What Happens When You Mix Antidepressants with Recreational Drugs?

Taking recreational drugs when you are on a course of antidepressants can cause comedowns, anxiety and muscle spasms.
Photo: Anton Dos Ventos / Alamy Stock Photo

Just under one in six of England’s adult population are on antidepressants, while one in ten admit to using illegal drugs. This crossover poses a few potential problems: when combined, antidepressants and recreational drugs come with their own set of side-effects and risks. 

But even though there are strong links between drug use, dependence and depression, there is little information out there about what happens to your body when you mix these drugs. So we spoke to some experts to gain a better understanding.  



The impact of mixing cannabis and antidepressants can depend on the different types of both drugs, says James Giordano, a professor of neurology and biochemistry at Georgetown University Medical Centre in Washington DC. “If the cannabis has a slightly higher THC value, you’re going to get more of the arousal effect, the euphoria effect and, in some cases, anxiety,” he says.

Tom, 25, was on antidepressants from the age of 16 to 22, and used to smoke weed daily. “When I smoked on antidepressants, sometimes I’d get so anxious,” he says. “If I smoke now, when I’m not on them, I can usually shrug off any anxiety.”

Any cannabis comedown may also be extended by taking antidepressants, says Giordano: “As the cannabis begins to wear off, people can get a bit of rebound agitation, and it can make some individuals feel unresponsive or emotionally flat. The effect that the antidepressant drug has is that it extends this comedown a bit longer.”

Giordano’s main concern is mixing high THC cannabis products with a type of antidepressant called monoamine oxidase inhibitors (MAOIs): “With cannabis products that are higher in THC, you might start to see some cardiovascular effects. This is because MAOIs can increase the availability of norepinephrine in our system, which can lead to altered cardiovascular responses, such as changes in blood pressure, heart rate and rhythm.”



MDMA is known for its euphoric high, but when 22-year-old Dora started taking it while on a course of selective serotonin re-uptake inhibitors (SSRIs), she barely felt a thing. “I would look around and I felt like everyone else was having such a better time than me,” she says. “I was at 10 percent, and everyone else was at 100 percent.”

This reaction – or lack thereof – is not uncommon for people on a stable dose of antidepressants, says Adam Winstock, an addiction medicine specialist and the founder of the Global Drug Survey. “People who are on antidepressants and have been for some while will report blunted emotional responses with MDMA. That’s due to competition at the transporter site.” MDMA causes a greater release of serotonin, which provides that sense of euphoria. But SSRIs regulate serotonin levels, preventing them not only from dropping off, but from surging too. 

By taking more MDMA to try to reach that high, Winstock says that those on SSRIs not only risk the same adverse effects of MDMA as others, they also risk suffering from serotonin syndrome. This is where too much serotonin floods into your system. Symptoms include irritability, muscle rigidity and spasms, confusion and nausea, and if left untreated it can even become fatal.

Winstock says, therefore, that “the advice for people who are on stable doses of antidepressants has to be: don’t take an E”.



Taking cocaine, another stimulant, while on antidepressants also puts you at risk of too much serotonin flooding your body. Winstock warns that cocaine can severely undermine the effects of antidepressants.

“I always think that antidepressants are like putting a plug in the sink, because you’re trying to fill your brain up with good chemicals,” he says. “And what coke does is pull the plug out.” While you may still get that short-term euphoria, the comedown will be “dreadful”.

This is what happened for Ben, 21, who took cocaine during a “particularly low” part of lockdown. “I remember a heightened sense of anxiety while I was coming down,” he says. “But I think this partly came from me worrying that, by mixing coke, [the antidepressant] fluoxetine and alcohol, I’d really fucked up.”


When Emily, 22, was first prescribed antidepressants at 16, she continued her weekend ritual of binge-drinking at parties. Over time, she realised it wasn’t good for her. “Alcohol used to lead to an increase in suicidal thoughts for me,” she says. “All my suicide attempts were usually after I’d been drinking, or while I was still drunk.”

Many people suffering from depression are also likely to drink, but “alcohol will stop a lot of antidepressants working”, says Winstock. He says this is because alcohol alters the ability of the antidepressant to change your chemical imbalance, and can exacerbate your mood. So, if you’re already depressed or anxious, you could feel worse.

Different drugs and doses will react in different ways to varying types of antidepressants. And, of course, everyone has unique physical responses to drugs and drug mixtures. 

“We treat so many people who have ‘dual diagnosis’, where they have a drug and mental health problem,” says Nuno Albuquerque, treatment lead at UK Addiction Treatment (UKAT). “How a person reacts to drugs always differs depending on both their physical and psychological situation at the time of use.”

If you’re taking antidepressants and you want the best possible outcome, Winstock advises taking your medication every day and avoiding things that could reduce its effectiveness, such as recreational drugs. “People should never stop taking their antidepressants suddenly in order to take recreational drugs”, he says.