be key factors in the formulation of theories regarding the etiology of drug abuse. Physiological influences that may exacerbate an individual's vulnerability to drug abuse could include neurochemical system impairment and heightened susceptibility to a drug because of biologically determined responsiveness. Although there has been substantial research on individual differences in response to ethanol and nicotine, less is known regarding the effects of the major classes of illicit drugs of abuse, such as opioids, stimulants, and cannabis.
Metabolic Variations There are large interindividual and interethnic variations in the outcome of alcohol use and abuse (Goedde et al., 1992). Studies have demonstrated that, in contrast to Caucasians, many Asians are biologically protected from becoming alcoholics because of the polymorphism of two liver enzymes: aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase-2 (ADH2). The Asians appear to have a protective factor in the form of inactive ALDH2 and high frequencies of atypical ADH2 (Higuchi et al., 1995), whereas Caucasians primarily have only active ALDH2 and usual ADH2 (Yoshida et al., 1991). The inactive form of ALDH2 is considered protective against alcoholism because it allows high levels of acetaldehyde to accumulate in the blood and causes adverse reactions, known as the flushing response (Thomasson et al., 1991; Yoshida et al., 1991). This increase in acetaldehyde blood levels after ingestion of ethanol appears to have a protective influence on further ingestion and thus appears to lower the rate of alcoholism (Bosron and Li, 1986).
Efficient ethanol metabolism may enhance the risk of alcoholism by allowing ingestion of a sufficient quantity to mediate the addictive potential of alcohol. Studies of the male offspring of alcoholics have demonstrated that the ability to tolerate large quantities of alcohol with fewer subjective effects may be a potent signal of the subsequent development of alcoholism (Schuckit, 1984, 1985). Thus, the inability to metabolize a drug may be a protective influence in continued exposure, whereas efficient metabolism may permit high levels of exposure conducive to the development of abuse and dependence.
Biochemical Markers Monoamine oxidase (MAO) is a widely studied biochemical marker for alcohol abuse. Several studies comparing alcoholics with nonalcoholics have found decreased platelet MAO activity levels among alcohol abusers (von Knorring et al., 1985; Pandey et al., 1988; Tabakoff et al., 1988). MAO is an enzyme that is important in the metabolism of a variety of brain neurotransmitters that affect behavior, including dopamine, norepinephrine, and serotonin. Although other biochemical markers have been investigated, no consistent findings have emerged.