Understanding Magnesium's Powerful Effect on Migraines, Anxiety, Sleep, and Mental Health
September 27, 2020
For 30 years.
It would start with a slight twinge in my left hand.
My visual field would then flatten and I knew what I was in for over the next 24 hours (and even week).
Another migraine.
The left hand would then go numb and this numbness would spread through specific areas of my face - mouth, gums, tongue.
Vision would completely go out with a static-like effect and severe tunnel vision. My head would throb and I would have to shut down for 24 hours.
No way around it and this would occur a few times a year for about 30 years.
Until magnesium.
I now take it daily, three times a day and on the off occasion that stress, sleep, or food breakthrough to that twinge in my left hand.
Magnesium is the only thing that can stop it when it's started and I've tried everything.
If I had only known about this earlier!
What on earth is going on there with such a simple and simply dismissed mineral like magnesium?
We'll get into but the ramification are not limited to migraines.
In fact, magnesium is an integral player in the most important and dynamic balance in our brain or nervous system.
The GABA and glutamate dance.
Don't worry, we're going to unwrap this whole process and see how it affects sleep, migraines, seizures, and just about every mental health issues under the sun.
These are the areas we'll cover:
- A quick introduction to magnesium starring roll in the brain
- Why glutamate balance is so important
- The power of GABA to calm down the brain
- Magnesium and stress
- Magnesium and sleep
- Magnesium and migraines
- Magnesium and mental health - anxiety, panic attacks, OCD, and more
- What's the best kind of magnesium (very important!!)
- How much magnesium to take
Let's get started before the twinge comes back.
A quick introduction to magnesium starring roll in the brain
Magnesium is a very common mineral on Earth and as a result, it's prevalent in the inner workings of our own chemistry.
Especially in the nervous system.
It has a very specific function in probably the most fundamental system in our brain.
The excitatory/inhibitory system - the domains of glutamate and GABA.
Glutamate is the "gas" pedal of the brain.
As the most common neurotransmitter, it powers every neuron and every other pathway (serotonin, dopamine, etc.).
GABA is the opposing force and it calms activity both at the neuron level and across the brain.
The two are in a constant dance with delicate controls to keep a healthy balance with occasional and needed wins on either side.
For example, during sleep, GABA needs to win. For your exam, glutamate better be present.
But then...back to balance.
In fact, the brain has a complex system for making sure glutamate is maintained at a healthy but not excessive level.
Why? When glutamate runs "hot", it can fry out neurons.
It's like red-lining your car engine...eventually, the engine will be destroyed.
So...how does magnesium come into play?
By virtue of its chemistry and shape, magnesium is able to fit into the primary glutamate receptor called NMDA.
It essentially blocks glutamate from being active!
Think of it as a buffer against glutamate activity.
Newer research is really pointing to issues with glutamate across a range of mental health issues...maybe all of them in some way or form.
This excess glutamate can come from a range of different causes.
We've covered how the immune system is now front and center in mental health research.
Microglia, our brain's primary immune commander, can release glutamate (along with a host of inflammatory assassins) when hyperactivated.
GABA pathways can be exhausted or impaired (genetics figures in here as does the gut microbiome).
Various drugs can drive glutamate activity (stimulants, etc).
Then there's stress. Chronic stress. We'll look at that below.
Glutamate is essential for proper brain function at the most basic level but it's so caustic when excessive that the brain has multiple hedges.
- GABA is primary in this role.
- Glycine is a secondary protection.
- N-acetyl cysteine acts like a sponge for excess glutamate (see NAC for mental health and addiction)
- Then there's mag.
Magnesium literally blocks glutamate from its receptor and functions as a dampener in its own right.
Let's look at what happens when glutamate runs hot.
Why glutamate balance is so important
Let's first drill down to individual neurons:
In both cases, cells activated by glutamate become overexcited. This overexcitation can lead to effects that can cause cell damage and/or death.
https://hopes.stanford.edu/about-glutamate-toxicity/
So death of neurons. That's bad!
Too much of this for too long and you see actual reduction in brain mass across various areas.
In fact, chronic glutamate hyperactivation is linked to a slew of neurodegenerative diseases and mental illness.
Or it can happen in one mad dash.
Stroke is an example where the brain can experience a glutamate "storm". Traumatic brain injury is another one.
Not enough glutamate is also an issue as brain activity requires it to function at the cellular level.
We'll focus on excess glutamate since so many of our modern ailments point in this direction.
Studies looked at mice who were bred to have excess glutamate and the effects we're profound:
The consequences seem to be highly dependent on the degree of L-glu increase but even a 10% increase appears to affect nerve cell structure and survival particularly in the context of aging suggesting that chronic excitotoxicity may be particularly relevant to age-related neurodegenerative diseases.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679930/
If you think about what having too much excitation in the brain would feel like, many clear repercussions arise.
We're not talking about "feeling energetic"...we we're talking about the nervous system having too much excitation.
Think 5th cup of coffee. That frazzled, coming out of your skin feeling where your nerves are "shot".
Clearly, this would manifest with:
- Insomnia
- Nerve pain (glutamate is now playing a starring role hence the ketamine effects)
- Seizures
- Anxiety
- Migraines
- OCD
- Repetitive thoughts
- Irritability and mood disorders
- ADHD
And on and on.
Even depression can result from chronic excess glutamate.
How, you ask, would an excitatory chemical cause lack of lust or joy?
Again, too much glutamate can damage the prefrontal cortex and parts of the brain that need to function for us to feel engaged (and in control).
Magnesium acts as a safety break if GABA fails or is used up followed by a drop in acetylcysteine (glutamate sponge). It literally fits right into the receptor:
More specifically, magnesium blocks the calcium channel of the N-methyl-D-aspartate (NMDA) glutamate receptor, and thereby regulates calcium entry into the postsynaptic neuron.
https://www.ncbi.nlm.nih.gov/books/NBK209305/
Studies have look at magnesium following stroke (a glutamate storm) to see if it was protective.
The results:
Magnesium Sulfate Protects Against the Bioenergetic Consequences of Chronic Glutamate Receptor Stimulation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827425/
Let's turn our attention to the other side of the equation.
GABA.
The power of GABA to calm down the brain
What keeps glutamate at bay?
GABA.
Interestingly, GABA is made from glutamate and there's a powerful feedback system to keep the two in balance depending on what is needed.
In general, GABA is our calming neurotransmitter both at the cellular level and system-wide.
Just look at the class of drugs that boost GABA.
Benzos like valium, Xanax, and Attivan. The barbituates came before them.
The newer sleep aid follows.
They all, in one way or another, boost GABA function.
Unfortunately, they come with addiction and normalization (see CBD versus benzos for anxiety or CBD and GABA ).
You can't just pump GABA in one direction without the brain panicking and pushing back by reducing sensitivity and even GABA receptor numbers.
It leaves you worse than when you started.
To see how GABA feels, let's follow the trail of increasing benzo effects with increasing dosage:
- Calm
- Sedated
- Hypnotic
- Amnesiac
- Anesthetized
- Dead!
Yes, with a significant enough dosage (usually in conjunction with opioids or other depressants), you'll just stop breathing.
Again, GABA slows down activity.
What else drives GABA?
Just human's drug of choice...alcohol (see CBD and alcohol or why so many woman are drinking as they get older).
The bigger secret is this. Progesterone drives GABA activity and most women have lost 50% of their progesterone by age 40.
No wonder women in their 40's start drinking.
It's self-medicating unless you supplement bioidentical progesterone.
Let's turn now to a primary culprit in today's world.
Magnesium and stress
GABA may be insufficient due to genetics to keep up with glutamate or it might just be eaten up by stress.
Yes, stress.
Many studies have looked at both acute and chronic stress for GABA function and they results are pretty dire:
We observe a depolarizing shift in EGABA in hippocampal CA1 pyramidal neurons after chronic stress.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272449/
The hippocampus is a critical hub of mood control and very vulnerable to stress.
Cortisol, our primary stress hormone, drives glutamate production.
It literally eats up GABA as a result.
This makes sense if you think about it.
Stress is just evolution's way to say...Hey, stop doing that or Hey, you need to do this NOW!
Calm is not the response you want if there's a bus careening towards you!
Unfortunately, the body can't discriminate between an upcoming bus and the stresses of modern life.
It's all cortisol! (See CBD and cortisol ).
Glutamate is the needed neurotransmitter to get things moving to address whatever is causing you the stress!
Too much of it for too long...well, we know how that plays out from above.
Again, insufficient GABA is tied to a range of issues...the same ones as too much glutamate since they're opposing forces in the brain.
Magnesium affects GABA in a roundabout way by reducing the load of glutamate.
Let's start to dig into the various issues most affected by magnesium.
First up...sleep.
Magnesium and sleep
Sleep is the domain of GABA. All the newer sleep aids directly drive GABA (or reduce histamine).
Unfortunately, addiction and tolerance generally follow the GABA boosters.
What about magnesium before bed?
Cut to the chase:
Magnesium supplementation improves sleep efficiency, sleep time and sleep onset latency, early morning awakening, and insomnia objective measures such as the concentration of serum renin, melatonin, and serum cortisol, in older adults
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910806/
Maybe more importantly, it improves deep sleep.
This is where the magic happens in terms of removing toxins and general brain maintenance.
The waste removal process is critical to dementia and other neurological diseases (see CBD and dementia).
What about a trial comparing magnesium supplementation to placebo in the elderly:
As compared to the placebo group, in the experimental group, dietary magnesium supplementation brought about statistically significant increases in sleep time (P = 0.002), sleep efficiency (P = 0.03), concentration of serum renin (P < 0.001), and melatonin (P = 0.007), and also resulted in significant decrease of ISI score (P = 0.006), sleep onset latency (P = 0.02) and serum cortisol concentration (P = 0.008).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703169/
There's a fascinating connection between magnesium and serotonin, a key player in sleep and stress response.
Brain Mg deficiency reduces serotonin levels, and antidepressant drugs have been shown to have the action of raising brain Mg.
https://www.ncbi.nlm.nih.gov/books/NBK507265/
Serotonin is tied to every human behavior, including sleep. Check out CBD and serotonin to dive deeper into this fascinating master regulator.
We'll see the impacts of magnesium and serotonin below with depression.
As for sleep, we have a full review of CBD and sleep which really gets into the role of serotonin.
Let's turn to pain.
Magnesium and migraines and pain
First migraines which is more of a vascular issue than a straight pain issue. See CBD and migraine to really dive into what happens during migraines.
New research is showing that magnesium may be a powerful tool for migraine, especially if accompanied by an aura (visual disturbance).
The theory is that some brains exhaust magnesium which set up a cascade of pain and suffering.
The available evidence suggests that up to 50% of patients during an acute migraine attack have lowered levels of ionized magnesium.
https://pubmed.ncbi.nlm.nih.gov/9523054/
Keep in mind that magnesium is also used in the cardiovascular system to smooth vascular walls.
In fact, magnesium can drop blood pressure.
Back to migraines:
Infusion of magnesium results in a rapid and sustained relief of an acute migraine in such patients. Two double-blind studies suggest that chronic oral magnesium supplementation may also reduce the frequency of migraine headaches.
https://pubmed.ncbi.nlm.nih.gov/9523054/
Let's turn to pain in general...especially nerve pain or neuropathy. Chronic pain.
This may offer a clue:
A major mechanism of pain is the excessive stimulation of a brain chemical called "NMDA."
https://www.psychologytoday.com/us/blog/complementary-medicine/201009/magnesium-pain-relief#
Wait a minute...NMDA sounds familiar from above. What was it again?
The N-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel protein found in nerve cells.
https://en.wikipedia.org/wiki/NMDA_receptor
Goodness...it's the primary glutamate receptor.
Newer research is pointing to excessive glutamate activity at specific pain nerves that burn out the nerve (neuropathy) or leave it "stuck" with "pain on" signaling.
This is the basis behind topical ketamine treatment.
What about magnesium and pain?
Let's put the pieces of the puzzle together:
Magnesium plays an important role in the prevention of central sensitization and in the attenuation of established pain hypersensitivity, and its main mode of action appears to involve its voltage-gated antagonist action at N-methyl-D-aspartate (NMDA) receptors
https://www.ncbi.nlm.nih.gov/books/NBK507245/
To translate, magnesium calms glutamate activity at the pain receptor location.
Remember, glutamate drives the activity of whatever neuron it's stimulating.
If it's a serotonin neuron, more serotonin.
Get this...it can even drive GABA activity by stimulating GABA neurons!
It also acts as a muscle relaxer but the primary research is on nerve pain:
Let's turn our attention to the big (in our opinion anyway). Mental health.
Magnesium and mental health - anxiety, panic attacks, OCD, and more
Magnesium is a big player in the brain so we would expect to see impacts with mental health.
We already went through how GABA/glutamate balance is critical to every working system in the brain.
Let's now get specific.
We'll focus down on just a sampling:
- Magnesium and depression
- Magnesium and anxietyMagnesium and schizophrenia
- Magnesium and OCD
- Magnesium and Panic Attacks
- Magnesium and PTSD
- Magnesium and mood
- Magnesium and seizures
Again, glutamate is everywhere...the most prevalent neurotransmitters in our brain.
Magnesium and depression
We mentioned how glutamate could actually damage brain tissue. The result can manifest as depression, depending on the brain area.
There's long been a known connection between chronic stress and depression and as we know, cortisol and stress hormones boost glutamate.
Our body literally dumps magnesium in the presence of stress:
Acute emotional stress, which involves an activation of the SNS and the HPA axis, led to an increase in Mg excretion in humans
https://www.ncbi.nlm.nih.gov/books/NBK507265/
So, what are studies showing for mag supplementation and depression:
Consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in PHQ-9 scores of -6.0 points (CI -7.9, -4.2; P<0.001) and net improvement in Generalized Anxiety Disorders-7 scores of -4.5 points (CI -6.6, -2.4; P<0.001).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487054/pdf/pone.0180067.pdf
Interestingly, the effects were across the board:
Similar effects were observed regardless of age, gender, baseline severity of depression, baseline magnesium level, or use of antidepressant treatments.
Results were seen in 2 weeks.
This is fascinating because it speaks to another important clue we covered in our CBD and depression review.
Neurogenesis, or the process repairing brains from the ravages of glutamate, stress, immune response, etc, takes about 2 weeks to show.
We know this from studies on SSRI where increase serotonin boosts BDNF, our brain's fertilizer.
People, BDNF is your new best friend for mental health and addiction. See CBD and BDNF or CBD and brain repair.
Essentially, magnesium is calming the damage so that the brain's repair mechanism can catch up.
Researchers are finally teasing this out:
Magnesium significantly increased the levels of BDNF, GluN2B, P-S831, and P-S845 protein (and mRNA) primarily in the PFC and the hippocampus in OB rats.
https://pubmed.ncbi.nlm.nih.gov/25027582/
The Holy Grails - more BDNF (see review of psilocybin as an example).
Anxiety also improved in that study (as well as headaches, muscle cramps, and more).
In another study:
In humans, 12 weeks intake of 450 mg of elemental Mg has been shown to be as effective in reducing depression symptoms as a tricyclic antidepressant (Imipramine 50 mg) in depressed hypomagnesic elderly patients with type II diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452159/
This was for people with low magnesium but that casts a wide net.
Sixty-eight percent of Americans [3] and 72% of middle-aged French adults [6] have been shown to consume less than the recommended levels of dietary Mg.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452159/
So almost 7 in 10 adults in the US. Mineral absorption gets worse as we get older so the above study is very relevant.
Magnesium is absorbed by plants but only when bacteria in the soil can assist.
Pesticides and other chemicals have severely depleted the general quality of mag in our food supply along with many minerals.
Let's look at the anxiety piece. Same process at work here.
Magnesium and anxiety
We did a full review of the mechanisms of anxiety here .
The primary anti-anxiety medications boost GABA, albeit with nasty side effects (addiction and tolerance).
Clearly, GABA/glutamate activity is at work here.
Structurally, we also see where an impaired prefrontal cortex (our rational brain) is unable to keep our more emotional and primitive brain (the amygdala) in check.
The damage can result from all the usual suspects:
- Overactive immune response
- Excess glutamate
- Trauma
- Chronic stress
This allows the amygdala to run wild and fear or anxiety can result.
In animal studies, they can induce anxiety states by reducing magnesium absorption.
There's also a correlation between blood levels of mag and anxiety:
Blood plasma and brain Mg levels are also significantly correlated with anxiety-related behavioral responses in rodents
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452159/
Remember how stress causes magnesium to dump out of our bodies?
The effects here:
Test anxiety, related to exposure to stressful exam conditions, increases urinary Mg excretion, resulting in a partial reduction of Mg levels
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452159/
The net take away is this…
Magnesium is integral to our stress response!
Look at the results:
Magnesium supplementation has also been shown to attenuate the activity of the HPAA, including a reduction in central (ACTH; [15]) and peripheral (cortisol; [49]) endocrine responses of this system.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452159/
Goodness. HPA is our fight or flight system (in addition to others).
ACTH drives adrenaline. Cortisol is our primary stress hormone. See CBD and cortisol.
You can think of anxiety as a threshold crossed in our stress response system. Magnesium is the buffer there (along with serotonin and anandamide).
Check out tryptophan as a buffer for social stress since tryptophan supports serotonin.
At the heart of magnesium for anxiety is its effect on GABA/glutamate balance.
Too much glutamate will exhaust GABA and anxiety is ONE result of this:
The action of glutamate on mGluRs receptors has been implicated in responses to fear, anxiety and panic
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452159/
Mag also increases GABA activity. Again, we've sang it praises for sleep and anxiety for years now (see Dre's list).
Let's turn our sights to more severe issues.
Magnesium and schizophrenia or bipolar
If you read our CBD and schizophrenia review, you'll very familiar with topics.
Inflammation. Stress. Hyperactive immune response. Glutamate!
In fact, these recurring insults occur across the range of mental health but if they're present during critical periods of brain development (in utero, age 2-3, puberty, etc.), it can affect the communication pathways and areas of the brain structurally.
You see this in more severe illnesses like schizophrenia, bipolar, and autism.
What about magnesium?
Changes in plasma and intracellular magnesium concentration, as well as in other bivalent cations, have been found in both psychoses.
https://www.ncbi.nlm.nih.gov/books/NBK507255/
The other being bipolar.
Interestingly, some of the big anti-psychotics raised levels of magnesium as a side hustle (to squashing dopamine levels).
There's a fascinating dance between glutamate and dopamine, the latter being squarely implicated in schizophrenia.
- Too much dopamine in one area (striatum) leads to the "positive" symptoms like delusions, hallucinations, paranoia, etc
- Too little dopamine in another area (prefrontal cortex) leads to the "negative" symptoms like low effect, slow cognition, etc
Here's the key point:
In terms of the glutamatergic hypothesis of schizophrenia that involves the imbalance between glutamate and dopamine with an excess of glutamate
https://www.ncbi.nlm.nih.gov/books/NBK507255/
We go into this at our CBD and glutamate or CBD and dopamine in more detail.
As for magnesium levels and symptoms?
The increase in magnesium concentration can reduce anxiety, hallucinations and agitation whereas hypomagnesemia could exacerbate anxiety and hallucinations.
https://www.ncbi.nlm.nih.gov/books/NBK507255/
Zinc is also a big player (as well as acetylcysteine ie, NAC - see review ).
NAC and CBD have the most impressive research with schizophrenia and bipolar.
We did full reviews at CBD and schizophrenia or CBD and bipolar here.
Let's turn our attention to OCD.
Magnesium and OCD
We'll include the whole suite of excessive activity (especially from the emotional center - the amygdala) in this review.
Repetitive thoughts. Negative thoughts. Ruminations.
All shows hallmarks of impaired GABA and excess glutamate.
Check out CBD and OCD or CBD and repetitive thoughts .
First, the genes are partially pointing to glutamate/GABA imbalance.
There has thus been substantial excitement surrounding the association of the glutamate transporter gene Slc1A1 with OCD
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205262/
That link walks through a vast amount of research surrounding glutamate excess and OCD.
For example…
Recently, marble burying was observed to be attenuated by several antagonists of the NMDA glutamate receptor.
NMDA is the very receptor that magnesium plugs into.
When researchers blocked activity (antagonists) at this receptor (like what magnesium does), the animal version of OCD (marble-burying) was reduced.
Unfortunately, we do not have good studies on OCD and magnesium besides one which showed mag and zinc levels were reduced in people with OCD.
There's not much money to made from magnesium after all.
Check out CBD and OCD for more information but NAC would also be useful here as a sponge for excess glutamate.
The link above points to many different chemicals that reduce glutamate function or remove the excess amount outside the neuron.
Such as rizolule:
A positive clinical response (defined as a 35% improvement in the Y-BOCS score) was seen in 7 of the 13 patients in this original study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205262/
Another inhibitor of glutamate is memantine and from one study:
They found substantially greater improvement in the OCD patients (40.6% Y-BOCS improvement for the group) than in the GAD patients (22.4% improvement in the Hamilton Anxiety Rating Scale). This suggests that benefit from memantine may be specific to OCD, and not a nonspecific effect on anxiety.
Again, magnesium, CBD, and NAC are very safe and have much better side effect profiles but the same pathway is in play.
You can see how anxiety is commonly assoicated with OCD and some researchers think of OCD as falling under the umbrella of OCD.
Look at NAC's results:
The YBOCS score of NAC group significantly decreased from 21.0(8.2) to 11.3(5.7) during this study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483239/
YBOCS is a scale for OCD severity.
Just look at some of the symptoms of magnesium deficiency (estimated at around 70%) in the context of OCD:
You might especially want to try this if you have any of the other classic symptoms of magnesium deficiency: muscle spasms and cramps, all-over muscle pain, tics, and eye twitches.
Tics. Eye twitches.
Let's turn to panic attacks.
Magnesium and Panic Attacks
Panic attacks are a combination of anxiety with an activation of our fight or flight system.
The latter piece involves our HPA axis (hypothalamus pituitary adrenal) which prepares the body and brain for fight or flight. Adrenalin and cortisol!
The same rules apply with glutamate and panic as did with anxiety above.
Magnesium administration decreases anxiety, panic and phobia and ameliorates the attention deficit and sleep disorders.
https://www.ncbi.nlm.nih.gov/books/NBK507254/
Magnesium is heavily involved in both our stress response and our fight or flight response.
In fact…
Low Mg/Ca ratios augment the release of catecholamines in response to stress
https://www.ncbi.nlm.nih.gov/books/NBK507250/
Catecholamines include adrenaline (epinephrine) and its precursors. THE fight or flight chemical.
A drop in mag literally starts the process of fight or flight when stress is present!
This creates a vicious cycle as magnesium gets pulled out of cells into the spaces between and more gets excreted by urine.
As researchers put it:
Moreover, stress and hypomagnesemia potentiate each other’s negative effects in a veritable pathogenic vicious circle.
https://www.ncbi.nlm.nih.gov/books/NBK507250/
Guess where that circle ends?
Panic attacks!
Check out CBD and panic attacks or NAC. Vitamin C is known to bring down cortisol response as well.
Remember, panic is characterized by a severe imbalance between GABA and glutamate with HPA axis response to follow:
GABA antagonizes glutamate hyperexcitation in some brain regions such as the dorsomedial hypothalamus and protects against anxiety and panic disorders
https://www.ncbi.nlm.nih.gov/books/NBK507254/
That hypothalamus is the "H" in HPA!
Let's turn our attention to PTSD.
Magnesium and PTSD
We've covered PTSD in detail here.
There are two aspects at play which magnesium which affect on.
First, you have the HPA fight for flight response we looked at above with panic attacks.
More importantly, we have structural changes in the brain as a result of the trauma and a block between actual pathway modes of brain activity.
We've looked at how magnesium is intimately involved in the entire stress to adrenaline feedback circuit (as a dampener).
A study looked at magnesium following traumatic brain injury:
In contrast, animals treated with MgSO4 had a mean activity score of 144 23 at 1 week after TBI and an incidence of depression/anxiety of less than 30%. The significant difference between groups persisted for the entire 6-week observation period.
Magnesium's effect on BDNF (our brain's fertilizer) may be more critical for long term improvement.
In fact, the studies on psilocybin (review here ) and PTSD are profound and it primary works to significantly boost BDNF and reset the default mode network being stuck.
BDNF is key to rewriting our brain pathways. No change occurs without it and PTSD is reflects a brain stuck in trauma.
Researchers are starting to wonder if neurogenesis (the architect that uses BDNF) might be part of why some people go through trauma and don't experience PTSD:
We found that BDNF serum levels were lower in PTSD patients as compared to related control subjects.
https://pubmed.ncbi.nlm.nih.gov/24362070/
The PTSD itself may be reducing BDNF which occurs with some addictions.
The repair mechanisms just are not keeping up.
Here's where it gets interesting….they're finding that magnesium can increase "plasticity", the rewiring of the brain specific areas which benefit fear extinction.
The current study suggests that elevation of brain magnesium might be a novel approach for enhancing synaptic plasticity in a regional-specific manner leading to enhancing the efficacy of extinction without enhancing or impairing fear memory formation.
https://pubmed.ncbi.nlm.nih.gov/22016520/
Let's decipher that because it's too fascinating.
Essentially, mag would boost BDNF and other activities needed for removing existing "imprints" of past fear while not impeding new formations.
It did this by targeting specific brain areas differently!
We covered CBD and PTSD in great detail since its effect on fear extinction is profound.
Again, they're talking about "past" fear imprints on our brain circuitry.
These imprints prime our current responses so this is very important for past trauma.
These findings provide the first evidence that CBD can enhance consolidation of extinction learning in humans and suggest that CBD may have potential as an adjunct to extinction-based therapies for anxiety disorders.
https://pubmed.ncbi.nlm.nih.gov/23307069/
Magnesium, CBD, and NAC could be very interesting here.
Magnesium and ADHD
Interestingly, acetylcholine may be the main lever for ADHD (see acetylcholine review here ).
That's why nicotine is effective, albeit with downsides (addiction and tolerance).
Look at this study with magnesium for children with ADHD:
In the group of children given 6 months of magnesium supplementation, independently of other mental disorders coexisting with hyperactivity, an increase in magnesium contents in hair and a significant decrease of hyperactivity of those examined has been achieved, compared to their clinical state before supplementation and compared to the control group which had not been treated with magnesium.
https://pubmed.ncbi.nlm.nih.gov/9368236/
Looking at a review of many studies, there was a striking consistency between ADHD symptoms and mag levels:
The random-effects meta-analysis showed that subjects with ADHD had 0.105 mmol/l (95% CI: -0.188, -0.022; P < 0.013) lower serum magnesium levels compared with to their healthy controls.
https://pubmed.ncbi.nlm.nih.gov/30807974/
Another study looked at Vitamin D and mag together:
Supplementation with Vitamin D and magnesium caused a significant decrease in conduct problems, social problems, and anxiety/shy scores; but it had no significant effect on psychosomatic problems score.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011463/
The relationship between Vitamin D and mag is intricate, many, and fascinating:
Vitamin D supplementation could elevate serum magnesium levels.[30,31] Furthermore, serum levels of Vitamin D might be affected by magnesium intake.[32] In addition, magnesium might affect Vitamin D metabolism.[33,34]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011463/
Zinc and B6 also show up in other studies with significant results.
Acetylcholine is all the rage for dementia research (maybe the linchpin).
Look at what mag does there:
A study in patients with different diagnoses showed low enzyme activity of choline esterase in erythrocytes. Administration of magnesium resulted in normal catalytic activity of choline esterase.
https://www.karger.com/Article/PDF/345486
Choline esterase is the main enzyme needed to make acetylcholine.
They were able to boost this pathway with mag supplementation alone.
Research on NAC and CBD are also front and center but supplementing with choline (CBD choline here) may be essential.
Researchers at the University of Colorado at Denver, Aurora, proposing that a form of choline may prevent the development of autism, ADHD, and schizophrenia by an epigenetic mechanism involving a nicotinic acetylcholine receptor
Goodness...the rate of vitamin d deficiency is very high across the population. Make sure to get yours tested before supplementing.
This has a knock-on effect for both magnesium and acetylcholine!
All of which are tied to ADHD symptoms.
Let's look at general mood and when it goes wrong...neurosis.
Magnesium and mood
Mood is generally under the tight reigns of serotonin. Not too high. Not too low.
Being the 4th most abundant mineral on Earth, you can bet mag is involved in the serotonin pathway.
Mg acts like a cofactor for tryptophan hydroxylase, intervenes in serotonin receptor binding in vitro and exhibits a direct enhancing effect on 5-HT1A serotonin receptor transmission
https://www.ncbi.nlm.nih.gov/books/NBK507250/
Goodness. Serotonin is our primary stress buffer (along with anandamide which CBD boosts) and not only is mag needed to create it from tryptophan but it boosts its level at the receptor.
Essentially, it's working like an SSRI without the nasty overshoot and tolerance (see CBD versus SSRIs or how SSRI's actually work ).
In fact, research shows that SSRI boost mag! Maybe that's their trick to begin with??
Specifically:
The bioavailability of magnesium affects the function and binding of neurotransmitters to their receptors, such as serotonin and dopamine
https://www.zrtlab.com/blog/archive/mineral-imbalance-adhd-magnesium/
Tryptophan and CBD also significantly support and/or rescue serotonin function within ranges which is important.
Too much serotonin is just as bad as too little.
Every aspect of mood from crying to rage; from apathy to engagement...even our self-confidence rides on serotonin function.
Check out our Self-esteem review with serotonin setting prominently.
Fascinating research there.
Then there's neurosis. Basically, personality types which are impaired.
A study looked at personality traits between orphanages and state schools with the following interesting connection:
The positive correlation in magnesium deficit-neuroticism suggests that magnesium deficit may be a causal factor in this negative aspect of personality.
https://www.ncbi.nlm.nih.gov/books/NBK507254/
That link has many such examples for magnesium and behavior, especially in light of serotonin.
Over 325 enzymes need magnesium to function properly and DNA synthesis of serotonin is one of them.
In, fact the conversion of tryptophan to serotonin is critical for mood in general and look at mag's role:
Mg acts like a cofactor for tryptophan hydroxylase, intervenes in serotonin receptor binding in vitro and exhibits a direct enhancing effect on 5-HT1A serotonin receptor transmission
https://www.ncbi.nlm.nih.gov/books/NBK507250/
Let's turn to another health issue where glutamate is running too hot.
Magnesium and seizures
You can think of glutamate imbalance as being on a spectrum.
- Small levels of excess glutamate - excitability and intensity
- Higher levels of excess glutamate - irritability and "frazzled" effect
- Still higher levels - seizures!
Seizures, whether epileptic or not, are driven by imbalances between glutamate and GABA.
Researchers are now pinpointing exactly how this happens:
Taken together, these results strongly suggest that the observed seizure-induced high flux of glutamate overstimulated glutamate receptors, which triggered a chain reaction of excitation in the CA3 recurrent glutamatergic networks.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174845
Essentially, too much gas pedal sets off a chain reaction that spreads through the brain.
We know from above that magnesium blocks glutamate activity so is there a connection there?
Simply put:
Clinical and experimental investigations have shown that magnesium depletion causes a marked irritability of the nervous system, eventually resulting in epileptic seizures.
https://pubmed.ncbi.nlm.nih.gov/1919610/#:~:text=Abstract,correction%20may%20prove%20life%2Dsaving .
A study looked at infantile seizures and compared adrenal corticotrophin hormone by itself or combined with magnesium and the results were:
At 12 weeks, 14 patients (73.7%) who received ACTH + MgSO(4) and 9 patients (47.4%) in the control group were seizure free.
https://pubmed.ncbi.nlm.nih.gov/20435238/
Maybe more importantly as a result:
Personal-social neurodevelopment was significantly improved from baseline in the group that received combination treatment.
We look forward to further research.
What about our two cohorts...NAC and CBD?
NAC exerts a dose-dependent anticonvulsant effect in acute and chronic uses, with no muscle relaxant activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359931/
As for CBD, this is how it was brought to fame:
In these studies, CBD was found to be superior to placebo in reducing the frequency of convulsive (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut syndrome.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767492/
Check out CBD and GABA or CBD and glutamate to understand why.
Finally, some practical questions.
What's the best kind of magnesium
Very little mag taken orally actually gets absorbed much less makes it past the blood-brain barrier.
The various "ates" fare much better.
Magnesium glycinate and Magnesium threonate are two of the top ones with citrate coming in third.
There are some good combinations such as Neuromag by LifeExtensions.
The standard mag you get at a CVS is pretty poor at actually getting into the nervous system.
Threonate is standing out in terms of nervous system function such as this one which looked at increasing synaptic density in the brain:
These effects are unique to threonate, as other common Mg(2+) anions failed to have the same results.
https://pubmed.ncbi.nlm.nih.gov/27178134/
Remember...BDNF, our brain's fertilizer needs magnesium to function.
Citrate has strong bioavailability (gets into bloodstream) but that's different from getting into the brain.
Threonate appears to be the reigning champion there.
I still swear by glycinate for migraines but there are plenty of sites that compare various versions.
Just know that the standard, magnesium oxide, is poorly absorbed.
What about dosage.
How much magnesium to take
Most of the studies above were from 200 - 400 mg of magnesium per day and the results generally occurred within a few weeks.
This is an ongoing, maintenance approach although one mag will stop a migraine in its tracks.
The general rule of thumb is this…
You can take up until you have diarrhea. Magnesium is a natural stool softener (in case you're ever constipated) and when you have too much, diarrhea will occur.
I personally take 3 a day at about 100 mg each. The bottles all reflect various serving sizes so be careful.
For example, 250 mg at two capsules so it's really 125 each.
The Neuromag is 2000 mg but that translates to 144 mg.
So...test and see what works with your system. I have found the 2-3 capsules a day works regardless of the mg breakdown.
Vitamin D is critical but you need to test your levels if supplementing.
We've only skimmed the surface of magnesium. It's safe to say that it's involved in almost every system of the body.
ATP, the very fuel of our cells is the most dependent on magnesium so if that's any indication.
Oh yes...and the making of DNA and RNA. So….important!
Be well!
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.