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Home Exclusive Psychopharmacology Psychedelic Drugs MDMA

New study suggests “comedowns” associated with MDMA are not a result of the drug itself

by Eric W. Dolan
April 22, 2022
in MDMA, Psychopharmacology
(Photo credit: DEA)

(Photo credit: DEA)

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The drug MDMA (3,4-methylenedioxymethamphetamine) might not produce depressive “comedowns” when used in a controlled clinical setting, according to new research published in the Journal of Psychopharmacology. The findings offer some initial evidence that declines in mood and cognition in the days following MDMA use are produced by factors related to recreational consumption, such as drug impurity.

MDMA, commonly known as “molly,” has shown promise in treating various mental health conditions when combined with psychotherapeutic interventions. But there are concerns about the after-effects of the drug, which have been widely reported by recreational users.

“Decreased mood or ‘comedowns’ have been commonly noted amongst recreational MDMA users. We hypothesized that these comedowns might be more related to the context that individuals take recreational MDMA in rather than due to MDMA itself,” said study author Jacob Aday, a postdoctoral scholar in the Translational Psychedelic Research Program at University of California, San Francisco.

“In other words, when people take ‘MDMA’ recreationally, it is often cut with other drugs by suppliers and combined with alcohol and other substances by users, dosages are highly variable, and it is regularly taken in nightlife settings where dehydration, overheating, and lack of sleep may lead to impairments in cognition and mood in the following days. When given in a clinical context these confounding variables can be controlled.”

The researchers analyzed data collected from 8 men and 6 women diagnosed with alcohol use disorder who had completed an 8-week psychotherapy course that included 10 sessions. During two extended psychotherapy sessions, the participants received 125 mg of MDMA followed by another dose of 62.5 mg of MDMA two hours later. Following these two dosing sessions, the participants remained in the treatment center overnight.

Mood was assessed once a day for seven days after each MDMA session. The participants maintained a positive mood overall and the researchers observed no significant fluctuations. “Instead of a comedown, participants actually maintained a positive mood in the days after dosing,” Aday told PsyPost. In addition, the patients were asked open-ended questions on non-dosing days, such as “How do you feel about MDMA-assisted sessions,” and responses the questions were generally positive.

The study also assessed sleep quality at baseline, during a 3-month follow up, and during a 6-month follow up. The researchers found that sleep quality tended to improve following the psychotherapy sessions. This is in line with other research, which has indicated that MDMA-assisted psychotherapy is linked to sleep improvements.

The findings highlight “that the context drugs are taken in can play an important role in their risks,” 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.”

But the researchers cautioned that the findings can only be considered preliminary at this point.

“There are several major caveats to keep in mind,” Aday explained. “The main being this was a small sample of 14 participants; however, we were mandated to use a small sample because these results were a part of an exploratory study of MDMA therapy for treating alcohol use disorder. The results were promising, so future studies with larger sample sizes are underway.”

“Additionally, because this was an exploratory study, it was open label with no control group, meaning participants knew they were going to get MDMA and not placebo. Because of this, we cannot rule expectation and placebo effects. Again, future research will build upon this work to address these questions.”

Even if MDMA does not produce transient declines in mood and cognition, the use of the substance still includes some risks. “Because MDMA raises heart rate and blood pressure while people are under the drug, those with heart conditions may be at increased risk for a cardiac event,” Aday said. “Additionally, individuals can be highly suggestible and vulnerable while under the influence of the drug, so it is important to take it in a safe context with trusted individuals.”

The study, “Debunking the myth of ‘Blue Mondays’: No evidence of affect drop after taking clinical MDMA“, was authored by Ben Sessa, Jacob S Aday, Steve O’Brien, H Valerie Curran, Fiona Measham, Laurie Higbed, and David J Nutt.

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