Lorazepam and meprobamate dose effects in humans: behavioral effects and abuse liability

JD Roache and RR Griffiths

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

On a residential research ward, the acute effects of placebo, lorazepam (LZ) (1.5-9.0 mg) and meprobamate (MEP) (600-3600 mg) were examined using a within-subject double-blind Latin Square design in nine male subjects with histories of drug abuse. Drug effects were assessed with objective performance tasks, subject estimates of performance, staff ratings of drug effects and subject ratings of drug effects, sleep, mood, drug liking and monetary street value. Generally, both LZ and MEP produced comparable dose-related effects; LZ had a more rapid onset of action and on several measures showed a more shallow dose-response curve than MEP. With LZ, but not MEP, subjects under-estimated the degree to which their performance was impaired and under-rated drug effects as compared to analogous staff ratings. Both drugs produced sedation-like subject ratings of mood and sleep but generally did not produce tranquilization-like ratings. MEP produced subject ratings of drug liking and monetary street value which were equal to or in some cases greater than those of LZ. Relative potency estimations showed that LZ was 510 to 783 times more potent than MEP in producing performance impairment but was only 370 times more potent than MEP in producing subject ratings of drug liking. Overall, these data indicate that the likelihood of abuse of MEP is at least equal to if not greater than that of LZ although LZ may have a greater likelihood of producing adverse behavioral effects such as a performance impairment and under- estimates of the degree of impairment. These data in conjunction with previous results from this laboratory show that the behavioral effects of benzodiazepines can be differentiated from those of other types of sedative/anxiolytics and that MEP displays characteristics of a barbiturate-like profile of action.

Volume 243, Issue 3, pp. 978-988, 12/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics

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