MDMA is absorbed via the GI tract with an onset of effect between 20 minutes and 1 hour after consumption.  Peak concentrations occur 2 hours after oral ingestion, and it is broken down in the liver by the enzyme CYP2D6.  MDMA has a half-life of about 8 hours taking approximately 40 hours to clear 95% of the drug from the body.  Thus, continued effects of the drug will continue to linger for several hours after ingestion.[6][17][18]

Presentation of MDMA toxicity is variable due to the common practice of co-ingestion with other illicit substances.  Even self-reported mono-ingestion of Ecstasy/Molly is not reliable due to the varying composition of the synthesized drug.  Patients may present tachycardic, hypertensive, hyperthermic, and agitated.  Adverse effects, even at minor recreational doses, include increased muscle activity (such as bruxism, restless legs, and jaw clenching), hyperactivity, insomnia, difficulty concentrating and feelings of restlessness.[14]  The sympathomimetic properties in MDMA overdose can lead to severe toxicity manifesting as cardiovascular, neurologic, hepatic, and electrolyte disturbances. Significant elevations in both heart rate and blood pressure have led to reports of life-threatening cardiac dysrhythmias, myocardial infarction, aortic dissection, and intracranial hemorrhages.[8][19][20]  Because MDMA undergoes hepatic metabolism via cytochrome P450, severe hepatoxicity can occur leading to fulminant liver failure.[21]  CNS hyperactivity can lead to delirium and seizures.[22]  Elevated levels of serotonin can result in serotonin syndrome, and patients may present with hyperpyrexia and myoclonus.[23] 

Because Ecstasy is a popular rave drug, the dangerous combination of intense physical activity (such as dancing) along with the heightened sympathomimetic effects of the drug lead to an increase in body temperature that resembles heat stroke and resulting in rhabdomyolysis.[24] Significant increases in fluid consumption by users in such a setting coupled with elevated levels of vasopressin have potentially contributed to the development of cerebral edema, seizures, and death.[25][26]

• Obtain finger stick for blood sugar levels
• Chemistry for sodium levels and other electrolyte abnormalities such as hyper or hypokalemia
• Urine, potassium, BUN/Cr, CK levels and myoglobin levels for the evaluation of rhabdomyolysis and renal injury
• LFTs for hepatoxicity
• Aspirin, alcohol, acetaminophen levels, and urine drug screening
• EKG
• Head CT, LP may be necessary for the undifferentiated altered and febrile patient

Emphasis should be on maintaining airway along with stabilization of breathing and circulation.  Patients may present obtunded due to hyponatremia requiring endotracheal intubation.  Though no formal contraindication to specific RSI agents exists, caution can be taken with ketamine which could potentiate the hyperadrenergic state of the already hypertensive and tachycardic patient.  If rhabdomyolysis is a consideration, avoiding succinylcholine due to hyperkalemia should be considered in favor of rocuronium or vecuronium.  Patients who present in severe toxicity within one hour of ingestion can receive activated charcoal PO or via an NG tube.  Agitation should be controlled with benzodiazepines such as lorazepam or diazepam.  For the hyperthermic patient, evaporative cooling along with ice packs to the groin and axilla are beneficial.  More invasive measures may be necessary in extreme cases.  If treatment fails, dantrolene is a consideration.  Antipyretics, such as acetaminophen, have no role and can worsen an already compromised liver. 

Patients in MDMA toxicity can present with seizures and hyponatremia.  Those with seizures should receive benzodiazepines.  If hyponatremia is the cause, patients should be free water restricted and treated with hypertonic saline.  Urine output should be closely monitored with a foley.  Caution is necessary with the judicious administration of IV fluids.

The undifferentiated tachycardic, hypertensive, hyperthermic, and altered patient, necessitates a broad approach to treatment and evaluation since this constellation of findings is not specific to MDMA toxicity.  Hence, patients may require a head CT, LP, and coverage with broad-spectrum antibiotics.[27]

• Anticholinergic toxicity
• Cholinergic toxicity
• Neuroleptic malignant syndrome
• Malignant hyperthermia
• Serotonin syndrome
• MAOI inhibitor toxicity
• Meningitis/encephalitis
• Heat stroke/exhaustion
• Rhabdomyolysis
• Amphetamine toxicity
• Cocaine toxicity

The two most frequently reported causes of death include hyperthermia and hyponatremia.  While toxicity can be severe, review of the literature reveals deaths related to MDMA toxicity to be rare.  Confounding factors in some reports are that other drugs were co-ingested thus making it difficult to find MDMA as the sole cause of death.  One study found that in the 10 years to 2006, ecstasy-related deaths numbered approximately 50 per year though were not purely ecstasy-related.  When it was the sole drug implicated, this number dropped to 10 per year.  A retrospective case review of ED admissions related to ecstasy revealed a death rate of 0 to 2%. [28]  It is worth noting that these conclusions were level III evidence-based. 

Though deaths are rare, the potential for long term side effects has been demonstrated through animal and radiological studies.  Serotonin plays a role in emotion, memory, and high order cognitive processes.  Previous animal studies revealed a loss of serotonin axon terminal markers.  These losses were found to be extremely long lasting in MDMA-treated monkeys.  PET scans in baboons showed significant decreases in radioactivity levels in variable areas of the brain.  Human volunteers with a history of MDMA use underwent PET scanning and were found to have a global dose-related reduction in a structural element of serotonin.  Further studies of PET scans in volunteers with a history of MDMA abuse yielded similar findings however with additional alterations to the amygdala and areas of the neocortex.  Deficits in short term memory,  visual memory, and verbal memory and reasoning seem to be associated.  Cerebrovascular systems may also be affected which may manifest down the line as a decline in cognitive potential akin to dementia.[29][30]

Neurologic complications include delirium, seizures.[22]

Cardiovascular complications include cardiac dysrhythmias, myocardial infarction, aortic dissection, and intracranial hemorrhages.[8][19][20]

GI complications include severe hepatotoxicity which can lead to fulminant liver failure.[21]

Renal complications include rhabdomyolysis and acute renal failure.[24]

Endocrine complications include SIADH resulting in life-threatening hyponatremia.  Patients can also present with hyperpyrexia mimicking heat stroke.[24][25][26]

Minor complications include increased muscle activity (such as bruxism, restless legs, and jaw clenching), hyperactivity, insomnia, difficulty concentrating and feelings of restlessness.[14]

MDMA toxicity can be life-threatening and involve multiple organ system dysfunctions necessitating the need for an interprofessional approach.  It is important, thus, for providers to be aware of the potential toxicities that may arise and be ready to treat aggressively as treatment is mainly supportive. 

Ultimately, the primary remedy to the problem is prevention.  Peters and Kok performed a literature review to identify reasons for ecstasy use and found reasons varied widely from curiosity, to achieve the same level of intoxication as friends, availability/pricing, enhance mood and social interaction, and social influence.[31]  The myth that Molly is safer because it is pure MDMA also does not aid in preventing its use.  Further education among youth and young adolescents to the toxic potential of MDMA is essential to blunting its continued use.