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Methylenedioxy-Methylamphetamine MDMA

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MDMA (3,4 – methylenedioxymethamphetamine), or more commonly known as Molly or Ecstasy, is a synthetic substance first developed in 1912 as a precursor to the synthesis of hemostatic agents (not as an appetite suppressant as incorrectly reported).  Due to its effects on promoting empathy and facilitating communication, the drug became popular in the early 1970s among psychiatrists for its therapeutic potential.  The drug would later find heavy use in dance parties and festivals as it became prominently associated with rave culture due to its heightened euphoric effects.  The DEA subsequently classified it as a schedule 1 drug in 1985 as the potential for harm and abuse was recognized.  To this day, ecstasy continues to be used by millions.  Its effects on the cardiovascular, neurologic, renal, and hepatic systems can be devastating, and recognition of its toxicity is essential to medical providers.

Etiology

The potential for MDMA toxicity exists with every ingestion.  MDMA is commonly ingested orally through tablet form; however, the powder itself can be snorted.  Recreational doses of the drug can vary significantly.  During the 1990s and early 2000s, doses ranged between 73 mg to 103 mg while doses have also been reported to be as low as 50 mg to as high as 150 mg per tablet.  Analysis of compounds sold as Ecstasy/Molly has also revealed variability of composition with other substances aside from MDMA which include MDEA, MDA, ephedrine, ketamine, paracetamol, and other substitutes – some of which are inactive and others which may have profound hemodynamic effects.  As a result, significant adverse effects and toxicity can occur with a one time or first-time ingestion due to the random dosage and composition of the drug.

Ecstasy is also often taken with other illicit drugs which can potentially lead to a compounding of each drug’s individual effects on the neurologic and cardiovascular system.  This compounding effect in combination with physical activity in a hot, humid environment such as a rave can lead to significant hyperthermia and dehydration

Epidemiology

Trends in MDMA use have been well documented throughout the years with user age ranging from the 8th grade all the way to the college level and adulthood.  Review of epidemiological data revealed a significant increase in usage between the 1990s to early 2000s.  For example, lifetime ecstasy use on one college campus was found to increase from 16% to 24% between the years 1986 to 1990 while a national sample of college students saw a 69% increase between the years 1997 to 1999.  From 1999 to 2000, lifetime use among 8th graders increased from 2.7% to 4.3% while this increase was significantly more in 12th graders (8% to 11%).  Also, emergency room visits in the United States were also found to increase from 253 to 4511 between 1994 and 2000.  A 2002 “Monitoring the Future” study, found 12.7% of United States college students having used ecstasy once in their lifetime.  The 2002 National Survey of Drug Use and Health found a greater than 200% increase in ecstasy use by 18 to 25-year-olds from 1996 to 2002.

While the number of users increased significantly from the early 1990s and 2000s, the number of new users was variable from the period of 2002 to 2007.  Surveys found a decrease in users from 1.2 million in 2002 down to 642000 in 2003 then up to 860000 from 2006 to 2007.  2011 data from the National Survey on Drug Use and Health estimated about 14.5 million users aged 12 or older had used ecstasy at least once in their lifetime with approximately 900000 using it for the first time in 2011.  This number increased to 17 million in 2013 with the highest use among individuals aged 18 to 25 years. Though MDMA still falls behind cannabis, opioids, and other amphetamine use in the United States and worldwide, it remains a significant public health concern due to its adverse effect profile.

Treatment / Management

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.

Differential Diagnosis

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