Mixing Stimulants & Depressants: What’s Safe & What Isn’t?

Medically Reviewed

In 2009, a group several U.S. attorneys general began to investigate companies that were legally selling beverages that contained high amounts of caffeine and alcohol. Reports claimed that these drinks were quickly leading to blackouts, which is when a severe state of intoxication causes a lapse in memory. By 2010, more reports of college students who experienced blackouts and extreme intoxication made the news. The State of Washington banned the sale of a drink called Four Loko after it was involved in the hospitalization of nine teenage college freshman.

Though the students were underage, the drink only contained substances that are otherwise legal in the United States. So why did it have these intense effects that cause media and governmental backlash? The drink contained a mixture of stimulants and depressants, which can have some dangerous consequences.

Caffeine and alcohol are just two examples of psychoactive substances from these two broader categories of drugs. Cocaine, meth, opioids, benzodiazepines, and many other prescription and illicit drugs fall into one of these two categories. Is mixing them always dangerous, or is there a safe way to do it?

Learn more about stimulants, depressants, and what happens if you mix them.

How Stimulants and Depressants Work

Stimulants and depressants are pharmacological opposites in many ways. Stimulants work to excite the nervous system and increase activity while depressants slow down excitability in the nervous system. For that reason, taking stimulants may increase your alertness and wakefulness while depressants may make you feel drowsy and calm.


Depressants are often GABAergic, which means they influence a neurotransmitter called gamma-aminobutyric acid (GABA). This naturally occurring chemical is responsible for managing excitability in the nervous system to help you calm down and rest. People with sleep and anxiety disorders may have physiological or psychological issues that disrupt this process and prevent them from relaxing when it’s appropriate. Depressants are used to treat issues that cause an overexcited nervous system like anxiety disorders, insomnia, and seizures.

Depressants like alcohol and benzodiazepines bind to GABA receptors on a separate binding site to GABA’s own spot. Once they are on their receptors, they can increase GABA’s effectiveness. Depressants like benzodiazepines can give GABA the boost it needs to ease your anxiety symptoms, suppress seizures, and facilitate sleep in people with insomnia. Depressants can also slow the nervous system down to the point of intoxication, with side effects like sedation, loss of motor control, slurred speech, and lowered inhibitions.


Stimulants are psychoactive drugs that increase the excitability of your nervous system and make you feel more alert, energized, and focused. Stimulants typically work by interacting directly or indirectly with dopamine, a naturally occurring chemical in the brain. Dopamine is responsible for several functions in the brain, and it’s closely tied to reward and motivation. Caffeine indirectly affects dopamine by binding to a related receptor. More powerful drugs like cocaine influence dopamine by blocking a process called dopamine reuptake, which is a process that removes an excessive chemical from your system. The resulting dopamine build up causes stimulating results.

Stimulants are used to treat attention deficit disorders. People with ADD and ADHD often have a deficiency of dopamine in the brain, and stimulants like Adderall can help balance brain chemistry. However, stimulants can also cause anxiety, panic, irritability, and euphoria. People that use drugs like cocaine recreationally are seeking a euphoric rush or an intense feeling of empowerment. Powerful stimulants like meth can also damage dopamine receptors in a way that makes them less effective. This can lead to an inability to feel pleasure that leads to deep depression.

Why Mixing Stimulants and Depressants can be Dangerous

One of the reasons stimulants and depressants can be dangerous is because they can give you a false sense of sobriety. Stimulants can lessen or delay the feeling of intoxication that comes with taking a depressant like alcohol. Taking the two at the same time can cause effects that counter each other. While one chemical is slowing down your nervous system and causing sedation, the other is making you feel alert and awake. In movies and TV shows, people often order a cup of coffee to sober someone up. But that doesn’t actually work. In reality, it just makes you feel more awake and alert, but you will still have the same amount of alcohol working in your brain. This can cause you to feel like you can drink more.


In the case of the nine students that were hospitalized after a night of drinking Four Loko, they were found to have blood-alcohol levels as high as 0.35 percent, while 0.30 percent can be potentially lethal. In addition to Four Loko, they were drinking other hard liquor. Under normal circumstances, they might feel severely intoxicated and even pass out before getting to that level.

Besides the active ingredients of a Four Loko, another notable stimulant/depressant combination is known as a speedball, which includes cocaine or methamphetamine and heroin. Heroin is an opioid, which means that it works differently in the bottom than most other depressants. Instead of acting on GABA receptors, they bind to opioid receptors, which results in depressing effects in the nervous system. Heroin can cause sedation, euphoria, and a warm, flushing feeling. Heavy doses can cause respiratory depression, which is when your breathing slows or stops.

Speedballing is supposed to offer the simultaneous effects of both drugs, including euphoric relaxation with an intense rush. However, the mixture can be deadly and can cause confusion, blurred vision, paranoia, mental impairment, and dangerous cardiac symptoms. Fatal overdoses that involved both cocaine and heroin often resulted in cardiac arrest. However, a speedball can also cause stroke, aneurysm, and psychiatric disorders.

When is it Safe to Mix Stimulants and Depressants

It’s generally wise to avoid mixing these two drug classes. However, if you do mix the two drugs, it should be with a doctor’s recommendations. In some situations, medication may contain caffeine to offset drowsiness or feelings of sedation. It may also be safe to take mild, over-the-counter medications that contain caffeine like Midol alongside your prescription depressants. However, you should still check with a doctor before mixing any medications.

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