Fluid Restriction May Prevent MDMA-Related Hyponatremia

TOPLINE:

The high incidence of acute hyponatremia after the administration of a single dose of 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy, in healthy individuals may be mediated by oxytocin rather than vasopressin and can be reduced with fluid restriction.

METHODOLOGY:

• MDMA is being studied as a potential treatment for posttraumatic stress disorder; however, even a single dose of this medication can cause acute hyponatremia, a condition characterized by low levels of sodium in the blood.
• Researchers conducted a secondary analysis of four randomized, placebo-controlled, double-blind, crossover clinical trials to examine the incidence and severity of hyponatremia after a single MDMA dose (100 mg or 125 mg) in healthy participants with no somatic or psychological illnesses.
• Measurements were taken of plasma oxytocin, copeptin, and sodium levels repeatedly within 360 minutes after MDMA intake, with the peak MDMA concentration expected at 180 minutes.
• The incidence and severity of hyponatremia were assessed within 360 minutes after a single dose of MDMA; the effects of fluid restriction on plasma sodium levels and MDMA’s impact on plasma oxytocin or copeptin levels at 180 minutes were also analyzed.

TAKEAWAY:

• Overall, 96 participants (mean age, 29 years; 35% women) received single oral doses of 100 mg (41%) or 125 mg (59%) MDMA, with fluid intake restricted in 15 participants and unrestricted in 81 participants.
• Hyponatremia occurred in 31% of participants, with the decrease in plasma sodium levels at 180 minutes after MDMA administration more pronounced in those receiving higher doses (P = .045).
• Fluid restriction demonstrated significant protective effects, as none of the participants in the fluid-restricted group experienced hyponatremia, in contrast to 37% of those in the fluid-unrestricted group (P = .002).
• Plasma oxytocin levels increased dramatically by 433% at 180 minutes, whereas copeptin levels decreased slightly by 0.8 pmol/L.
• In participants with restricted fluid intake, changes in plasma sodium levels showed a negative correlation with changes in oxytocin (correlation coefficient [R], −0.4; P P 

IN PRACTICE:

“These findings suggest that fluid intake should be restricted when MDMA is used in therapeutic settings, such as in MDMA-assisted therapy for posttraumatic stress disorder,” the authors wrote.

SOURCE:

The study was led by Cihan Atila, MD, PhD, Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland. It was published online in JAMA Network Open.

LIMITATIONS:

The study had a small sample size in the fluid restriction group and sex imbalance between groups. Additionally, only single doses of MDMA were used without any placebo control assessment. The total amount of fluid intake and intravenous saline application was also only recorded in patients performing fluid restriction.

DISCLOSURES:

The study received support from a grant by the Swiss National Science Foundation and research grants from the Swiss Academy of Medical Sciences and Gottfried and Julia Bangerter-Rhyner Foundation. Two authors reported receiving research grants and/or serving as consultants for separate institutions and companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.