Why are tranquilisers addictive?

Researchers have discovered why tranquiliser agents are addictive.

Diazepam (valium) and temazepam are two commonly used examples of tranquilisers, which are also known as benzodiazepines. They're generally very safe, but patients can quickly become dependent upon them and suffer unpleasant withdrawal effects if they stop taking them.

The agents achieve their therapeutic effects, which include reducing anxiety and helping users to sleep, by sensitising the brain to one of its main inhibitory nerve transmitters, GABA. This damps down nerve activity, helping patients to feel calmer.

But now University of Geneva researcher Christian Lusher and his colleagues reveal in a paper in this week's Nature that the benzodiazepines also simultaneously activate the same addiction pathways as morphine and other opioids, explaining why users can get hooked.

By studying how the drugs affect nerve cell signalling in the brain, the researchers found that a side effect of the benzodiazepines is that they also switch off a population of nerve cells whose job it is to suppress the release of dopamine, the brain's pleasure chemical. This same group of cells is also deactivated by heroin-like drugs.

Consequently, in both cases, the levels of dopamine are boosted, generating desirable sensations of contentment, which reinforces the drug-taking behaviour and explains why users get hooked.

But there is some good news.

These addictive effects are all produced by just one subset of receptors for GABA, which contain a structure called the alpha-1 subunit. But the anxiety-busting effect of the tranquilisers is achieved by acting on a different receptor subset, which instead uses the alpha-2 subunit.

Armed with this knowledge it should now be possible for pharmaceutical companies to produce drugs with beneficial tranquiliser-like actions but which lack the addictive potential.