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, for example, solvents, 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. A classification system for these drugs is set forth in Figure 32–1.
Neuropharmacologic classification of addictive drugs by primary target. DA, dopamine; GABA, γ-aminobutyric acid; GHB, γ-hydroxybutyric acid; GPCRs, G-protein-coupled receptors; THC, Δ9-tetrahydrocannabinol. (Reproduced with permission from Katzung BG, Vanderah TW: Basic & Clinical Pharmacology, 15th ed. New York, NY: McGraw Hill; 2021.)
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), however short-acting benzodiazepines (eg, alprazolam) have high addiction potential when used long-term. 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. ||Download (.pdf) TABLE 32–1 Schedules of controlled drugs.
|Schedule ||Criteria ||Examples |
|I ||No medical use; high addiction potential ||Flunitrazepam, heroin, LSD, mescaline, PCP, MDA, MDMA, STP, GHB |
|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 ...