Clinical pharmacokinetics of non-opiate abused drugs.

The present review discusses the available data on the kinetic properties of non-opiate abused drugs including psychomotor stimulants, hallucinogens and CNS-depressants. Some of the drugs of abuse reviewed here are illicit drugs (e.g. cannabis, cocaine), while others are effective pharmacological agents but have the potential to be abused (e.g. benzodiazepines). Although some of the drugs mentioned in this review have been in use for centuries (e.g. caffeine, nicotine, cocaine, cannabis), knowledge of their kinetics and metabolism is very recent and in some cases still incomplete. This is partially due to the difficulties inherent in studying drugs of abuse in humans, and to the complex metabolism of some of these drugs (e.g. cannabis, caffeine) which has made it difficult to develop sensitive assays to determine biological pathways. Although drugs of abuse may have entirely different intrinsic pharmacological effects, the kinetic properties of such drugs are factors contributing to abuse and dependence. The pharmacokinetic properties that presumably contribute to self-administration and drug abuse include rapid delivery of the drug into the central nervous system and high free drug clearance. Kinetic characteristics also play an important role in the development of physical dependence and on the appearance of a withdrawal syndrome: the longer the half-life, the greater the likelihood of the development of physical dependence; the shorter the half-life, the earlier and more severe the withdrawal. The balance between these 2 factors, which has not yet been carefully studied, will also influence abuse patterns. The clinical significance of kinetic characteristics with respect to abuse is discussed where possible.