You’re probably wondering “what’s the deal with high dopamine AND histamine?”

Well, let’s just say dopamine and histamine actually have a love-hate relationship going on. Let me explain… let’s imagine that dopamine is a chameleon and histamine is a fly.
The chameleon is a super chill kinda guy, always in a good mood, carefully specs things out and strategically plans his game in order to successfully catch his meal and is always great at blending in and just enjoying life; Whereas the fly is a super hyper, very obvious, annoying, strung tight, twitchy and an all over the place kinda guy. But even though Mr. Fly is such a pest, Mr. Chameleon still needs his dinner and without Mr. Fly there would be no Mr. Chameleon… and without Mr. Chameleon there would be too much of Mr. Fly.

So the moral of the story is, both dopamine and histamine are needed and have a lot in common and I’ll elaborate on that in just a minute.

But unlike the chameleon and the fly, histamine and dopamine actually have very similar traits, however, there are some small distinctive differences. This is one of the biggest reasons why a lot of people could think they have high dopamine, when in fact, they actually just have high histamine.

The basics about histamine and dopamine

Histamine is created from histidine, by the enzyme histidine decarboxylase (HDC), and is deactivated by catechol-O-methyltransferase (COMT; methylation cycle), histamine methyltransferase (HNMT) and monoamine oxidase B (MAO-B; the same enzyme that breaks dopamine down) (R).

Histamine binds to 4 known receptors, namely H1 to H4. H3 is the auto-receptor and activating it lowers histamine, as well as dopamine, GABA, noradrenaline and acetylcholine (R).

Dopamine is created from the amino acids phenylalanine and tyrosine. Phenylalanine → tyrosine → L-Dopa → dopamine.

Dopamine binds to 5 known receptors, namely D1 to D5. D2 is its autoreceptor and activating it lowers dopamine levels. Dopamine is then broken down by MAO-B and COMT.

Let’s get to the good stuff.

〉 Dopamine & histamine on motivation & drive

Both dopamine and histamine are involved in promoting drive, goal-orientation, desire for something, creativity, motivation and the energy for execution.

However, the difference between the two is that histamine, when in excess, leads to hyperactivity, OCD, perfectionism and even irritation and aggression; more like the type A personality.

Usually, when histamine is high, dopamine is low and antagonizing the H3 auto-receptor increases dopamine.

Excess histamine also promotes addiction. Its been found that when histamine is highest, chances for addiction or relapse is the highest. Estrogen and cortisol is also heavily involved as both increase histamine, all of which promote addiction (R). During periods of stress, and/or excess estrogen, chances of addiction or relapse is the greatest.

Addiction has always been thought to be driven by dopamine, but it’s been found that it’s dopamine hypo-activity that leads to addiction. People with addiction usually have low dopamine or less D2 receptors, thus they require more dopamine releasing substances just to feel “normal” again. A lack of dopamine and/or an excess of serotonin (serotonin also suppresses dopamine release (R)) causes anhedonia; the lack of pleasure.

> The high serotonin personality

Excess glutamate is also involved in addiction and postsynaptic D2 receptor activation suppresses glutamatergic transmission through endocannabinoid signaling, whereas presynaptic D2 receptor activation suppresses glutamatergic transmission through endocannabinoid independent signalling.

As dopamine drops, due to chronic stress or serotonin, less D2 is activated and this may lead to elevated glutamatergic signalling which may contribute to addiction (R). Additionally, low striatal D1 receptor availability leads to more risk-seeking behavior, a character trait known to be associated with an increased risk of addiction (R). Again, low dopamine and/or dopamine receptors lead to addiction.

Plus, dopamine is involved in desire and wanting, but not so much in the liking/rush/relief (which is more opioids and oxytocin driven (R)). Meaning, dopamine might cause you to crave something or to pursue something, but once you get it, you only get a minor boost in dopamine and not a major rush.

Unexpected rewards, which are greater than expected ones, do cause a surge in dopamine, but not familiar rewards (R). This is also why some people are addicted to partying, firstly because alcohol and other recreational drugs increase dopamine temporarily, but also the fact that most things are random at parties. Nothing really happens according to a set plan, which often leads to unexpected “reward” which then results in temporary bursts of dopamine. Once again, this type of addiction is due to low dopamine and any type of addiction diminishes dopamine levels even more.

Restoring normal dopamine levels and receptor sensitivity will reduce addictive behavior.

“…hypo-dopaminergic function and result in abnormal craving behavior. To activate their dopaminergic pathways, a self-healing process to offset their low D2 receptors, individuals are driven to engage in activities which will increase brain dopamine function (Noble et al., 1991, 1993; Delis et al., 2013). The consumption of alcohol in large quantities or carbohydrate binging stimulates the brain’s production of and utilization of dopamine (Blum et al., 1996, 2000). So too does the intake of crack cocaine, cocaine, opioids, and the abuse of nicotine. Aggressive behavior has also been associated with this genetic abnormality which also stimulates the brain’s use of Dopamine. Low dopamine also leads to addictive, compulsive and impulsive behaviors.” (R)

As a side note, excess serotonin, with low dopamine, contributes to impulsivity. (R)

Low histamine and dopamine leads to excess fatigue during the day, slow mental function, hypo-activity (not very active during the day), constant munchies, anxiety, etc. Antagonizing the H3 receptor increases histamine and dopamine, which as a result improves energy during the day, sleep at night and also boosts mental function and reduces appetite.

〉 Dopamine & Histamine on Learning & Focus

Both histamine and dopamine (and oxytocin; by releasing dopamine) promote exploration, learning, focus and habit formation. In an adverse event, both histamine and dopamine ingrain the “successful strategy” that resolved the stressor. However, chronic stress could lead to excess dopamine in the short term, but in the long term, the dopamine system will be downregulated which increases the risk of addiction, reduced mood and mental function.

Blocking the NMDA receptor (with magnesium or ketamine) inhibits release of dopamine bursts during stress and is able to prevent the drop in dopamine after the stress has passed (R, R, R).

The difference between histamine and dopamine is that dopamine mostly promotes exploration of things outside the comfort-zone, whereas histamine mostly promotes exploration inside the comfort-zone and makes you prone to forming habits.

Histamine can create more of a rigid, manic personality because of the formation of habits and excess energy. Stress increases histamine (R) and impairs flexible thinking, but improves performance of rehearsed things, which can make you rigid and feel like you’re stuck in a rut or groove (R). It might not even be on purpose that you do certain things, it’s just that you’ve always been doing it and it feels most comfortable to continue doing so. And anything that might disrupt the rigidness makes you feel agitated, uncomfortable and that you just want to avoid it. Unless the goal is to change something purposefully, then the change might be accepted, but change is slow as habits are slowly reformed.

LSD, which is a histamine antagonist (R), promotes creativity when micro-dosed, indicating that histamine might put reins on creativity, and that it’s actually dopamine that’s more involved in creativity (although both is important).

High dopamine promotes a creative, socially comfortable (pro-social, no anxiety), more fluid and flexible personality (R, R). Dopamine is also involved in learning – what to avoid that might put you in danger – but uncomfortable situations might rather be seen as opportunities instead of difficulties.

Low histamine and dopamine (together with excess noradrenaline) might reduce attention span, increase distractions and lead to ADHD and ADD and reduce learning and cognitive function. On the other hand, high histamine (together with acetylcholine) might make you over focused, OCD-like tendencies and perfectionistic. It can make you obsessed with something until you “perfect” it according to your taste.

It’s rather low dopamine (with low acetylcholine) that reduces cognitive function as H3 antagonism, which increases histamine, dopamine and acetylcholine, improves learning and cognitive function (R). Remember, high histamine usually means low dopamine, but high dopamine doesn’t necessarily mean low histamine.

〉 Dopamine & Histamine on Mood

Both dopamine and histamine improve mood and can create a state of euphoria. Low histamine and dopamine causes anxiety (R, R) and low dopamine specifically causes sadness and anhedonia, all of which can promote depression (R, R). Some research indicate that the anti-depressant effect of SSRI drugs depend on the release of histamine, by activating the 5-HT2C receptor (R). A lot of people with elevated histamine struggle with depression (often suicidal), but because histamine is already in excess, there’s a huge chance that the SSRI drugs will only make it worse. Which is also why a lot of people commit suicide even while being on SSRI drugs. Bottom line… increasing histamine isn’t the solution for depression.

Histamine is negatively correlated with apathy, however, too much histamine might make you hyper-emotional as it promotes the release of estrogen and oxytocin (R). An excess of histamine can also lead to aggression by activating H2 (R). Activation of the H2 receptor releases serotonin and acetylcholine and also inhibits the release of GABA.

Excess histamine and low dopamine can cause the “freeze response” (hypervigilance), similar to high serotonin, possibly because histamine promotes the release of serotonin (R, R, R). On the other hand, low histamine and high dopamine can help you stay cool under pressure, improve mental function, creativity, problem solving and avoid freezing, stuttering, etc.

The reason why dopamine and histamine have such overlapping properties is because histamine promotes the release of dopamine and vice versa. 

For example, dopamine, by acting on the D2 receptor is able to release histamine (R). In fact, the wake promoting effect of dopamine requires the release of histamine.

Under more normal, healthy conditions, dopamine and histamine are often inversely correlated. A fast metabolism, fueled by adequate thyroid hormones, increases the sensitivity of histamine to its receptors, which reduces overall histamine levels and boosts dopamine levels. One of the thyroid hormone metabolites, 3-iodothyroacetic acid (TA1), has an anti-depressant effects through brain histamine (R).

Bottom line, both histamine and dopamine are important for wakefulness, creativity, being goal driven, motivated, feeling happy, etc., but ideally dopamine should be high and histamine low. Optimal dopamine levels will ensure proper and adequate histamine signalling. Many of the benefits of dopamine are also due to testosterone, as dopamine has a pre-metabolic and pre-steroidogenic effect.

> The high testosterone personality

So how do we ensure optimal dopamine levels?

You can check out this article on boosting dopamine for a comprehensive list on dopamine boosting strategies and supplements.

> 55 ways to increase dopamine

Some additional signs of high histamine include:

• Insomnia
• Gastric pain
• Nausea
• Persistent headaches & migraines.
• Chronic inflammation; joints, skin, gut, etc.
• Water retention due to aldosterone secretion
• Always hot, good tolerance of cold, but a poor tolerance of heat
• Poor pain tolerance (R)
• High libido (Dopamine also promotes libido. High prolactin and low dopamine abolishes libido)
• Scarce or complete lack of body hair
• Long and slender fingers. Second toe is often longer than big toe
• Lots of saliva, tears and mucus
• Fast metabolism and low body fat. It’s not only histamine that speeds up the metabolism, but also dopamine. Co-activation both D1 and D2 receptor significantly increase protein mass while reducing body fat, body weight, food consumption and serum concentrations of triglycerides, free fatty acid glucose, and insulin (R).

Some additional signs of low histamine include (low histamine is often accompanied with excess copper):

• Heavy growth of body hair
• High body fat percentage 
• Racing thoughts
• Paranoia
• High pain tolerance
• Difficulty orgasming, delayed ejaculation, due to excess serotonin and 5-HT1A desensitization.
• No headaches or allergies
• Dry mouth or eyes

High copper in the brain can cause a state of

• Restlessness
• Insomnia
• Violence
• Depression
• Irritability
• Paranoia
• High Blood Pressure

As always, thanks so much for reading my article.
If you found it helpful and insightful please like and share so others can also benefit from this information and feel free to leave a comment down below if you have any questions for me.

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