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Adverse effects of ecstasy to be studied by UA pharmacy researcher

The National Institute on Drug Abuse has awarded a researcher at The University of Arizona College of Pharmacy $1.7 million for a nearly five-year study of the long-term adverse effects of the street drug ecstasy.

Terrence J. Monks, PhD, head of the college's Department of Pharmacology and Toxicology, is a specialist in the study of drug toxicology, or the "bad" effects of drugs. He will be the principal investigator on the ecstasy project.

"Most research on ecstasy focuses on the pharmacological, or nontoxic effects of the drug," says Monks. "My interest lies in learning how the drug negatively affects the brain."

Classified as a Schedule I substance, ecstasy has been controlled in the United States since 1985. Ecstasy (also known as MDMA, or methylenedioxymethamphetamine) is a synthetic, psychoactive drug that is chemically similar to the stimulant methamphetamine. It produces an energizing effect as well as feelings of euphoria, emotional warmth, and distortions in time perception and tactile experiences.

These effects of MDMA have contributed to its popularity as a "party drug" among adolescents and young adults who frequent weekend-long "raves" or "techo-parties." However, the drug has a serious down side.

"A number of adverse effects are associated with the use of MDMA," says Monks. "MDMA use and abuse therefore has the potential to give rise to a major public health problem."

According to the U.S. Department of State, the short-term negative effects of ecstasy can be nausea, dilated pupils, dry mouth and throat, and lower jaw tension. Use of the drug often leads to dramatic increases in body temperature exceeding 100 degrees Fahrenheit, which in turn can lead to muscle breakdown and kidney and cardiovascular system failure. This hyperthermic response can therefore result in fatal blood clotting, heart attacks and strokes.

Scientific studies have found that ecstasy use also produces long-term damage to the brain's ability to release serotonin, which regulates mood, body temperature and memory.

"Ecstasy may be the only amphetamine-based drug that attacks the serotonin system," says Monks. "There is little doubt that it has the potential to be toxic to the human nervous system. The question is how."

Monks' research will focus on the process by which ecstasy is metabolized by the body. When the drug enters the body orally in pill form (the manner in which it is usually taken), enzymes in the body convert it either to harmless metabolites or into toxic metabolites. Predicting which people process ecstasy into toxic metabolites more readily than other people is the challenge.

"Individuals metabolize ecstasy differently," says Monks. "If 100 people take ecstasy, perhaps five will metabolize the drug very efficiently, whereas five others will metabolize the drug poorly. Since metabolism of ecstasy is required for it to produce neurotoxicity, the individual who efficiently metabolizes the drug will likely be more susceptible to the long-term adverse effects."

The UA professor is believed to be the only researcher in the U.S. studying the role of metabolism in the neurotoxicity of the drug.

The results of Monks' research will help people understand which individuals are more likely to suffer long-term negative effects of ecstasy.

"The multitude of adverse effects resulting from the misuse of ecstasy necessitates a complete understanding of the neuropharmacology and neurotoxicology of this unusual amphetamine derivative," says Monks. "We hope to help define important factors that contribute to individual susceptibility to the long-term adverse effects of this drug."

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