Debunking the myth of ‘Blue Mondays’: No evidence of affect drop after taking clinical MDMA

This open-label study (n=14) study assessed the decline in mood and cognition, also known as ‘Blue Mondays,’ that are believed to occur following MDMA use. The study assessed these side effects in participants being treated with MDMA (125mg followed by a 62.5mg dose 2hrs later) for alcohol use disorder (AUD). It was found participants maintained a positive mood during the week following the dosing session and suggests that the ‘come downs’ associated with MDMA may be associated with illicit sourcing of the substance and recreational use.

Abstract

Background: Incorporating 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy has shown promise in recent years for treating various mental health conditions, particularly those involving trauma. However, concerns about declines in mood and cognition during the days following dosing, also known as ‘Blue Mondays’, have been raised as limitations to its clinical use. Although these changes have been well-documented among recreational users, there are critical confounds to these reports that limit generalizability to clinically administered MDMA.

Aims: Here, we aimed to evaluate the evidence basis for the negative side effects associated with MDMA as well as inform our understanding of the drug’s post-acute effects in a clinical context with an open-label study.

Methods: The current open-label study examined MDMA therapy for alcohol use disorder (AUD; N = 14) and measured mood, sleep quality, illicit MDMA consumption and anecdotal reports after the acute drug effects had worn off.

Results: Participants maintained a positive mood during the week following drug administration in a clinical context. Relative to baseline, self-reported sleep quality improved at the 3- and 6-month follow-ups. Finally, no participants reported using or desiring to use illicit MDMA, and the anecdotal reports indicated that they perceived the treatment favourably.

Conclusion: The results support the overall safety and tolerability of clinically administered MDMA and, importantly, suggest that the ‘come downs’ previously associated with the substance may be explained by confounds in research relating to the illicit sourcing of the drug and specific environmental setting for recreational consumption.

Authors: Ben Sessa, Jacob S. Aday, Steve O’Brien, H. Valerie Curran, Fiona Measham, Laurie Higbed & David Nutt

Notes

Many tend to associate the substance MDMA, also known as Ecstasy, with a decline in mood and cognition after the acute effects of the substance have worn off. In layman’s terms, these potential neurotoxic effects are widely known as ‘come downs’ and anecdotal reports from recreational users characterize these ‘come downs’ with a state of depressed mood a few days after MDMA use. Given that research is well underway into the therapeutic benefits of MDMA, unearthing the nature of these adverse effects is imperative for MDMA to become a viable therapy option for those in need.

The present paper explores these adverse reactions in the context of clinical research in which participants have been treated with MDMA. Furthermore, the paper seeks to delineate these effects in the clinical setting from reports of users self-administering MDMA in the recreational context. The paper at hand is part of a wider study in which 14 individuals with alcohol use disorder (AUD) were treated with MDMA-assisted therapy.

In the alcoholism study, participants received 10 psychotherapy sessions, with 125mg of MDMA being administered at sessions three & seven. A 62.5mg booster dose was also administered two hours following the initial dose in these sessions. While the wider study focused on the ability of MDMA-assisted therapy on alcohol consumption, the present paper focused on outcome measures related to post-acute mood and sleep quality as well as illicit MDMA use and anecdotal reports.

The main findings:

• Participants maintained a positive mood during the week after each MDMA session. This was measured each day following the two dosing sessions using the Profile of Mood States (POMS).
• The Pittsburgh Sleep Quality Index (PSQI) was administered at baseline, 3 months post-MDMA administration and 6 months post-MDMA administration to assess changes in sleep quality. Sleep quality was improved at the 3- and 6-month follow-ups relative to baseline measurements.
• No participants had any desire to illicitly use MDMA at 3-, 6- and 9-month follow-ups.
• Negative side effects, or come downs, may be explained by confounding variables associated with recreational use.

The results of the present study support the idea that the post-acute effects that have been associated with MDMA may not be relevant when this substance is administered in the clinical setting. Thus, this study further emphasizes the overall safety and tolerability of MDMA administered in the clinical context.

The anecdotal reports from recreational users may stem from the fact that MDMA is generally taken in nightlife settings in the UK (where this study took place) and post-acute may be explained by a combination of dehydration, overheating, exhaustion and sleep and dietary disruption from extended periods of dancing in crowded venues and the illicit sourcing and high dosing of MDMA.

Although the current study doesn’t help explain why ‘Blue Mondays’ do happen, it shows that within a controlled clinical setting, for those with alcoholism, it doesn’t happen. But, this study does contradict earlier finding by Matthias Liechti and colleagues (2001) that reported a third of participants having some depression of mood, lack of energy, and bad dreams in the days after MDMA dosing. A possible explanation for the difference posed by the authors is that in the earlier study there is no therapy given, another reason might be a reduced ‘after glow’ for those participants, wherein the present study new insights into their drinking behaviour could keep their mood elevated for the subsequent days.

This study is a secondary analysis of data from the first MDMA trial for alcoholism by Ben Sessa and colleagues earlier this year.

Summary of Debunking the myth of ‘Blue Mondays’: No evidence of affect drop after taking clinical MDMA