Effects of repeated oral methamphetamine administration in humans

Rationale: Although methamphetamine use has increased over the past several years, few studies have evaluated the effects of repeated methamphetamine administration in humans. Objectives: Because methamphetamine is often take n in a pattern of repeated use followed by a period of abstinence, the pres ent study sought to evaluate the effects of repeated methamphetamine admini stration in humans. The hypothesis was that tolerance would develop to meth amphetamine's effects. Methods: Seven normal, healthy volunteers participat ed in a 15-day residential study. Participants completed subjective-effects questionnaires and psychomotor performance tasks repeatedly throughout the experimental day. Oral methamphetamine (5, 10 mg BID) was administered on days 4-6 and 10-12; placebo was administered on all other study days. Resul ts: Relative to placebo baseline, only two "positive" subjective ratings (" I feel a good drug effect" and "I feel high") were significantly elevated, and only on the Ist day of methamphetamine administration. In contrast, num erous "negative" ratings, including "I feel..." "a bad drug effect," "dizzy ," and "flu-like symptoms" were elevated on the 3rd day of methamphetamine administration. Total caloric intake decreased and sleep was disrupted afte r methamphetamine administration, relative to baseline. Conclusions: The pa ttern of methamphetamine's positive subjective effects were altered with ch ronic administration such that tolerance, or a decreased effect, occurred a fter repeated administration. In contrast, methamphetamine's negative subje ctive effects increased over days. These results suggest that in this popul ation of normal volunteers, the abuse liability of oral methamphetamine is relatively low.