MDMA, commonly referred to as ‘molly’, is one of the most popular recreational drugs in the world, especially among young people in the nightclub scene. Commonly ingested in its pill form, known as ‘ecstasy’, MDMA produces both psychedelic and stimulant effects that amplify the euphoria of a rave. But last night’s high rapidly turns into the next day’s low as the drug wears off.

However, the molly blues that so many weekend warriors loathe may not actually be caused by MDMA (3,4-Methylene-dioxymethamphetamine), scientists claim — at least not by the drug in its pure form and when taken at the proper dosage. Instead, researchers believe MDMA comedowns are more likely caused by the numerous impurities found in street MDMA, the ill-advised combination of alcohol and other drugs, and lack of sleep.

The mixed feelings surrounding MDMA

In recent years, science has seen a revived interest in studying psychedelics and their potential therapeutic effects for various mental disorders.

There hasn’t been a new, effective drug meant to treat PTSD in nearly 20 years, but promising clinical trials performed since the previous decade have shown that MDMA may greatly enhance therapy.

Besides PTSD, research has found MDMA-assisted psychotherapy considerably reduces anxiety in autistic adults and terminally-ill cancer patients, as well as prevents alcoholism relapse.

Several small studies also suggest that the drug could address cases of clinical depression that intractable using conventional therapy. MDMA rapidly increases the availability of extracellular 5-hydroxytryptamine (5-HT) at the synapse, mirroring the action of commonly prescribed antidepressants.

Conventional antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), typically take about 6 weeks to produce optimal therapeutic change. MDMA, on the other hand, can offer instantaneous relief.

By this point, some ravers may be raising a single, incredulous eyebrow. If MDMA is such a fantastic mood regulator, what about the horrible comedowns?

After the MDMA high wears off, most users experience a 24- to 48-hour period during which they may feel lethargic, have a low appetite, or experience a state of unease or generalized dissatisfaction with life (dysphoria, or the opposite of euphoria). Colloquially, this unpleasant period is known as “suicide Tuesday”, a reference to the fact that the crash happens after a heavy weekend of partying.

Street vs pure MDMA may explain the ambivalent effects

Researchers at the Translational Psychedelic Research Program at the University of California, San Francisco monitored the mental state of eight men and six women diagnosed with alcohol use disorder as they completed an 8-week psychotherapy course.

Out of the ten psychotherapy sessions throughout this period, two involved the administration of MDMA. The participants initially received 125 mg of MDMA followed by a second dose of 62.5 mg of MDMA two hours later. This wasn’t your typical MDMA bought off the street from some shady drug dealer. This was clinical-grade MDMA, which is 99.98% pure.

Following these two MDMA sessions, during which they were counseled by professionals, the participants spent the night in the treatment center. After each such session, the patients’ mood was assessed once a day for a week.

Instead of a comedown, the participants actually had a positive mood overall with no significant fluctuations. What’s more, sleep quality improved following these MDMA sessions during a 3- and 6-month follow-up.

“The context drugs are taken in can play an important role in their risks,” study author Jacob Aday told PsyPost. “By using pure MDMA on a limited number of occasions, not combining it with other substances, getting proper nutrition, and taking it early enough in the day to still get adequate sleep, risks can be reduced — although not eliminated.”

The reported comedowns following illicit use of MDMA may be due to the sourcing of the drug and the specific environmental setting for recreational use.

Street-sourced MDMA is one of the most adulterated drugs on the market. Many times there might not be any MDMA at all. Drugmakers include other ingredients for a few reasons, whether to cut costs by bulking up their product with cheaper inactive ingredients or to achieve particular effects by adding other drugs to mask poor product quality or imitate the desired effect of the drug itself.

For instance, a 2004 study that analyzed the chemical makeup of ecstasy tablets seized by the police at raves found that 20% of the products had no MDMA whatsoever, while the rest had MDMA present in widely different dosages. Many tablets are diluted with all sorts of cutting agents — in some cases, horse tranquilizer or rat poison.

“The differences between clinical MDMA and recreational ecstasy are massive. An ecstasy tablet or a bag of crystal MDMA may contain anywhere between 0mg and 350mg of MDMA, plus any number of adulterants. In contrast, when we give MDMA clinically we use clinical-grade MDMA,” Dr. Ben Sessa, the co-author of the study and a research fellow at Imperial College, told VICE.

“People usually take recreational ecstasy at night. They stay up all night, missing out on sleep. This hugely contributes to feeling unwell and hungover the next day. The low mood effects persist for several days after missing a night’s sleep, which also causes this ‘Blue Monday’ effect a few days later.

“In contrast, we administer clinical MDMA at 9:AM, and the effects have worn off by the evening, at which point the patients feel back to baseline and naturally tired. They then get a good night’s sleep and do not have any immediate hangover effects in the following week.”

The researchers, however, caution that these findings shouldn’t be taken as evidence that MDMA comedowns don’t exist. They obviously do exist for the vast majority of people who aren’t careful and abuse the drug, and even for the drug in its pure form, these findings are only preliminary. Pure MDMA raises heart rate and blood pressure, so some patients with heart conditions may be at risk of cardiac arrest when taking the drug.

MDMA can be very dangerous once a safe dose is crossed, which is why it should only be procured from a trusted source. Self-medication with MDMA to treat one’s depression or anxiety is definitely a no-go.

The findings appeared in the Journal of Psychopharmacology.