Friday, June 30, 2017

Solving the Heroin Overdose Mystery

How small doses can kill.

Heroin, like other opiates, depresses activity in the brain centre that controls breathing. Sometimes, this effect is so profound that the drug user dies, and becomes yet another overdose casualty. Some of these victims die because they took too much of the drug. Others die following self-administration of a dose that appears much too small to be lethal, but why? This is the heroin overdose mystery, and it has been known for more than half a century.

There was a heroin crisis in New York City in the 1960s, with overdose deaths increasing each year of the decade. There were almost 1,000 overdose victims in New York City in 1969, about as many as in 2015. The then chief medical examiner of New York, Milton Helpern, together with his deputy chief, Michael Baden, investigated these deaths. They discovered that many died, not from a true pharmacological overdose, but even when, on the day prior, the victim had administered a comparable dose with no ill effects. Helpern, Baden and colleagues noted that, while it is common for several users to take drugs from the same batch, only rarely does more than one user suffer a life-threatening reaction. They examined heroin packages and used syringes found near dead addicts, and tissue surrounding the sites of fatal injections, and found that victims typically self-administered a normal, usually non-fatal dose of heroin. In 1972, Helpern concluded that ‘there does not appear to be a quantitative correlation between the acute fulminating lethal effect and the amount of heroin taken’.

It was a science journalist, Edward Brecher, who first applied the term ‘overdose mystery’ when he evaluated Helpern’s data for Consumer Reports. Brecher concluded that ‘overdose’ was a misnomer. ‘These deaths are, if anything, associated with “underdose” rather than overdose,’ he wrote.

Subsequently, independent evaluations of heroin overdoses in New York City, Washington, DC, Detroit, and various cities in Germany and Hungary all confirmed the phenomenon – addicts often die after self-administering an amount of heroin that should not kill them.

Most scholarly articles concerning heroin overdose don’t mention the mystery; it is simply assumed that the victim died because he or she administered too much opiate. Even when the mystery is addressed, the explanations are wanting. For example, some have suggested that deaths seen after self-administration of a usually non-lethal dose of heroin result from an allergic-type reaction to additives, such as quinine, sometimes used to bulk up its street package. This interpretation has been discredited.

Others have noted that the effect of a small dose of heroin is greatly enhanced if the addict administers other depressant drugs (such as alcohol) with heroin. Although some cases of overdose can result from such drug interactions, many cases do not.

Some have suggested that the addict might overdose following a period of abstinence, either self-initiated or caused by imprisonment. Thus, tolerance that accumulated during a prolonged period of drug use, and which would be expected to protect the addict from the lethal effect of the drug, could dissipate during the drug-free period. If the addict goes back to his or her usual, pre-abstinence routine, the formerly well-tolerated dose could now be lethal.

But there are many demonstrations that opiate tolerance typically does notsubstantially dissipate merely with the passage of time. One piece of evidence comes from the addict’s hair, which carries a record of drug use. Many drugs, and drug metabolites, diffuse from the bloodstream into the growing hair shaft; thus, researchers can reconstruct this pharmacological record, including periods of abstinence, using ‘segmental hair analysis’. In a study that analysed the hair of 28 recently deceased heroin-overdose victims in Stockholm, there was no evidence that they had been abstinent prior to death.

A surprising solution to the overdose mystery has been provided by the testimony of addicts who overdosed, then survived to tell the tale. (Overdose is survivable if the antidote, an opiate antagonist, such as naloxone, is administered in a timely manner.) What do these survivors say was special about their experience? In independent studies, in New Jersey and in Spain, most overdose survivors said that they’d administered heroin in a novel or unusual environment – a place where they had not previously administered heroin.

by Shepard Siegel, Aeon | Read more:
Image: Bill Eppridge