Lithium: The Next Trend in Microdosing?

Low levels of the naturally occurring, soft shiny metal could reduce violence and enhance moods for all.

If I were to tell you that there’s a simple, single substance you could add to your diet that would lower your risk of depression and suicide, reduce the chances of violent crime plaguing your neighborhood (if enough people took it), and possibly even protect you against mental decline and the ravages of dementia from diseases like Alzheimer’s, would you believe me? Would you want to take it? How about if I told you that if you live in a region known for its prized spring water, you might be taking it already every time you turn on the tap?

The substance  I’m referring to is a metal, one of the elements in the periodic table, and found in abundance on Earth. But it’s not even one of the well-known supplements found in health food shops such as iron or calcium—or even a more fringe “micronutrient” like zinc or selenium.

It’s lithium: a silvery white metal that’s soft enough to cut like cheese and sizzles violently when dropped into water. It makes up the powerhouse of cellphone batteries, is dispensed as a life-saving drug to people with severe bipolar disorder, and is found naturally in groundwater around the world (as well as huge deposits, such as the Salar de Uyuni salt flat in Bolivia). 

Most of us probably first became familiar with lithium’s psychiatric use from Kurt Cobain’s self-deprecating crooning in the eponymously titled 1990 track “Lithium” (I’m so happy / ’cause today I found my friends / they’re in my head / I’m so ugly / that’s okay, ’cause so are you …). We might therefore be forgiven for mistakenly thinking, based on Cobain’s sad demise—suicide by shotgun at the height of his fame in 1994—that lithium carbonate (Li2CO3) tablets are only given as a last-ditch attempt to help the desperate because they come with brutally debilitating side effects.

Such prejudice is unjustified. It’s true that high doses of lithium given long term can indeed cause severe kidney and liver damage—as is the case with many pharmaceuticals. But for many people suffering from severe bipolar, a hefty dose of 600–2,400 milligrams a day of lithium carbonate can alleviate the exhausting highs and debilitating lows that can make life too much to bear. And the truth is that lithium has had remarkable staying power throughout the changing trends in pharmaceutical medicine, and it is one of the most enduring mood-stabilizing drugs in modern psychiatry. While antipsychotic and antidepressant medications have evolved over time—few pharmacopeias still contain sweet, sleepy barbiturates or wacky, zany Quaaludes (also known as “disco biscuits”), both of which could be lethal (especially if abused or mixed with alcohol)—lithium carbonate tablets remain unchanged as a treatment for bipolar disorder, a condition previously called “manic depression.” And thirty years of evidence suggests that tiny, daily doses of lithium just one-thousandth the size of a pharmaceutical dose can lighten the load of everyday life for everyone—a “microdose” of lithium, if you will.

“It seems to reduce net crime, and keep everyone in a less aggressive, more mellow mood.”

“Our research implies that low levels of lithium in drinking water stabilizes mood at the population level in every way,” says epidemiologist Anjum Memon of the University of Sussex, the lead author of a new meta-analysis of past studies published in the British Journal of Psychiatry that brought together data from 15 different ecological studies across the world that examined how naturally occurring lithium in tap water correlates with lower levels of suicide in local populations. Memon attributes those declines to the “mood stabilizing effects” of the metal. “It seems to reduce net crime, and keep everyone in a less aggressive, more mellow mood.”

Since the early 1990s, scientists across the globe have found that regions with higher levels of lithium in water experienced lower levels of suicide, depression, and even violent crimes such as rape and murder. In 1990, an analysis of police records from 1978–1987 in 27 different counties in Texas published in the journal Biological Trace Element Research found that rates of violent crime were significantly higher in counties with little or no lithium in the water compared to regions with higher levels (ranging from 70–170 micrograms per liter). Even arrests related to drug addictions were lower.

Similar studies from Japan, Portugal, Greece, Italy, and other countries have found the same—which is hardly surprising, considering that chemists have believed for over a century that lithium (sometimes called “the magic ion”) has healing properties, drawing inspiration from the respect shown by indigenous peoples for waters rich in lithium: “Lithia Springs” in Georgia and Virginia were revered by American Indians as sacred for thousands of years, as were lithium-rich springs in Chile and Argentina.

By the 1880s, shrewd entrepreneurs began to capitalize on supposed benefits with “lithiated” beverages—most famously, 7-Up, which was initially known as “Bib-Label Lithiated Lemon-Lime Soda,” marketed as a soothing tonic to mellow fussy babies (in the same manner that cocaine-infused Coca Cola was branded as a perky pick-me-up). It was only in 1949, when Australian psychiatrist John Cade rediscovered the therapeutic ability of the ion to treat “mania,” that beverage makers were banned from adding it to libations. The initial medical interest in lithium came a century before, and the first known prescription for lithium citrate as a treatment for bipolar—or “brain gout” as it was once known—is believed to have been written in 1871 by William Hammond, professor of Diseases of the Mind and Nervous System at the Bellevue Hospital Medical College in New York. But it was not until Cade that doctors began seriously testing lithium salt tablets for treating bipolar depression. By the late 1960s, dozens of countries were prescribing it to people with depression—though lithium salt tablets were not formally approved by the U.S. Food and Drug Administration (FDA) as a treatment for bipolar depression until 1970. 

The effects can be rapid and profound. “When I was a young resident doctor, I treated an elderly lady suffering from antidepressant-resistant depression with frequent suicide attempts. I added lithium to her ongoing antidepressant prescriptions after reading about it, and she dramatically recovered within a day,” says psychiatrist Takeshi Terao of Oita University in Japan, author of another new study in the journal Bipolar Disorders, which found lower rates of suicide across 808 cities and wards in Japan corresponding with higher levels of lithium in the water. “In my opinion, trace lithium does not have the ‘mood stabilizing’ effects which appear at high levels, but anti-aggressive and anti-impulsive effects can appear at very low levels,” he says.

Why is this so? One explanation for lithium’s “magic” properties is the extremely small size of the atom. The third element in the periodic table, with an atomic weight of just seven (supposedly the origin of the name “7-Up”), the tiny, nimble lithium atom can squiggle into every nook and cranny in the human body, even crossing the blood brain barrier (a feat larger molecules cannot accomplish). In the brain, it can nestle into the ion channels of nerve cells normally used by larger sodium and potassium ions. Just how this tiny, metal atom manages to produce such profound psychiatric effects is currently unknown to science, but a 2014 review of evidence from animal and cell cultures, published in the journal ACS Chemical Neuroscience, indicates that lithium is actually “neuroprotective.”

Lithium’s range of beneficial effects, from mood modulation to neuroprotection, may be linked to its ability to boost levels of certain enzymes and other large molecules—in particular the protein known as brain-derived neurotrophic factor (BDNF). Sometimes called “brain fertilizer,” this protein fosters the growth of new brain cells and is normally stimulated by healthy activities such as exercise. (It’s the reason why I always tell myself, when I don’t feel like dragging myself to the gym, “This is more for my brain than it is for my body.”) But cell culture studies suggest that tiny lithium doses can also boost BDNF; raise levels of vascular endothelial growth factor (VEGF); reduce levels of “oxidative stress”; modulate levels of neurotransmitters such as dopamine, serotonin, and glutamate; and reduce inflammation in glial cells (the “support” cells for neurons, essential for brain function).

A handful of studies also seem to suggest that lithium’s cellular trickery could even help protect against the development of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Experiments in rats have indicated that small doses improve memory and learning, and a 2017 epidemiological study from Denmark published in the journal JAMA Psychiatry found that long-term exposure to low levels of lithium in drinking water correlated with lower levels of dementia. And a 2013 study published in Current Alzheimer Research found that lithium doses could stabilize cognitive impairment in Alzheimer’s patients. Correlation of course does not prove causation, but the evidence is so persuasive, Terao says, that his next research focus will be lithium as a prophylactic for dementia.

The ethics of adding any mood-altering drug to the public water supply are dubious.

Given its ability to minimize the misery caused by violent crime and suicide, combined with the potential to mellow our emotions and protect us from mental decline, should we add lithium to our tap water as is routinely done with fluoride?

Absolutely not, says Memon (noting that very few regions in Europe add fluoride to drinking water in the first place). The ethics of adding any mood-altering drug to the public water supply are even more dubious—lithium, remember, takes away the highs as well as the lows, which is not appealing to everyone. Moreover, lithium has many “off target” effects: Like alcohol, some have called it a “dirty drug” for its ability to invade every cell in the body, and people who take high levels of lithium for bipolar disorder are at risk of severe and often irreversible kidney damage. Terao agrees, saying that forcing lithium on an entire population would be unethical. He suggests lithium could be added to clearly labeled bottled waters for those who are already prone to depression or low mood.

Over in Poland, chemist Piotr Rzymski has also investigated the question of whether or not lithium should be considered an “essential micronutrient.” Instead of adding it to our drinking water, he thinks we should consider artificially adding it to food, as we already do with iodine in salt and folic acid in grains. He reported in 2017 in the Journal of Food Science Technology that culinary mushrooms could be grown in lithium-rich soils, producing food that is high in lithium but unaltered in taste and appearance. “Cultivated mushrooms are increasingly popular, relatively inexpensive and easy to grow, and already known to bioaccumulate or even bioconcentrate certain elements,” he says, which makes lithium-enriched mushrooms an easy option for those seeking to harness the “magic ion” without having to move to a sacred spring (or dabble in pharmaceuticals).

Of course, anywhere evidence is thin but seductive naturally follows the snake-oil salesmen: Right now you can order low-dose lithium supplement pills online for $15. But some experts are not convinced. “I don’t see any rationale for their use,” Rzymski says. “These products are not pharmaceuticals but food supplements—and in my opinion, the use of supplements must be based on a defined indication, such as a deficiency. Claims on product labels that lithium is an essential element for bones and brain are simply not justified.”

Despite all our technological progress, shiny gadgets, and endless distractions, modernity has not made us happier.

Nevertheless, people are hungry for new mental health curatives—and for good reason. Despite all our technological progress, shiny gadgets, and endless distractions, modernity has not made us happier. Suicide remains the second most common cause of death in people aged 15–29, and it is responsible for 800,000 deaths worldwide every year. Moreover, bipolar disorder affects 1 in 100 people globally—yet lithium is little discussed outside psychiatric circles. A recent paper in the journal Neuropsychopharmacology calls lithium “an underutilized treatment in the United States.”

Why should this be so? Writing in the New York Times—hardly a hippie rag—a psychiatrist at Weill Cornell Medical College stated the obvious in an editorial six years ago: “Pharmaceutical companies have nothing to gain from this cheap, ubiquitous element.” Pharmaceutical companies cannot patent lithium, just as they cannot patent oxygen. With no profits to be made in our capitalist health care system, there is simply no incentive to fund lithium research or promote its use.

Perhaps we might consider the “magic ion” the same way we do sunshine: In high doses it can burn us, harm us, even spawn cancers. But in tiny doses as a daily tonic it could rescue our brains and our bodies from what might feel like the intractable misery of modern society. It’s plentiful and cheap, and easy to obtain without a prescription, perhaps in palatable and uncontroversial ways.

Lithiated mushrooms, anyone?

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