Article summary of The heroin overdose mystery by Siegel - 2016

What is the heroin overdose mystery?

The term overdose implies that someone has taken a dose too high, but many victims of overdose are actually self-administering addicts who took a dose which would not be expected to be fatal for them as they are drug-experienced and drug-tolerant. There is then not really a true pharmacological overdose of narcotics and it is yet a mystery as to why these people died.

What are the usual interpretations of overdose?

Different hypotheses have been proposed to explain these overdoses:

• The fatal reaction may be the result of the combined effects of heroin and other abused depressant drugs, because heroin addicts sometimes take other central nervous depressants as well (like alcohol and benzodiazepines).
• It may be an allergic or other type of reaction to contaminants, because heroin is often bulked up with various adulterants (like caffeine and sucrose).
• It may be an accidental overdose after a period of abstinence. The tolerance of prolonged drug use can have dissipated during the period of abstinence. 

Why should we look at the environment in which a drug is taken?

Research indicates that the majority of overdoses happen in new environments, an environment in which the drug user normally does not take the drug. Altering the context of drug administration increases drug-induced mortality.

How do acute and chronic tolerance protect the drug user from overdosing?

Acute tolerance refers to the decrease in the effect of a drug over the course of a single administration. Taking drugs disturbs the body in many ways (suppressing the cough reflex, respiratory depression, decreased pain sensitivity, etc.), but the body also detects these threats and starts homeostatic counter-responses. With repeated drug use, tolerance becomes enhanced and creates chronic tolerance. Rather than just responding reflexively to the drug, addicts show homeostatic compensations even when they just anticipate a drug.

How can Pavlovian conditioning explain accidental overdoses?

For repeated drug users, cues that are present at the time of taking the drug become conditional stimulus and the homeostatic drug-compensatory responses become the unconditional response. The drug-compensatory responses are elicited by drug-predictive cues and contribute to chronic tolerance and explain why an experienced addict can normally survive a high drug dose. When a drug is then taken in a new environment and some of the drug-predictive cues are not there, the conditional response is not initiated, chronic tolerance is not as high, and an addict can overdose.