Michael Jackson

Michael Jackson

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

Regardless of the final legal outcomes, it is sad that Michael Jackson was killed by inappropriate use of sedative drugs.  The ruling that his death was a homicide is suggestive of negligence and perhaps poor understanding of how drugs work.

It seems that MJ was taking a number of different drugs to help with his sleeping problems.  His doctor was using lorazepam and midazolam in addition to propofol to help MJ sleep but he was finding that each drug alone or in combination was not producing the desired results.  Lorazepan and midazolam are both Valium like drugs that can be used as anti-anxiety and sedative drugs.  They can be taken in pill form so the safety factor in terms of an overdose is reasonably good.  It is difficult to overdose accidentally.  Propofol can only be administered intravenously, so the risk for an accidental overdose is much greater with this drug.

A pharmacology lesson comes from a discussion of how these drugs work on the brain to produce their sedative effect.  All of these drugs act at receptors for the neurotransmitter GABA. GABA, lorazepam, midazolam and propofol all act to turn off or inhibit neuronal activity.  When we are talking about neurons in the parts of the brain that are responsible for anxiety, this is good as that is where these drugs produce their sedative actions.  However, when the neurons that control breathing or the heart beat are affected that is where an overdose becomes an issue.

It looks like drug tolerance may have played a big role in what happened to MJ.  His physician was administering lorazepam, midazolam and propofol but finding that they were not working well.  This is because each drug acts at the same site and the brain adapts to the continued presence of the drug.  The drugs become less effective over time and more and more drug is required to get to the same therapeutic effect.  As higher and higher doses are given, an overdose becomes more and more likely.

A beneficial strategy would be to use a sedative drug or drugs that act through mechanisms that are different from those used by lorazepam, midazolam and propofol.  There would be no tolerance to the new drugs and lower and safer dose could be used.  Knowledge of this basic pharmacological principle might have reduced the overdose risk for the King of Pop.