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.

Spend your weekend downing pints, necking pills and intentionally blocking your nasal passages, and you're going to feel awful the following week. Stick to booze alone and the Revenge of the Big Bag of Cans will make itself known fairly quickly, i.e. immediately after you wake up. The aftereffects of other substances, however, can be less straightforward.

While the old adage "what goes up must come down" remains as true as ever here, some drug users have been known to report the fabled "afterglow effect" – a period after the party but before you feel like human trash, when your body and mind actually both feel pretty OK, or – in fact – actually good, the positive effects of the drug lingering around and banishing the comedown.

This all-too-rare feeling certainly doesn't crop up with all drugs. You'll be hard pressed to find anyone extolling the life-giving qualities of cocaine the morning after railing great big lines off a Black Swan DVD case. It's after taking MDMA in particular that this effect is typically reported, although both psychedelics and ketamine get a mention on online forums and in sesh lore for sometimes leading to positive next-day experiences.

It's a feeling that Georgio, 32, who takes MDMA about once a month, can relate to. "Yeah, I love it – the day after is almost my favourite," he says. "I think it's like, I wouldn't say it's the effect of the drug itself, but it's the way the the drug empties out, and that's what you're left with. You're left with this enjoyment. More with MDMA. I don't feel that much with psychedelics."

The phenomenon doesn't seem to affect everyone, though, and there are plenty of people like Laura, 34, who – despite a long and illustrious drug taking career – have never felt positive the next day. "It's a little bit different for me, I feel," she says. "When I take MDMA it's so overwhelming, the next day I feel totally drained. Not good at all."

Indeed, even those who do experience it concede there are other factors at play. Alex, 28, who takes "whatever he can get his hands on" most weekends, says that what he's taking alongside the MDMA matters most. "It depends on what you do," he explains. "Like, if you drink a whole bottle of whisky, then no. But if I only take drugs, then I always feel it."

What causes this mysterious effect? Is it purely psychological, the result of having a great night, making a bunch of new best friends and getting into funky house in a way you never thought you could? Or is there a pharmacological underpinning to this sensation?

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Harry Sumnall, Professor of Substance Use at the Public Health Institute, Liverpool John Moores University, says the evidence for any direct drug effect is scant: "Thinking about the clinical pharmacology of MDMA, there's nothing that we know about it that would suggest a robust pharmacological mechanism behind this," he explains.

MDMA causes a rapid release of neurotransmitters – in particular, serotonin and dopamine, noradrenaline and oxytocin – followed by depletion of these chemicals for up to a week. A pharmacological basis for the afterglow effect "would be in contrast to everything we know about depletion of these neurochemicals", says Sumnall.

Sumnall posits that MDMA metabolites could play some hand in the effects. One known metabolite of MDMA is MDA, a known psychoactive drug itself – however, Sumnall notes that as only 5 percent of the MDMA dose gets converted to MDA, its unlikely it would produce any noticeable sensation. Another potential culprit, he suggests, could be the prominent active metabolite called HMMA, which endures for several hours after the MDMA has dissipated – but no one has ever studied what effects it has on the body or people's emotions, other than raising heart rate and a few other basic reactions.

Another possibility comes from the structure of the MDMA molecule itself. MDMA, whether it's finding its way into your speckled pills and grubby baggies or being used for clinical trials, is made up of an equal mix of two forms – or "enantiomers" – which are seemingly identical but actually mirror images of each other. It has been shown using studies on mice that these two forms, (S)-MDMA and (R)-MDMA, have quite different, but complementary, effects on the body that combine to create the unique experience of the drug.

While (S)-MDMA exhibits the intense stimulant effects akin to other amphetamines, (R)-MDMA appears to be predominantly responsible for many of the more emotional effects of the drug. It has also been shown that while (S)-MDMA seems to be metabolised within a three to four-hour period, (R)-MDMA hangs around in the body for several hours longer. It has been speculated that the afterglow effect may owe its origins to the residual effects of any (R)-MDMA still present in the body, long after the (S)-MDMA has gone and you've stopped attempting to use your tongue as a soft chew toy.

Sadly, systematic investigation into either of these possibilities hasn't ever been conducted. Research concerned with the aftereffects of MDMA intoxication has been restricted to studying either the neurotoxicity of the drug, or the comedown itself, which Professor Sumnall describes as "midweek sub-acute depression and anxiogenic effects". Harry acknowledges it would be intellectually interesting to see if either metabolites or enantiomers of MDMA play a direct pharmacological role in adding some sparkle to the day after a sesh, but says there is more useful research that could be conducted around the behavioural cues that lead to people's experiences, and which confounding factors prevent some people from feeling the "afterglow", such as differing metabolic rates and pathways for different people.

Photo: Chloe Orefice

While it's tempting look for a direct pharmacological reason for the afterglow effect, Sumnall says the explanation is just as likely to be behavioural or psychological. "There's lots of these individual factors that may be important, but I suspect most of the evidence is pointing towards a learned or psychological effect," he offers.

The idea here is that the impact of the experience – not just the drug, but also factors like the music, the shared communal experience, or whatever else you're doing while you're high – produce a lasting positive psychological experience that causes you to reflect back positively in the following days. This explanation also ties in with anecdotal reports that newer users tend to feel the afterglow more strongly, as the experience is more novel and so has a greater psychological impact. Conversely, if you do everything in your power to make sure you're shattered the next day, any positive psychological experience goes up against your body telling your brain you feel awful.

This stance is backed up by Dr Ben Sessa, a psychiatrist and psychopharmacological researcher who has conducted a number of trials involving MDMA, including an upcoming study investigating whether MDMA-assisted therapy could be used to treat alcohol dependence. In a clinical setting, he says, where an appropriate dose of pure MDMA is taken in the morning and patients are well rested and cared for both during and after the therapy session, the afterglow effect is far more apparent and sustained, while any comedown is tangible in only a tiny fraction of patients. He suspects there are both psychological and pharmacological elements at play, but also points out that the two are interlinked anyway, so trying to differentiate them doesn't necessarily make sense.

"Pharmacologically, there is the possibility that MDMA causes changes in the brain that are just not the same [afterwards]," says Ben. "It might just be that it's novel, that it's interesting. You get a bigger buzz the first time you go to a football match or an opera, compared to the next 100 times you go."

Both Sumnall and Sessa stress that whether people are trying to avoid the worst excesses of the comedown or get a taste of the afterglow effects themselves, sensible self care measures such as rest, food, hydration, refraining from taking other drugs and not drinking a brewery, before, during and after taking MDMA, will all help your body and mind recover.

Georgio agrees with the experts here, and though he always notices the effects to some extent, he thinks your overall wellbeing is crucial. "I never miss it – it's always there," he says. "I feel like, if you don't have it, then it's more you're experiencing some negative things in your life; it's not the drug."

If you're taking MDMA to simply stay up later, dance harder, drink more alcohol and eat less food than you otherwise would, then it's no wonder you're not going to feel great the next day. The hangover, sleep deprivation, poor nutrition, overexercise and dehydration will far outweigh any afterglow, regardless of its actual causes, and guarantee that your "midweek sub-acute depression and anxiogenic effects" will be every part the living hell of self doubt and listless malaise that you were fearing.