MDMA has been shown to be neurotoxic or at least capable of triggering serotonergic dysfunction.  However, much of the research is based on high-dose animal studies where MDMA may behave differently and not in carefully administered human use. 

There are also political intentions coloring both sides of the debate, with pro and anti-drug supporters cherry picking data points and studies that back their desired outcomes in terms of legalization and popularization. 

And there is bad - or at least underpowered - science surrounding the topic.  Famously, George Ricaurte published a 2002 study claiming "severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA" that was later retracted after it was discovered the test subjects received methamphetamine instead of MDMA.  Wow.

Neurological risks from MDMA

Solid research hints that there are real risks to MDMA usage, including:

• Long term depletion in serotonin and 5-hydroxyindoleacetic acid (serotonin metabolite) depletion [Striatal serotonin is depleted in brain of a human MDMA (Ecstasy) user (2000), Plasma concentrations of 5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine in ecstasy users (2002)]
• Reduction in serotonin transporters (SERTs) [Loss of Serotonin Transporter Protein after MDMA and Other Ring-Substituted Amphetamines (2006)]
• Impaired cognition [Chronic cognitive impairment in users of 'ecstasy' and cannabis (2003)]
• But of course, every piece of research has an evil twin.  This well funded study NIDA study concluded "In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings-including our own-and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users."  

For more information on the biases and challenges with published studies, check out Dr. Peter Attia's series on "Studying Studies"

M Exploration Guide

Know what you're taking

Perhaps the number one risk is taking something other than M.  In no circumstance should you take something where you do not fully understand the source or have tested the substance yourself.  

At home test kits are growing in popularity and are recommended for any substance not procured through a physician.

Don't do too much

Dosing is dependent on your body mass and metabolism, but taking more than 250mg is too much.

Avoid stimulants

Research hints that toxic impacts can increase when M is combined with other stimulants such as amphetamines, cocaine, and even caffeine.

[The risky cocktail: what combination effects can we expect between ecstasy and other amphetamines? (2013), Caffeine enhances astroglia and microglia reactivity induced by 3,4-methylenedioxymethamphetamine ('ecstasy') in mouse brain (2010)]

Keep cool

Hyperthermia can increase the toxic effects of M.  Many settings are hot and crowded and dancing can exacerbate overheating.  

Stay salty

Hyponatremia is when your sodium levels reach dangerously low level.  Women may be more susceptible to these issues.  Excess water consumption can exacerbate this problem, so include sport drinks or sodium tables.

Space out your usage

Allow your body and brain time to recover between dosages.  Research suggests at least [2 weeks] between use.

Supplement smartly

Common supplements may reduce the harmful effects of MDMA through anti-oxidation, NMDA antagonism, and other mechanisms.  But not all supplements are created equal, so look for maximum quality, potency, and minimalism.  Browse neuroprotective supplements.