Drug abuse is usually taken to mean the use of an illicit drug or the excessive or nonmedical use of a licit drug. It also denotes the deliberate use of chemicals that generally are not considered drugs by the lay public but may be harmful to the user. A primary motivation for drug abuse appears to be the anticipated feeling of pleasure derived from the CNS effects of the drug. The older term “physical (physiologic) dependence” is now generally denoted as dependence, whereas “psychological dependence” is more simply called addiction.
THE DOPAMINE HYPOTHESIS OF ADDICTION
Dopamine in the ventral tegmental area and the nucleus accumbens of the mesolimbic system appears to play a primary role in the expression of “reward,” and excessive dopaminergic stimulation may lead to reinforcement such that the rewarded behavior may become compulsive—a common feature of addiction. Though not the only neurochemical characteristic of drugs of abuse, it appears that most addictive drugs have actions that include facilitation of the effects of dopamine in the CNS.
The sedative-hypnotic drugs are responsible for many cases of drug abuse. The group includes ethanol, barbiturates, and benzodiazepines. Benzodiazepines are commonly prescribed drugs for anxiety and, as Schedule IV drugs, are judged by the US government to have low abuse liability (Table 32–1). Short-acting barbiturates (eg, secobarbital) have high addiction potential. Ethanol is not listed in schedules of controlled substances with abuse liability although it is clearly a heavily abused drug.
TABLE 32–1Schedules of controlled drugs.a |Favorite Table|Download (.pdf) TABLE 32–1 Schedules of controlled drugs.a
|Schedule ||Criteria ||Examples |
|I ||No medical use; high addiction potential ||Flunitrazepam, heroin, LSD, mescaline, PCP, MDA, MDMA, STP |
|II ||Medical use; high addiction potential ||Amphetamines, cocaine, methylphenidate, short acting barbiturates, strong opioids |
|III ||Medical use; moderate abuse potential ||Anabolic steroids, barbiturates, dronabinol, ketamine, moderate opioid agonists |
|IV ||Medical use; low abuse potential ||Benzodiazepines, chloral hydrate, mild stimulants (eg, phentermine, sibutramine), most hypnotics (eg, zaleplon, zolpidem), weak opioids |
Sedative-hypnotics reduce inhibitions, suppress anxiety, and produce relaxation. All of these actions are thought to encourage repetitive use. Although the primary actions of sedative-hypnotics involve facilitation of the effects of GABA or antagonism at cholinergic nicotinic receptors, these drugs also enhance brain dopaminergic pathways, the latter action possibly related to the development of addiction. The drugs are CNS depressants, and their depressant effects are enhanced by concomitant use of opioid analgesics, antipsychotic agents, marijuana, and any other drug with sedative properties. Acute overdoses commonly result in death through depression of the medullary respiratory and cardiovascular centers (...