03-30-07 Why the Agony About Ecstasy

Why the Agony about Ecstasy?

One percent of the population uses Ecstasy once a month. Twenty four percent of college students use this drug regularly. The majority of 16 year-olds believes Ecstasy (Adam, XTC, M&M, E) use is “safe”.

Ecstasy (MDMA-3, 4-methylenedioxymethamphetamine) is one of the “Designer Drugs” of the 1980s.  The term “Designer Drug” was first used by a Californian pharmacologist to describe the private synthesis of drugs differing from the parent compound which rendered them immune from the DEA.  The loophole was that until a drug was isolated, studied, and scheduled, no laws could apply to it.  The Controlled Substance Analogue Enforcement Act of 1985 categorized analogs of controlled substances as Schedule I and all the laws of Schedule I subsequently applied to them.

MDMA has the same basic chemical structure as an endogenous catecholamine (as do ephedrine and amphetamine).  It alters mood and perception, increases energy and empathy.  It is one of a group of drugs called enactogens (meaning to touch within) and is it initiates euphoria, “inner peace” and a desire to socialize. MDMA has all the right characteristics for a dance drug and is popular at raves (dances).  The aftermath of Ecstasy is a day of drowsiness, myalgia, fatigue, and depression- frequently called “Terrible Tuesday”.

Serotonergic neurons lie next to midline nuclei of the brainstem and project to virtually all areas of the brain.  Serotonin effects mood, personality, affect, appetite, motor function, temperature regulation, sexual activity, pain perception, and sleep. Serotonin is also produced in the enterochromaffin cells of the intestine and, when released, contributes to peristalsis.  Platelets take up serotonin and it is released to interact with other platelets and vascular smooth muscle.

The main mechanism of action of MDMA is release of serotonin from serotonergic neurons which causes depletion of central serotonin stores. The number of serotonin reuptake transporters is also decreased.  The drug also causes irreversible inhibition of the enzyme tryptophan hydroxylase (which is rate limiting step in synthesis of serotonin).  The enzyme is inhibited up to 2 weeks as the enzyme must be resynthesized.   

Tryptophan→/→/→/→5HTP→→→→  5HT (serotonin)               

                 Tryptophan

                 hydroxylase

                (Inhibited by MDMA)                                     ↓↓↓

                                                           

                                                                                5-HIAA (urine)

5-hydroxyindoleacetic acid

Usual dose is 100 mg MDMA per tablet but tablets can vary from 50 mg to 250mg.  Onset of action is within 30 minutes and peak serum levels occur at 1-3 hours.  Toxic dose is extremely variable.

In overdose, this drug is similar to an amphetamine (or stimulant) overdose and heart rate, blood pressure and temperature are increased.  The person is diaphoretic, agitated, and may have muscular rigidity.  Hyperthermia can be severe and is frequently the cause of death. Rhabdomyolysis may occur.  Hyponetremia from SIADH production has been reported.  Treatment is supportive.  Hyperthermia should be addressed as soon as possible.  Dantrolene may be a consideration, although evidence is inconsistent. 

A major concern with MDMA is the long-term effects on cognition. One of the reasons that animal research was discontinued with this drug was that it caused neurodegeneration of CNS serotonin axons.  Once the axon degenerated, different patterns of recovery occurred in different areas of the brain i.e., some areas had no axonal regeneration and other areas had increased density of axonal regeneration.  The clinical implications of this axonal degeneration and recovery are unknown.

Memory loss and other cognitive deficits were seen in MDMA users even 6 months after abstinence.  PET studies of users are abnormal.

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

Donna Seger, MD

Medical Director

Tennessee Poison Center

Website: www.tnpoisoncenter.org