What Happens to Your Body and Brain When You Combine Different Drugs?

People don't often take their drugs in isolation. In fact, polysubstance use—a grand term for "getting fucked up with more than one drug"—tends to be the norm rather than the exception for most drug users.

You'll have a beer on its own, sure, or smoke a bit of weed without feeling compelled to email your accounts department at 4 AM, asking for a salary advance to blow on six more grams. But put anything up your nose and it's likely you'll end up supplementing that with something else—another upper on top of your existing upper, a downer to even you out when you want to go to sleep.

Despite its prevalence, polysubstance use is poorly researched, with most drug studies concentrating on the effects of single substances. One certainty, though, is this: With every additional drug you take, you increase the risk to your health exponentially. Case in point: the many celebrities who successfully take heroin or cocaine for years before injecting a speedball—a cocaine-heroin combo—and very publicly dying.

"There are different boxes of substances, stimulants, sedatives, hallucinogens, dissociatives. Combining more than one from each of those boxes can increase your risk," says Dr. Owen Bowden-Jones, founder of the CNWL Drug Club Clinic.

Bowden-Jones has conducted extensive research on club drugs and knows the effects on his patients. The combination of two uppers isn't a good idea, he says, since they "increase the heart rate and the blood pressure. Taking more than one stimulant can multiply this effect, increasing the risk of catastrophic harm, such as cardiac arrest or stroke." Same goes for two or more sedatives, he points out, as "the risks of extreme sedation or coma are heightened."

Combining drugs from different categories can be an equally bad idea. "Many users combine a sedative with a stimulant," says Bowden-Jones. "They try to balance the effect of one with the other, the sedative taking the edge off the stimulant high." The problem, though, is that it's easy to get the balance wrong: "People act as amateur psychopharmacologists, mixing drugs to get a certain effect—but what they judge poorly are the risks."

Aware that most people are going to continue taking two or more substances at a time, regardless of what that might do to them, we decided to ask a couple of experts—Bowden-Jones and Dr. Adam Winstock, founder of the Global Drug Survey—to talk us through the potential risks of some of the most common drug combinations.

This is a pretty common combination, with many casual cocaine users only really taking the drug if they've already been drinking. Unsurprisingly—given that one's an upper and one's a downer—it's not a mix that's very good for your heart, or your general wellbeing. However, it does create a whole new different kind of high in itself, which is possibly why so many people end up reaching for their phones once they've got a few beers inside them.

According to Bowden-Jones, "[Cocaine is a] stimulant and [alcohol is] a sedative. Co-ingestion leads to the formation of cocaethylene, which itself has a psychoactive property."

Studies suggest that while this cocaethylene substance might stick around longer in the blood than cocaine, therefore lengthening the euphoria, it also may be more cardio-toxic than cocaine, i.e. not good for you in any conceivable way.

Combining ketamine and MDMA is as common a drug combo as you'll get. Often people take MD to start their evening off, topping themselves up with bumps or bombs throughout the night, before getting the K in to either push them that bit further or help to bring them down once they're back in someone's living room and the sun's coming up and, inexplicably, Ultrabeat is on the stereo and they really don't want to be there any more.

Bowden-Jones says that, despite its popularity, he has seen "very little research" into the effects of combining the two drugs. "We know that ketamine can be a sedative and MDMA a stimulant, but judging the right balance of the two is incredibly difficult," he says.

Tom, a 24-year-old student, has experienced this while taking MDMA and, shortly afterwards, ketamine in the "momentum of a party situation." He had never taken ketamine before, but found the combination of drugs to cause a violent, rapid onset of his high.

"I could still feel the emotional connection you feel on ecstasy, but it was quite overwhelmed by the ketamine," he says. "Maybe I didn't feel quite as distressed about being in the K-hole because of the MDMA, though I generally didn't really like it overall."

According to Bowden-Jones, MDMA and acid is a far more unusual combination than MDMA and ketamine. He's right: It's not a mix that comes up too often on your average night out, which is probably a good thing, as combining the two stimulants leaves the user at "risk of getting both heart and blood pressure problems, as well as horribly intense hallucinations."

"Most people would drink some alcohol while they're on MDMA, which is not a great idea," says Dr. Adam Winstock, founder of the Global Drug Survey and, like Bowden-Jones, an expert in the field of polysubstance use. "The alcohol further dehydrates you and brings you down from the MDMA effect."

He says a glass of wine is OK, but not "two or three bottles, so it really depends on how much you drink. You're much better off drinking water, juice, or milk."

Combining weed and booze has traditionally been a great way to make yourself feel really dizzy and sick. If you enjoy purposefully making yourself feel like that, says Winstock, make sure to stay away from the wheel—or, if your designated driver has been smoking weed and drinking, make them sit on their hands until they're sober, then allow them to drive you home.

"The alcohol rapidly increases THC levels in your blood, so it makes you more stoned," explains Winstock. "Alcohol impairs driving, cannabis impairs driving, together they impair driving a huge amount."

"Weed is the most common [substance] people take to get rid of a nasty [MDMA] comedown," says Bowden-Jones. "They smoke weed or take sleeping pills at the end of the night."

The main risk this poses, if you're susceptible to that kind of thing, is the weed making you anxious and paranoid, compounding the anxiety and paranoia you're already experiencing thanks to your comedown. Mind you, of all the drug users we speak to, no one has anything particularly bad to say about mixing pot and pills.

"I've had plenty of nights when I'm buzzing my absolute twat off on MDMA and everyone just wants to smoke," says Matt, 24. "It doesn't do as much as normal, but still chills us out."

"When we asked people [in the Global Drug Survey] a few years ago what they thought the most dangerous [drug combination] is, most of them said ketamine and alcohol," says Winstock. "That is a smart answer, since alcohol hugely increases the bladder problems triggered by ketamine because of the dehydration. Also, it gets you sedated and you lose your balance, which increases the risk of getting into a K-hole."

So there you go: If you're drinking, stay away from the K.

"It's a really common combination," says Winstock. "The comedown from crack cocaine is very unpleasant; heroin is used to mellow that out."

With that in mind, the more crack you use, the more heroin you're going to use to balance yourself out, raising the risk of overdose.

GBL and GHB are big libido-drivers, and crystal meth or mephedrone helps to physically sustain that libido over a long period of time. However, they're all substances that can cause psychotic symptoms or paranoia, so combining them clearly isn't the best way to reduce the risk of experiencing those side effects.

"It's obviously a really common combination, particularly with people involved in chemsex," says Winstock. "GBL and GHB can reduce people's ambition when it comes to safe-sex practices, so apart from the unwanted physical effects there are also behavioral effects, such as an increase in high-risk sex and sexual assault."

This can lead to the transmission of STIs, facilitated by mephedrone drying out your skin, which can cause bleeding if you don't use enough lube.

While cocaine stimulates the heart, heroin depresses the lungs, which can cause simultaneous cardiac and respiratory arrest.

"It's dangerous, because you combine two very potent drugs and it's very hard to control since it's usually taken by injection—once you've injected it, there's nothing you can do," says Winstock. "People play a risky game seeing how they can get the best experience by balancing them."

The highest risk from this combination comes from people not recognizing their drug problem.

"You drink half a bottle of wine and take four codeine tablets, and you think, 'I don't have a problem, the doctor gave me these tablets,'" says Winstock. "But actually, the combination of those has a huge risk of overdose, and you can mix the three of those. Lots of people would be on prescription opiates and benzos, but [combined with alcohol] they can quickly make you stop breathing."

To take part in the Global Drug Survey 2016, click here.