Central Basis For MDMA (ecstasy) Induced Hyponatremia

Clinical studies have shown that hyponatremia can be induced by the ingestion of the recreational drug MDMA (3,4-Methyl​enedioxy​methamphetamine, ecstasy) when combined with a water intake (Baggot et al., 2016). However, the mechanisms by which MDMA induces hyponatremia is unknown. Hyponatremia is a life-threatening condition that causes rapid swelling of the brain and is commonly encountered in critical care medicine (emergency) (Woods et al., 1993 & Kirch, Bigelow, Weinberger, 1985). Under the Controlled Drugs and Substances Act (CDSA), MDMA is a schedule 1 drug (illegal) and consumption usually occurs at dance parties or raves. Nonetheless, despite MDMA’s scheduling, the Multidisciplinary Association for Psychedelic Studies (MAPS) has headed the movement toward using MDMA for assisted psychotherapy for PTSD (Sessa, Higbed, & Nutt, 2019). In summary, with a prevalence of 3.5% of young adults 18-25 years old using MDMA in the United States in 2014 (Betzler, Viohl, & Romanczuk-Seiferth, 2017), along with the mainstream marketing of MDMA for PTSD, combined with very serious and potentially deathly side effects makes this substance worthwhile to investigate. Findings could not only aid in MDMA associated hyponatremia but could also provide the foundation clinically for fluid regulation during MDMA assisted psychotherapy. Clinically, ingestion of MDMA has been shown to cause an increase in the hormones vasopressin and oxytocin (Wolf et al., 2006). Therefore, we examined cFos activity in male rats, we show that there is an increase in both cFos activation of vasopressin as well as oxytocin neurons of the supra optic nucleus. Next, we wanted to test the notion that MDMA causes an increase in thirst. Our data shows that an injection of MDMA does not increase drinking behavior. Combatting the conventional thinking that MDMA causes an increase in thirst. Interestingly, in line with the human literature, when you combine MDMA with a gastric water load, it is sufficient to drop serum sodium levels to hyponatremic levels i.e. <135mmol/L. Indicating that a water load combined with MDMA is necessary for MDMA induced hyponatremia. Conventionally, MDMA has been shown to increase the amount of serotonin within the synaptic cleft, via the inhibition of uptake via the serotonin transporter (Oeri, 2021). To determine if MDMA is working via the release of 5HT in a temperature-controlled environment we utilized whole cell patch clamp slice electrophysiology of male double transgenic Wistar rats enabling fluorescent identification of vasopressin and oxytocin neurons. Interestingly, at a bath temperature of a constant 30°C, a bath application of 5HT was sufficient in causing an enhancement of action potential firing, and this could be blocked by a 5HT receptor antagonist. Moreover, a bath application of MDMA also caused an increase in action potential firing, which too could be blocked by a 5HT receptor antagonist. CIHR. HBHL, McGill Faculty of Medicine This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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