Acute responses to drugs are known to vary across individuals and across settings, in ways that may be related to their potential for abuse. The proposed studies will investigate several organismic and environmental variables which influence subjective and behavioral responses to acute drug administration in humans. The subjective, physiological and behavioral effects of low, acute doses of drugs will be assessed in normal volunteers under double-blind, placebo-controlled conditions. The first series of studies examines organismic, or subject-related variables and the second series of studies examines environmental variables. The first series of studies will extend our previous findings of individual differences in responses to ethanol and benzodiazepines: One study will examine individual differences in sensitivity to ethanol and triazolam, and a second study will examine the stability of responses to the drugs over a two-month period. Another study will examine the effects of prior exposure to therapeutically-administered benzodiazepines on subsequent acute response these drugs. Another study will examine responses to stimulant and sedative/hypnotic drugs in women at three phases of the menstrual cycle: Despite the practical and theoretical implications of this issue, little is known about variations in drug effects related to levels of circulating ovarian hormones or other cycle-related events. The studies examining environmental determinants of drug responses will focus on the influence of psychosocial context on responses to amphetamine and to ethanol. Specifically, these studies will investigate how the presence or absence of other individuals during the period of acute drug effects alters subjective response to the drugs. The studies proposed in this application will extend previous findings from this laboratory, investigating variables that affect the abuse potential of drugs. In addition, the results may have implications for our understanding of the basic mechanisms underlying the effects of psychoactive drugs.