Abstract
Methamphetamine abuse is a significant public health concern. Although widely studied in laboratory animals, little is known about the abuse-related behavioral effects of methamphetamine relative to other abused stimulants in controlled laboratory settings in humans. The aim of this study was to examine the discriminative stimulus, subject-rated, performance, and cardiovascular effects of methamphetamine in humans. In the present study, subjects first learned to discriminate 10 mg of oral methamphetamine from placebo. After acquiring the discrimination (≥80% drug-appropriate responding on four consecutive sessions), a range of oral doses of methamphetamine (2.5-15 mg), d-amphetamine (2.5-15 mg), methylphenidate (5-30 mg), and triazolam (0.0625-0.375 mg) was tested. Methamphetamine functioned as a discriminative stimulus and produced prototypical stimulant-like subject-rated effects. d-Amphetamine and methylphenidate produced dose-related increases in methamphetamine-appropriate responding, whereas triazolam did not. d-Amphetamine and methylphenidate produced stimulant-like behavioral effects, whereas triazolam produced sedative-like effects. Methamphetamine, but no other drug, increased heart rate, systolic pressure, and diastolic pressure significantly above placebo levels. Performance in the Digit-Symbol Substitution Test was not affected by any of the drugs tested. Overall, these results demonstrate that the acute behavioral effects of methamphetamine, d-amphetamine, and methylphenidate overlap extensively in humans, which is concordant with findings from preclinical studies. Future studies should assess whether the similarity in the behavioral effects of methamphetamine and related stimulants can be extended to other behavioral assays, such as measures of reinforcement, in humans.
Footnotes
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This work was supported by the National Institutes of Health National Institute of Drug Abuse [Grant DA017711].
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doi:10.1124/jpet.108.147124.
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ABBREVIATIONS: ADHD, attention deficit hyperactivity disorder; THC, tetrahydrocannabinol; ARCI, Addiction Research Center Inventory; MBG, morphine-benzedrine group; PCAG, pentobarbital, chlorpromazine, alcohol group; BG, Benzedrine group; A, amphetamine; DSST, Digit-Symbol Substitution Test; ANOVA, analysis of variance; METH, methamphetamine; d-AMP, d-amphetamine; MPH, methylphenidate; TRZ, triazolam.
- Received October 7, 2008.
- Accepted December 19, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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