Ecstasy damages the brain but also has toxic effects on muscles, according to new research at UCC. Dick Ahlstrom reports
Ecstasy is a constant risk to recreational users given its unpredictable impact on the brain and nervous system. Now researchers in Cork have discovered that the drug can also cause muscle tissue to dissolve.
"Ecstasy should be regarded as a toxic chemical and not as a recreational drug," says professor of medicine and biochemistry at University College Cork, Prof James Heffron. He has good reason for stating this given the effect it has on skeletal muscles.
He and colleague Prof Frank Lehmann-Horn at the University of Ulm have discovered that ecstasy can act on tissues outside the central nervous system. "It was said to have central effects only but we have shown it does also have effects in the periphery," says Heffron.
The drug, also known as MDMA, is very popular among young people attending clubs, but the synthetic amphetamine continues to cause unexpected and tragic deaths. It produces psychedelic and mood-changing effects by acting on the central nervous system but MDMA also triggers toxic reactions.
One of the most common, a rapid and difficult to control rise in body temperature, is the reason Heffron became involved in the research, which has been released on the internet by the Journal of Pharmacology and Experimental Therapeutics and will be published in the Journal next month.
"It came about because we were working on diseases that lead to high temperatures, particularly malignant hyperthermia," says Heffron. Malignant hyperthermia (MH) arises in rare cases when surgery patients react badly to anaesthesia. Their body temperature rises rapidly, and can cause death if not controlled.
"We thought that people who would be susceptible to MH, who have the gene for it, might be susceptible to death from ecstasy," he says. "It turned out that that was not the case," he says.
Yet one very valuable out-turn from the research was the team uncovered the drug's unexpected impact on voluntary muscle tissues. "We showed how ecstasy works in the body," says Heffron.
All of the symptoms linked to MDMA use including muscle contraction, pain and spasms and body temperature rise were thought to be linked to the drug's interaction with nervous system tissues. Heffron and Lehmann-Horn's work showed that the drug can also work outside the central nervous system, interacting with specialised receptor proteins on the surface of muscle cells known as nAChRs.
These are found at the junction between nerve and muscle tissues, the myoneural junction. The ecstasy or some component of it attaches to the receptors, switching on the muscle and over stimulating it.
"It triggers the muscle to go into contractions and leads to heat production," explains Heffron. "It leads to a breakdown of the muscle. It is literally breaking up the tissue, the tissue dissolves."
The muscle tissue can't take the sustained stimulation and begins to break down in a process known as rhabdomyolysis. This release of cell contents also leads to the severe toxic effects of the drug outside of the central nervous system. The kidneys for example are affected by this.
"There are well known renal effects," says Heffron. "That would probably be a consequence of the muscle breakdown. Material from the muscle tissue clogs up the filtering system of the kidney."
The situation for users may be complicated by the fact that street ecstasy pills usually contain a variety of other compounds including caffeine that may exaggerate the actions of ecstasy itself, Heffron adds.
Potential benefits from the research may be opportunities for an antidote to help those who react badly to the drug. It may be possible to develop a substance that can either block ecstasy from latching onto the nAChR receptor sites on the muscle or unseat them if they are already in place.