Pharmacologic aspects of benzodiazepine tolerance and dependence

Benzodiazepines, which are among the safest and most effective drugs, possess all the characteristic of abuseable compounds. Although there appear to be differences in potency among compounds and variations in sensitivity among individuals, benzodiazepines have clear reinforcing properties. Tolerance to the depressant effects of benzodiazepines is rapid, but tolerance to the anxiolytic effects develops slowly and to a limited extent. Although abusers use very high doses, most long-term users persist at daily doses in the low therapeutic range (10-20 mg of diazepam or its equivalent) without dose escalation. Physical dependence is a risk associated with long-term use, even at therapeutic doses. The withdrawal syndrome is mild at low doses. Continued self-administration of low therapeutic doses is maintained to alleviate withdrawal symptoms. The advances in the recent understanding of the molecular biology of the benzodiazepine receptor gives hope to the development of new anxiolytic compounds with less dependence liability than the present ones.