Mechanism and Pharmacokinetics

• MDMA (ecstasy, molly) is an amphetamine that releases endogenous catecholamines, and also has structural similarities to serotonin leading to inhibition of serotonin reuptake, with resultant mix of sympathomimetic and serotonergic effects.
  • Ingested orally, with peak effects within 2 hours and duration of effect 4-6 hours.
  • Tablet formulations vary widely, and severe toxicity may occur with as little as 1 tablet.

Signs and Symptoms

• Symptoms: increased alertness, euphoria, feelings of increased physical and mental abilities, blurry vision, anxiety.
• Physical exam: hypertension, tachycardia, dilated pupils, diaphoresis, bruxism, ataxia, agitation.

Toxicity

Most serious toxicities are related to hyperthermia, severe hyponatremia, and hepatotoxicity.

• Hyperthermia: results from a combination of adrenergic stimulation and exertion, serotonin syndrome, and atmospheric contribution (warm environment with patient’s decreased ability to dissipate heat). Can lead to rhabdomyolysis, DIC, and hepatic and renal failure.
• Hyponatremia: caused by both SIADH and by polydipsia; patients will drink large quantities of water in an attempt to stave off hyperthermia. Drop in sodium is often severe (<120) and may cause seizures, cerebral edema, brain herniation, and death.
• Hepatotoxicity: often a consequence of hyperthermia or DIC, though can be seen in absence of these complications as well. Clinical findings include abdominal pain, jaundice, vomiting. LFT abnormalities often present.
• Hypertension: similar to effects of other amphetamines and cocaine; usually responsive to benzodiazepines. Consequences include aortic dissection and intracerebral hemorrhage.
• Serotonin syndrome: can develop autonomic dysfunction, altered mental status, myoclonus, hyperreflexia, and tremors. Much higher risk in patients that are also using other serotonergic medications, including SSRIs, MAO-inhibitors, etc.

Evaluation

• Rule out other ingestions. There may be various adulterants in MDMA tablets.
• Rule out infection, thyrotoxicosis. History and context will usually be clear, but presentation of obtunded patient may be difficult to distinguish from sepsis, meningitis, metabolic cause if patient’s ingestion history is unknown.
• Check labs, especially sodium, creatinine, CK, LFTs, coagulation factors, fibrinogen, CBC, smear. Urine osmolality and electrolytes may help determine cause of hyponatremia (e.g., inappropriately high in patient with SIADH, low in compulsive water consumption).
• Urine toxicology will often screen positive for amphetamines, but a negative test should not be used to rule out MDMA intoxication in the right clinical setting.
• Obtain EKG and troponin, as MDMA use may lead to cardiac ischemia similar to other stimulants.

Management

• Decontamination: if airway is protected and overdose is suspected, consider activated charcoal 50g.
• Aggressively treat hyperthermia: see Drug-Induced Hyperthermia section. Consider intubation and paralysis if hyperthermia is severe, rapidly worsening, or refractory to initial treatment, or if there is evidence of end-organ damage.
• Benzodiazepines: treats psychomotor agitation, hypertension, seizures, and can be used as an adjunct to hyperthermia management. Avoid haloperidol as it may reduce seizure threshold, prolong QTc, and delay hyperthermia treatment.
• Hyponatremia: if mild, can treat with fluid restriction or saline, dependent on mechanism (see above); will usually resolve in 12-24 hours. Remember to avoid increases more than 6-8 per 24 hour period. Severe hyponatremia (<120) should be treated with 3% saline in consultation with nephrology, along with close monitoring in ICU setting.
• Serotonin syndrome: benzodiazepines are the mainstay of treatment. If the patient continues to display autonomic dysregulation and uncontrolled agitation despite benzodiazepine administration, consider cyproheptadine. Give 12mg as initial dose, followed by 2mg every 2 hours until clinical improvement.

Key Points

• MDMA intoxication is marked by mixed adrenergic and serotonergic toxidromes.
• Death most commonly results from hyperthermia; initiate aggressive cooling as soon as possible.

Devlin RA and Henry JA. Clinical review: major consequences of illicit drug consumption. Crit Care 2008; 12(1): 202-208.

Kalant H. The pharmacology and toxicity of “ecstasy” (MDMA) and related drugs. CMAJ 2001;165(7):917-28.