Originally published in The Ottawa Citizen April4, 2005

First of two parts

Recently, one of my patients with bipolar disorder took Ecstasy at a rave. Within 60 minutes she had collapsed on the dance floor from dehydration.

After a thorough assessment in the emergency room, she was given intravenous fluid replacement and sent home. The following day she came to my office for a follow-up visit, experiencing a precipitous decline in her mood.

This two-part series will look at four commonly used club drugs: Ecstasy (3,4-methylenedioxymethamphetamine or MDMA), GHB (gamma-hydroxybutyrate), Rohypnol or the date-rape drug (flunitrazepam), and ketamine. How do these drugs work and what are the health risks?

The club drugs stimulate the release of the neurotransmitters serotonin, norepinephrine and dopamine from brain cells. These neurotransmitters are intimately involved with mood stability. People use club drugs to enhance social interaction: They feel less inhibited and experience increased empathy, physical closeness and euphoria.

MDMA is the drug of choice at a majority of raves. It is an amphetamine derivative originally developed in 1914 for use as an appetite suppressant, but it never got past animal testing. Its chemical structure is similar to the hallucinogen mescaline. MDMA is addictive but less so than amphetamine, and it does not cause psychosis as often as LSD or other hallucinogens.

Many of the illicitly manufactured MDMA tablets are not pharmaceutical grade. They can contain “binders” or extra ingredients such as caffeine, dextromethorphan (cough suppressant), pseudoephedrine (decongestant), or hallucinogens like LSD or other potent amphetamine derivatives. The latter two ingredients in combination with MDMA can have strong unpleasant hallucinogenic effects.

MDMA’s effects occur 30 to 60 minutes after ingestion, faster if it is crushed or if its powder form is snorted. The effects can last up to eight hours. Serotonin, dopamine and norepinephrine flood the synapses or spaces between the nerve cells. This effect is enhanced by MDMA’s ability to block a brain enzyme that breaks down these neurotransmitters.

The euphoria occurs after a brief feeling of agitation, time disorientation, lack of appetite and reduced thirst. Some people may experience a mildly locked jaw (trismus) or will grind their teeth (bruxism). Both of these side effects can be tempered by sucking on a lollipop.

The overstimulation of the brain and central nervous system can lead to a serious life-threatening condition. The heart rate and blood pressure can increase above acceptable limits. Some users will experience tremors, seizures, clinically significant irregular heart beat (arrythmias), parkinsonism, esophoria (the eyes turn inward — cross-eyed) and an inability to urinate (urinary retention).

The most serious side effect of MDMA ingestion is an elevated core body temperature (hyperthermia) due to serotonin syndrome. This syndrome can lead to muscle rigidity and seizures, muscle breakdown (rhabdomyolysis), acute kidney and liver failure, adult respiratory distress syndrome, and blood clotting abnormalities.

MDMA also stimulates the pituitary gland in the brain to release antidiuretic hormone (ADH). This hormone will reduce the kidneys’ ability to produce urine in response to an increased fluid load; they cannot excrete water into the bladder.

This creates a ‘perfect storm’ of pathology. The body overheats from dancing and the effects of the drug. The kidneys shut down. The user will dramatically increase his or her intake of water and other fluids in response to increased body temperature. Without the kidney’s ability to excrete water, the fluid overload reduces the blood sodium concentration (hyponatremia) through dilution. Low sodium concentration levels coupled with high body temperatures can cause confusion, delirium, paranoia, headache, anorexia, depression, insomnia, irritability, and a rapid, involuntary, oscillatory motion of the eyeball (nystagmus), all of which may continue for several weeks.

Several days after using ecstasy, the effects of serotonin depletion can cause depression, and for some it is severe. People who repeatedly use MDMA increase their risk of cognitive deficits and potentially permanent memory impairment.

MDMA does change the brain’s normal function. Indeed, studies indicate that long-term use in typical recreational doses can lead to a paranoid psychosis that cannot in practice be distinguished from schizophrenia. Prolonged drug abstention will lead to a reversal of the psychosis.

There are some animal and human studies that indicate that MDMA use (possibly in conjunction with cannabis) can lead to cognitive decline in otherwise healthy young people.

My patient with bipolar disorder experienced a precipitous decline in mood because the MDMA depleted the serotonin stores in her brain. People with mental illness are more vulnerable to the deleterious effects of MDMA and other club drugs. It is akin to a patient with asthma or chronic lung disease who smokes. They will tend to have more severe disease and attacks than someone who does not smoke.

These drugs are adulterated with other chemical additives and, although most club drugs look like prescription medicines, they are illegally made and can cause harm even in small doses.

I will return to the club in my next column to review GHB, Rohypnol and ketamine.

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© Dr. Barry Dworkin 2005