Why shouldn't you take heroin and alcohol together?

Um, because you shouldn't take heroin in the first place! No, don't worry, I know what you meant by this question. Heroin and alcohol together make a lethal cocktail, and there's a reason for that.

How does heroin work? The body makes opiates by itself, all the time, and this is the reason substances like morphine and heroin work in the first place: the body actually has receptors ready and waiting for them. When some of the body's own opiates (called endorphins) bind to to their receptor, the result is a decrease in the output of GABA from the brain's neurones. As you might know, GABA is the major inhibitory neurotransmitter present in the brain, and so the net result of this is that other neurones, free from GABA inhibition, get activated (they become more likely to fire). Some of these hyped-up neurones secrete dopamine, a substance intimately involved in the reward pathways of our brains. This might be why you get a "high" after during stressful exercise, nice food, or orgasm - all conditions in which endorphins are released.

Heroin mimicks our natural endorphins, and this accounts for the "rush" that you get from heroin, and its addictive nature. The above pathway might sound a little complicated, but that's not my fault - it's the way we're wired up! The image to the right (click on it to enlarge) depicts the story graphically; it's from www.cnsforum.com.

When it comes to respiration, however, the effects of morphine/heroin are slightly different. They switch off a different set of cells, such that the GABAergic inhibition of respiration is increased rather than decreased. By itself this effect is only moderately potent (you can safely administer therapeutic doses of morphine to healthy people without stopping their breathing, although you will usually slow their respiration somewhat).

If respiration can be said to be inhibited by GABA, it is excited by another neurotransmitter, glutamate. Usually these forces are controlled by the respiratory centre so that they are in balance - if you need to breathe a little faster, up the glutamate; to decrease respiration, up the GABA. If you've taken heroin though, your GABA neurones are already firing too quickly, slowing your rate of breathing down. Add alcohol to this volatile situation, and you breathing might well stop. Why? Alcohol is a central nervous system depressant, and it works in two ways:

• it interacts with GABA receptors in such a way that it increases GABA's inhibitory effects
• it binds to glutamate receptors, preventing glutamate from binding and doing its (stimulatory) job

Needless to say, alcohol also therefore causes respiratory depression. Add the two together, therefore, and you may have a lethal cocktail.

In summary:

• Heroin mimicks the body's endorphins (only more strongly), and its binding indirectly increases dopamine release (accounting for the "high" and its addictive properties) and well as enhances the GABA inhibitory signal to the respiratory centre.
• Alcohol increases the effects of GABA, and decreases the effects of the excitatory neurotranmitter glutamate.
• Together the drugs are synergistic and may lethally depress one's respiration.