flashbacks or emotional “vortices” of the fear they felt during the accident every time they are exposed to birthdays, birthday party supplies, or anything birthday related that they might see online or on TV.
This hypothetical person would be triggered often by birthday-related material because birthdays are common and birthday supplies are seen in a number of contexts. So this person develops a phobia about birthdays and birthday parties. To cope with it, this person might avoid all of the big box stores or any location where birthday supplies are sold. The person might also develop a generalized anxiety disorder or even depression or psychosis. Physical symptoms of disease might develop, in part, to help this person notice that their body is suffering. This person might develop an autoimmune disease that creates a type of incapacitation that makes it easier for the person to avoid birthday-related material.
This is an over-simplified hypothetical situation, but it depicts how we try to cope with trauma when trauma isn’t properly released within a timely manner. Click here to read more about a real-life scenario involving trauma and how the triggers and unconscious material was portrayed in everyday, conscious life.
Click here to do a free trial of EMDR online.
Overcome Fibromyalgia Naturally by Targeting the Histaminergic System
Scientists have demonstrated already that there’s a direct connection between fibromyalgia and overactive mast cells. But in a lot of the content online about fibromyalgia and overactive mast cells, the mast cells are cast as the problematic focus driving the chronic pain. While mast cells are, in fact, one type of cell that produces and releases histamine, leukocytes, and enterochromaffin cells in the stomach also release histamine. And an elevated histamine release is caused, in the initial stages of fibromyalgia development, by chronic, ongoing alpha-sympathetic states. In other words, elevated histamine release is caused by chronic, ongoing stress, or by the buildup of moderate or major traumatic experiences that have not been released by the body.
In a normal, healthy cycle of arousal and adaptation, we begin in a rest-and-digest state. This state is supported and prolonged by the release of serotonin in the gut and in the brain. If something happens in our environment, we launch into an alpha-sympathetic state which is supported and prolonged by histamine. If this level of arousal is elevated to fight-or-flight (beta-sympathetic), histamine, at normal levels in the body will help to return the body back to a brief state of first, dorsal parasympathetic “freeze” response, and then into a state of ventral parasympathetic rest-and-digest.
When a person has been chronically stressed or even chronically triggered in terms of their traumas from the past, the alpha-sympathetic state gets prolonged and histamine levels are elevated as a result. For a while, histamine remains dependent on adrenaline and other hormones that spur the alpha-sympathetic state to calm down, but over time, if the pattern of prolonged alpha-sympathetic continues, human tissues begin to produce more and more histamine receptors. In other words, the body listens to the urgency of the demand that’s being produced by stress or trauma. The body or, in other words, the autonomic nervous system creates a milieu for histamine to begin acting on its own without solicitation from the arousal and adaptation cycle.
If histamine levels are elevated in this way, histamine will begin to prolong alpha-states in a way that increases the release of adrenaline. Adrenaline release will be delayed too and also exaggerated in terms of the severity of the adrenal response. This creates and perpetuates the problem of being “out of sync” with environmental cues about time (sunrise, sunset, moon phases, seasons, etc.) and also social cues (that would normally promote a rejuvenative and restorative rest-and-digest parasympathetic state). At this stage in the development of fibromyalgia, histamine acts to produce pain that sometimes feels like it’s in the body, sometimes like it’s floating over the body.
Histamine is produced in the stomach by enterochromaffin cells and as the body starts to heal from fibromyalgia, some patients notice that their internal organs, specifically the stomach, is upset and somehow involved in producing the pain.
Like fibromyalgia and chronic fatigue syndrome, allergies are driven by elevated and unhinged histamine release that’s no longer hooked into the trajectory of the human arousal and adaptation cycle. To overcome fibromyalgia and chronic fatigue syndrome, you’ll have to release your trauma using the sacred indigenous medicines. This can be a long process (it usually takes 1-2 years depending on the patient profile) to produce a permanent cure for fibromyalgia and chronic fatigue syndrome. Patients experience landmarks of progress as they work toward the permanent goal with emotional relief happening first, followed by a slow but steady “retethering” of histamine to the arousal sequence to the adrenal and serotonergic response again.
To learn more about how to work with the sacred medicines to overcome MCAS, set up a health coaching session with us here.
Also, click here to learn more about nicotine patches and amanita muscaria, both of which work very well to naturally cure fibromyalgia, particularly when the patient also works to release trauma as a part of the protocol.
How to Cure Mast Cell Activation Syndrome (MCAS) via Histamine Tethering
In Mast Cell Activation Syndrome (MCAS), people often experience postural orthostatic tachycardia syndrome (POTS) when their body fails to time the shift from a parasympathetic rest-and-digest state (a seated position) to an alpha-symapthetic state that’s more active (standing). As we discussed above, histamine tethers one state of arousal to another to make a smooth adjustment from rest-and-digest (or “freeze” / “play dead”) to “fight-or-flight”, etc. Flushing and shortness of breath is an alpha-sympathetic or a beta-sympathetic phenomena. Symptoms such as headaches, skin rashes, excessive urination, light-headedness, gastrointestinal symptoms, and even vomiting can all be traced back to this overzealous arousal response that’s normally tightly regulated and kept balanced by histamine.The frustrating thing about MCAS is that it is experienced as a physical disease, but it often begins as a result of an emotional trauma. To retether the histamine response back into the arousal sequence properly, you have to work with mind-body medicines like Ayahuasca, psilocybin, or San Pedro. Working with the sacred medicines can provide a permanent cure for MCAS, but it takes work and persistence. To learn more about how to work with the sacred medicines to overcome MCAS, set up a health coaching session with us here.
Summary
If you aren't ready to work with the sacred medicines to release trauma in order to cure fibromyalgia, chronic fatigue, chronic pain syndromes, or MCAS, start by working with the DreamLight.app, a brain entrainment and guided meditation tool as an alternative that gives you the power to release trauma using at-home treatments.
Click here to learn more about the DreamLight.app, a guided meditation and brain-entrainment tool.
Many people use the DreamLight.app in tandem with Eye Movement Desensitization and Reprocessing / EMDR, another at-home trauma-release tool. EMDR and the DreamLight.app are not nearly as powerful as psilocybin or Ayahuasca for trauma-release, but many people begin their journey by working with these tools. Craniosacral therapy can also be extremely valuable as a tool to release deep trauma that's resistant to the DreamLight.app or EMDR.
Click here to do a free trial of EMDR online.
Resources:
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• Clayton, P. et al. (2021). Palmitoylethanolamide: A Natural Compound for Health Management. Retrieved February 20, 2025 from https://pmc.ncbi.nlm.nih.gov/articles/PMC8157570/
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• Malmberg-Aiello, P. et al. (2000). Antiamnesic effect of metoprine and of selective histamine H(1) receptor agonists in a modified mouse passive avoidance test. Retrieved February 24, 2025 from https://pubmed.ncbi.nlm.nih.gov/10869801/
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