I’m a neuroscientist — what scares me the most about caffeine

Do you take your coffee with cream, sugar — or a side of brain damage?

“Caffeine in the neuroscience literature is genuinely terrible when combined with other drugs,” warned Dr. Natashia Swalve, a behavioral neuroscience professor at Grand Valley State University, in a recent TikTok.

One drug in particular has her especially alarmed, with early research suggesting it may pose hazardous risks when mixed with even small amounts of the stimulant. 

Roughly 90% of US adults consume some form of caffeine daily. The natural stimulant revs up the central nervous system, boosting alertness, focus and energy levels.

The FDA considers up to 400 milligrams a day — about four or five 8-ounce cups of coffee — safe for healthy adults.

But that safety threshold flies out the window when caffeine starts interacting with other drugs in your system.

“Caffeine actually increases the toxicity of blow, and it potentially increases the toxicity of ADHD meds,” Swalve said. “When combined with molly, it is particularly dangerous.”

Molly — also known as MDMA or ecstasy — is a synthetic psychoactive drug that floods the brain with serotonin, dopamine and norepinephrine, triggering euphoria, sharpened senses, increased sociability and a rush of energy.

In recent years, MDMA has gained attention as a potential therapeutic tool, but it’s still widely used recreationally at music festivals, nightclubs, raves and house parties.

National surveys estimate that 7.5% of Americans over the age of 12 have tried molly at least once.

But the feel-good high comes at a cost. The drug can bring on a host of adverse effects, including rapid heartbeat, muscle cramping and nausea.

It also disrupts the body’s ability to regulate temperature — essentially cranking up its internal thermostat — which can lead to a dangerous and sometimes fatal condition known as hyperthermia.

“In animal and cell studies, caffeine makes the hyperthermic effect of molly … far worse,” Swalve said. 

While caffeine alone doesn’t typically affect body temperature, research in rats shows that combining it with MDMA significantly increases both the peak temperature and the duration of the hyperthermic response — making users much more vulnerable to overheating.

“Caffeine also can increase the other problematic effects of molly,” Swalve said. “It can actually make the drug more neurotoxic, killing off those serotonin neurons in your brain.”

Serotonin plays a wide range of important roles in the body, supporting mood, sleep, digestion, appetite and even blood clotting and wound healing.

Animal studies show MDMA has the potential to inflict long-term damage on serotonin neurons, which may lead to memory issues, cognitive decline and mood disorders.

“Caffeine combined with molly might be even worse for those neurons, but the problem is that none of these studies have actually been translated into humans,” Swalve said. 

And it doesn’t take much to trigger the reaction.

Swalve notes that the interaction between caffeine and molly can occur at very low doses — like the amount in a chocolate bar or a third of a can of Coke.

“We think these things might interact in very dangerous ways, but we can’t actually really tell,” she said. “Right now we have no research in humans, and that is what actually scares me.”

Other potential risks of combining molly and caffeine include an increased risk of cardiovascular issues, depression, anxiety and serotonin syndrome — a life-threatening condition marked by confusion, high fever and a rapid heart rate.

In one study, mixing caffeine with molly increased the party drug’s lethality from 22% to 34% in rats.

“This is a huge problem,” Swalve said. “Barely anyone is thinking about the Red Bull they’re having while driving to that festival and how that might interact with the drugs they’re taking later.”

Although several studies have looked at caffeine-MDMA interactions in animals and cells, researchers have run into roadblocks when attempting to test the combination in humans.

Among them: molly is considered a Schedule I substance under federal law. These drugs are considered to have a high potential for abuse and no accepted medical use.

That has made it difficult for researchers to not only obtain molly, but also secure the funding and approvals necessary for such studies.

Ethical concerns also come into play. The potential dangers of combining two powerful stimulants raise major red flags about participant safety in clinical trials — and make recruiting test subjects even harder.

So, as scientists work to understand the short- and long-term consequences of mixing caffeine with other drugs, Americans will continue to sip, sniff, smoke and swallow a cocktail of prescription and recreational substances — often with little clue about the risks.

“I can’t guarantee that any of those together are safe,” Swalve said. “You probably are not even considering those interactions.”