Grant: Catalyst Grant: Prevention and Treatment of Illicit Substance Use

Ecstasy is a widely abused drug that is becoming increasingly popular with young people who find the effects of the drug pleasurable. Recent news reports have highlighted the number of deaths of under sixteen year old minors associated with the taking of Ecstasy. Unfortunately Ecstasy tablets contain more than one active ingredient and these ingredients (usually 3-4-methelenedioxymethamphetamine combined with one of a group of compounds called piperazines) can act synergistically in the brain to release substances known as the monoamines. These piperazine drugs are a relatively new additive to Ecstacy tablets hence there has been little scientific study of their harmful effects. Furthermore, we know little about the combined adverse effects of piperazines with 3-4-methelenedioxymethamphetamine. While the Ecstasy-induced increases in monoamines are associated with heightened pleasure they can also cause serious unwanted side effects that can lead to death. One monoamine known as serotonin is associated with "serotonin syndrome" which involves a critical increase in body temperature that rapidly leads to multiple organ failure. Accumulating evidence indicates that the other monoamines released in the brain, namely noradrenaline and dopamine, following ingestion of Ecstasy also play a role in the serotonin syndrome. By blocking the sites that these monoamines act on with specific drugs, we believe we may alleviate the serotonin syndrome. This research will examine the effects of the component drugs found in modern day street Ecstasy using a rat model whereby we monitor the release and turnover of monoamines in the brain and monitor blood levels of Ecstasy and the relevant piperazines. We can also monitor the behaviour and body temperature of the rat and induce the serotonin syndrome. We will investigate drugs that act to block the sites for monoamines as potential treatments for the serotonin syndrome, which in turn may prove useful in the clinical setting.