A natural mineral mimics the intercellular effects of the anesthetic ketamine
an anesthetic and street drug known as “Special K” has garnered a lot
of attention for it’s ability, in some, to relieve the symptoms of very
severe depression in a matter of minutes. A recent study has demonstrated how it might work, but before you go signing up for a clinical trial (and there are currently many going on in the US),
it’s important to understand the downsides to the drug. One major
problem is that the effects wear off, usually within 10 days, leaving
you just as depressed as before. It can cause urinary incontinence,
bladder problems, addiction, and, with chronic use, it can worsen mental health problems, causing more depression, anxiety, and panic attacks.
from being recycled, leaving bunches of dopamine in the synaptic cleft.
In the very short term, you feel great. In the long term, you tax the
system by driving the neurotransmitter system far out of balance in an
aggressive way.
Nicotine has a similar effect on
the alpha-7 nicotinic receptor. It activates it in a pleasing way, but
unfortunately desensitizes the receptor so much that only nicotine will
keep it firing. A nutrient found in foods such as egg yolks called
choline activates the same receptor, but without desensitizing it. Long
term, regular ingestion of choline keeps the receptor functional and
happy, helping with certain brain
tasks. Long term, regular use of nicotine activates the receptor but
forces you to take more nicotine to keep the receptor working, leaving
you foggy-headed and less sharp if you go without cigarettes.
So
is there a less dramatic, “natural” version of ketamine, something we
can safely ingest every day, but might be a little depleted in our
modern diets? Nothing taken in physiologic amounts would reverse a
depression in half an hour like ketamine, but could another chemical we
find in food and mineral water help with resilience
to stress, synaptic repair, and make us more resistant to depression
and anxiety symptoms? Sure—that chemical is the mineral magnesium.
Magnesium, like ketamine, acts as an antagonist to the NMDA receptor,
which means it is a counter to glutamate, the major excitatory
neurotransmitter in the brain. The exact mechanisms are complex, but
both ketamine and magnesium seem to help glutamate do its job,
activating the receptor, without damaging the receptor with too much
activation, which, chronically, leads to excitotoxicity, synaptic
degradation, inflammation, and even cell death.
of the exciting things about ketamine is that it works in some people
with severe treatment resistant depression who have failed the
traditional therapies. Treatment-resistant individuals tend to have
lower intracellular magnesium levels than normal (1).
Ketamine and magnesium may also work synergistically, complementing
each other. Ketamine leads to an increase of intracellular magnesium,
and ketamine will reverse the normally seen magnesium decreases after
brain trauma (2). There is some evidence also that more standard antidepressant
medications, such as imipramine, work in part by reversing the
magnesium-depleting effects of chronic stress, suggesting that adding
magnesium supplementation to standard antidepressant regimens might help
the medications work better (at least in rodents) (3).
It’s
great to see an interesting compound like ketamine be taken seriously
and thoroughly studied for its action in serious, resistant depression.
Ultimately its usefulness may be limited to hospitalized patients who
can be closely monitored for the side effects, and who also may benefit
the most from the quick mechanism of action, while the longer term risks
may be outweighed by the short term benefit in such a critical, serious
situation. I would love to see a much safer compound, the mineral
magnesium, be studied as an adjunct treatment.
In the mean time,
magnesium supplementation is generally safe for most folks with normal
kidney function. Many folks eating a normal Western Diet have a low intake of the mineral (4).
Those with bowel obstructions, very slow heart rate, or dangerously low
blood pressure should not take it. Magnesium can interfere with the
absorption of certain medicines (digoxin, nitrofurantoin,
bisphosphanates, and some anti malaria drugs). Here are some excellent food sources
of magnesium (though remember that both nuts and grains have phytates,
which bind minerals, so the magnesium you absorb may not be quite as
much as the magnesium you ingest.) Magnesium is also available in many
mineral waters.
For more information about magnesium and the brain, please read my article here: Magnesium the Original Chill Pill. A nice paper from last year details the ketamine-magnesium connection if you have journal access (thanks to Drew Ramsey for pointing the paper out to me).
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