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Everything You Need to Know About Mixing MDMA and Antidepressants

It's difficult to get high when on SSRIs, but is trying to do so actually doing you any damage?
Hannah Ewens
London, GB

This article is part of "Safe Sesh", a VICE harm reduction campaign produced in collaboration with The Loop and the Royal Society for Public Health. Read more from the editorial series here.

SSRIs and MDMA don't make the best bedfellows. If you've been prescribed the former to treat your depression, chances are your enjoyment of the latter is going to be dented to the point that it's not really worth the whole rigmarole of picking up, crushing the MD down, putting it in your face and subjecting yourself to that distinctive toe-curling taste.


"I used to take MD every time I went out," says Nilu, 27. "But since I started taking SSRIs – from the age of 23 to now – I can't get high any more. The first time I took pills after starting the SSRIs I was like, ''Hmm, is this gonna work or will it be bad for my pills?' Every now and again I have a little dabble, but nine times out of ten it doesn't really work."

Charlotte, 31, has a similar issue. "I've been on and off SSRIs, and I find it extremely difficult to come up – which, when I was younger and impatient, meant I would double or triple drop and it would hit me an hour after everyone else and sometimes just not at all," she says. "It's well frustrating when everyone's on it and you're just sitting there waiting, trying everything you can to make something happen."

It's worth mentioning here that you definitely do not want to do that; taking a bunch of pills or MDMA in one go is where people run into problems, like having a just incredibly shit night, or ending up in hospital, or – worse – a morgue. Always start with a half and wait to come up on that before taking more, leaving a break of two hours between doses.

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For those who can't ever seem to come up, there's one thing to blame: serotonin – the neurotransmitter that plays an important role in the regulation of mood, sleep and appetite, and floods the brain when you take uppers like MD.


Dr Russell Newcombe, a drugs researcher specialising in harm reduction, uses a swimming pool analogy to describe how MDMA and SSRIs individually work on the brain's serotonin system.

"SSRIs mainly operate by stepping up the blocking of re-uptake, i.e. they stop the serotonin level from dropping off but don't increase it, hence preventing low mood," he says. "This is analogous to a swimming pool, in which water levels are kept constant by the water-recycling system. MDMA works on three stages of neurotransmission: it too blocks re-uptake, but it also boosts the release of serotonin from the presynaptic cell – analogous to water pouring into the swimming pool – and enhances reception on the postsynaptic cell. In short, the impact of MDMA use on serotonin in the synapse is a swimming pool in which the pumping of water into the pool is increased while the drains are simultaneously blocked. Result: the pool is flooded with water."

So they effectively cancel each other out, but does combining the two put you at any real risk?

Dr Newcombe says "not particularly", but that it would make the MDMA "less buzzy". Dr Ben Sessa, a psychologist who carries out psychopharmacology research, agrees. "The general rule is don't combine SSRIs with MDMA," he says, adding that, firstly, we don't know everything we need to know about this drug interaction; and secondly, reactions can be highly idiosyncratic and difficult to predict.


"Ideally, if you were taking MDMA, you wouldn't have any other medications on board," he says. "There's an urban myth that if you take a drug like prozac and then use MDMA you'll get a bigger hit, but it's absolutely not the case – the SSRIs reduce the effects of MDMA."

"You won't be getting the euphoric, psychological effects you want by taking more, but you will be getting more of the physiological effects – higher blood pressure, higher heart rate and higher temperature, which is a bummer,."

There are some very rare direct risks involved in using the two drugs together. "Both MDMA and SSRIs – in overdose – can cause something called the 'syndrome of inappropriate ADH', which upsets your blood metabolism and, in severe cases, can be toxic – so that's a reason to not combine the two," says Dr Sessa.

Again, the real danger lies in what both Charlotte and Nilu describe as a chase to catch up with their friends who aren't on antidepressants.

"You won't be getting the euphoric, psychological effects you want by taking more, but you will be getting more of the physiological effects – higher blood pressure, higher heart rate and higher temperature, which is a bummer," says Dr Sessa. "These are not normally dangerous. MDMA is a relatively safe drug. We know that because so many people take it and come to no harm. But in excessive doses, because you're trying to overcome the effect of being on the SSRIs, these may become dangerous."


I wonder out loud if there's any point at all in doing MDMA if you're on antidepressants. Dr Sessa clears it up for me pretty quickly: no. "All you're doing is taking MDMA to just feel hot," he says, "which is a bit crazy, really."

And it's not just this that sucks; unfortunately, even though you don't get the high, you'll definitely still get the low. Since your brain has been stripped of all that serotonin, you're going to be coming down with the rest of your friends, only they at least had a couple of hours of euphoria to help them justify the three days of wanting to cry all the time.

Beyond that, because so little research has been done on the topic, we don't know too much more. Dr Sessa says we still don't know what effect the MDMA could have on your antidepressants for the days after you take it, but that there's a strong possibly your SSRI medication won't be able to work to capacity when your serotonin levels are still out of whack.

Either way, if it's a choice between just sweating for hours while your mates soar off without you, then feeling fucking atrocious, versus simply carrying on as normal, I know which I'd rather pick.


More from our Safe Sesh editorial series:

Your Menstrual Cycle Affects Your Reaction to MDMA

We Asked Drug Dealers If They Care About Their Customers' Safety

How the UK's Festivals Changed Their Tune On Drugs