Obesity is a serious health problem in the U.S. Concerns about weight contribute to smoking initiation, interfere with smoking cessation efforts, and promote relapse. Anti-obesity medications have been successful in regulating weight in nonsmokers and ex- smokers; however, use of these agents is restricted due to undesirable side effects and unknown long-term consequences. This study will investigate the effects of a novel stimulant medication, modafinil, on food intake, verbal reports of drug effect, performance, and cardiovascular activity in normal, healthy men and women. These effects will be compared with those of phenylpropanolamine, an adrenergic anorectic agent with limited abuse liability, and d-amphetamine, an adrenergic anorectic with well-documented abuse liability. Participants will complete 10 sessions and will receive a single oral dose of the following drugs: modafinil (placebo, 1.75 mg/kg, 3.5 mg/kg, or 7.0 mg/kg), amphetamine (0.035mg/kg, 0.07 mg/kg, 0.14 mg/kg), and phenylpropanolamine (0.27 mg/kg, 0.535 mg/kg, 1.07 mg/kg) on separate occasions. Brief (15 minute) performance batteries will be administered at hourly intervals following drug administration for 6 hours. Forty-five minutes of free time will separate successive performance testing intervals allowing participants to watch television, read, listen to music, or eat. Behavioral and subjective effects including performance, food intake, activity, mood and other subjective effects such as hunger and thirst will be monitored during the study. Preclinical studies suggest that modafinil decreases appetite and reduces frequency of eating. However, unlike anorectic adrenergic agents, modafinil displays a low incidence of side effects. In addition, modafinil exhibits low abuse potential. These characteristics make modafinil uniquely suited for the treatment of obesity and may have important implications in the area of drug abuse. If proven to be an effective anorectic agent, modafinil may reduce adverse health consequences of drug use and enhance treatment efficacy in individuals who use tobacco smoking as a means of regulating their weight.
| Makris, Angela P; Rush, Craig R; Frederich, Robert C et al. (2007) Behavioral and subjective effects of d-amphetamine and modafinil in healthy adults. Exp Clin Psychopharmacol 15:123-33 |
| Makris, Angela P; Rush, Craig R; Frederich, Robert C et al. (2004) Wake-promoting agents with different mechanisms of action: comparison of effects of modafinil and amphetamine on food intake and cardiovascular activity. Appetite 42:185-95 |
