Effects of repeated oral methamphetamine administration in humans.
BACKGROUND
Although methamphetamine use has increased over the past several years, few studies have evaluated the effects of repeated methamphetamine administration in humans.


OBJECTIVE
Because methamphetamine is often taken in a pattern of repeated use followed by a period of abstinence, the present study sought to evaluate the effects of repeated methamphetamine administration in humans. The hypothesis was that tolerance would develop to methamphetamine's effects.


METHODS
Seven normal, healthy volunteers participated 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.


RESULTS
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 1st day of methamphetamine administration. In contrast, numerous "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 after methamphetamine administration, relative to baseline.


CONCLUSIONS
The pattern of methamphetamine's positive subjective effects were altered with chronic administration such that tolerance, or a decreased effect, occurred after repeated administration. In contrast, methamphetamine's negative subjective effects increased over days. These results suggest that in this population of normal volunteers, the abuse liability of oral methamphetamine is relatively low.
Comer
S D
SD
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. sdc10@columbia.edu
Hart
C L
CL
Ward
A S
AS
Haney
M
M
Foltin
R W
RW
Fischman
M W
MW
D000328:Adult; D000339:Affect / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004435:Eating / Q000187:drug effects; D004644:Emotions / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects; D011795:Surveys and Questionnaires
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D003913:Dextroamphetamine