Every time there's an airplane crash, somebody inevitably points out that driving a car is far more dangerous. Though death rates have fallen steadily in recent years, more than 30,000 people still died in motor vehicle accidents in 2013. That fact is by now a commonplace.

What is less well-known is that deaths from drug overdoses now far exceed that of car accidents. More than 46,000 people were killed by drugs in 2013. Most of these deaths were caused by prescription drugs, but for an increasing proportion heroin was the culprit — 8,200, to be exact. Most of these heroin deaths are chalked up to overdose in the media, but there are reasons to be suspicious of this characterization. Is it really simple overdose killing people?

For the most part, no. It turns out that most heroin deaths are probably not simple overdoses, but polydrug interactions, particularly between heroin and other nervous system depressants like benzodiazapines, tricyclic antidepressants, or alcohol. It's an important distinction both for addicts themselves and for crafting a drug policy focused on harm reduction.

What do we mean by overdose? This is when a drug user takes more than he or she can tolerate, and dies as a result. Heroin depresses the nervous system, so if you take too much, then you'll stop breathing and die. Simple.

The trouble with this story is that it is actually rather hard to overdose on simple heroin, particularly for experienced users. In fact, addicts are known to be capable of tolerating staggering quantities of pure heroin, dozens of times the average street dose in some experiments. It also usually takes several hours to die of a pure overdose, and treatment (with an opioid antagonist) is extremely simple — meaning that it ought to be pretty easy to save someone who has taken too much.

And complicating factors, the typical "overdose" fatality is typically not a naive heroin user — it's an older, long-term addict. (Though addicts who relapse after a period of sobriety — thus having lost their tolerance — are a significant minority.)

So if addicts are pretty resistant to overdoses, and the average heroin death is an experienced user, what gives? It turns out the answer is interactions with other drugs. Mixing heroin with other depressants is probably the most dangerous, because the effects do not combine linearly — instead, they reinforce and multiply each other. A small dose of heroin plus one beer may act as if they were a very large dose, plus a pint of vodka. A 2006 study found that roughly half of heroin deaths were also associated with alcohol.

This effect holds for all similar drugs — witness Heath Ledger, who was killed by a mixture of prescription opioids, benzodiazapines, and an anti-insomnia drug. As addiction scientists Shane Darke and Michael Farrell write:

What does kill heroin users is polydrug use. More specifically, the use of heroin with other central nervous system depressants, such as alcohol and the benzodiazepines. Death is due to respiratory depression, from the combined effects of these substances. While one of these may not kill if taken alone, together they are toxic. That’s why we see a large number of deaths with low morphine concentrations. [LiveScience]

However, mixing heroin with stimulants is also dangerous. Heroin and cocaine, for example (the infamous "speedball"), also strengthen each other's effects, risking an overdose. Worse, cocaine wears off much faster than heroin, so one can have a heroin overdose on board, and not realize it until the cocaine starts fading out — at which point it's often too late. Doubling up on both is even riskier — witness Philip Seymour Hoffman, killed by two different stimulants and two different depressants at the same time.

All this matters for some kind of sensible drug policy focused on harm reduction. In order for addicts to get clean and shape up their lives, they obviously need to not be killed by drug cocktails. Heroin by itself is a risky business, but the most immediate danger is in mixing it with other drugs.