The gluco-regulatory effects of 3,4-Methylenedioxymethamphetamine (MDMA): A controlled n-of-2 self-experimentation

Background: Psychedelic drugs are increasingly being researched for their therapeutic properties in terms of treatment resistant mental illnesses. However, little is known about how they impact metabolism, which has implications for those with metabolic diseases such as diabetes. Hypohydration has been argued by some to cause glucose dysregulation, particularly due to elevations in arginine vasopressin (AVP). 3,4-Methylenedioxymethamphetamine (MDMA) is known to elevate AVP, resulting in body water retention. Thus MDMA offers a paradoxical state of elevated AVP and hyperhydration, allowing us to uncouple the effects of hydration state and hydration physiology on metabolism. Aims: This study aimed to test the impact of MDMA on gluco-regulation in a tightly controlled setting. Methods: Using a non-blinded AB study design, this self-experimentation involved two female scientists who underwent one day pre-trial within-person control of diet and activity. Both experimenters did the control (CON; no-intervention) arm first, followed by the treatment (MDMA) arm. Testing involved fasted measures pre- and post-MDMA (or equivalent timepoints during CON), then a 75 g oral glucose tolerance test, and a four hour follow up period. Blood samples, urine volume and specific gravity, body mass, and visual analogue scales were collected at set times throughout the testing period. Results: Relative to CON, MDMA resulted in gluco-dysregulation in both experimenters, particularly in relation to causing hyperinsulinaemia. However, plasma copeptin concentration (as a marker of AVP) only increased in one experimenter. For one experimenter, urine volume was greater during MDMA, with no distinct differences in specific gravity; for the other experimenter (with elevated copeptin concentrations), urine volume was lower with higher specific gravity. Visual analogue scales showed only the experimenter with high copeptin had increased thirst and xerostomia. Conclusion: Overall, MDMA may be implicated in gluco-dysregulation. Such a finding needs to be replicated in a larger sample, and in conditions that are similar to a therapeutic as per was estimated fitting a cubic spline using the function on 16 USA). Fasting insulin resistance was calculated using Homeostasis Model Assessment 2 University of UK). To minimize the chance of any experimenters being identifiable, an age range has been provided. were calculated by subtracting the MDMA value from the All and fully available by 2 self-experimentation showed MDMA induced higher plasma glucose variability and hyperinsulinaemia during fasting and after 75 g glucose ingestion, regardless of copeptin concentrations. The study raises questions regarding responders and non-responders of MDMA, and whether copeptin could be use to determine or understand these differences and potential risks. Further research needs to investigate the metabolic and gluco-regulatory effect of MDMA in a range of participants in circumstances that mimic therapeutic and recreational settings. Additionally, the mechanisms underlying MDMA-induced insulin resistance should be elucidated. Hopefully this small study gives a rationale for further investigation, by demonstrating glucose and insulin dysregulation under controlled physiological circumstances, and providing preliminary dietary recommendations to avoid ill-effects.