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Published on: November 21, 2012
Effects of repeated oral methamphetamine administration in humans
S D Comer1, C L Hart, A S Ward
1Division 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
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 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.
Insights
Repeated oral methamphetamine use led to tolerance in positive subjective effects but increased negative side effects like dizziness and flu-like symptoms in healthy volunteers. Abuse liability appears low in this group.
Area of Science:
- Pharmacology
- Neuroscience
- Clinical Psychology
Background:
- Methamphetamine use has risen, yet human studies on repeated administration effects are scarce.
- Understanding tolerance and adverse effects is crucial for public health.
- The study addresses a gap in knowledge regarding chronic methamphetamine administration in humans.
Purpose of the Study:
- To evaluate the effects of repeated oral methamphetamine administration in healthy human volunteers.
- To test the hypothesis that tolerance develops to methamphetamine's subjective and performance-impairing effects.
- To assess changes in subjective ratings and psychomotor performance over a 15-day study period.
Main Methods:
- Seven healthy volunteers participated in a 15-day residential study.
- Oral methamphetamine (5, 10 mg BID) or placebo was administered on specific days.
- Subjective-effects questionnaires and psychomotor performance tasks were administered repeatedly.
Main Results:
- Positive subjective effects (e.g., "high") decreased with repeated methamphetamine administration, indicating tolerance.
- Negative subjective effects (e.g., "bad drug effect," "dizzy") increased by the third day of administration.
- Caloric intake decreased and sleep was disrupted during methamphetamine administration periods.
Conclusions:
- Tolerance developed to the positive subjective effects of oral methamphetamine.
- Negative subjective effects and physiological disruptions worsened with repeated administration.
- The abuse liability of oral methamphetamine was found to be relatively low in this cohort of normal volunteers.
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