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A triazolam/amphetamine dose–effect interaction study: dissociation of effects on memory versus arousal

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Abstract

Rationale

In addition to producing robust memory impairment, benzodiazepines also induce marked sedation. Thus, it is possible that the observed amnestic effects are secondary to more global sedative effects and do not reflect a specific primary benzodiazepine effect on memory mechanisms.

Objective

The objective was to use the nonspecific stimulant d-amphetamine to dissociate the sedative and memory-impairing effects of the benzodiazepine triazolam.

Materials and methods

Single oral doses of placebo, triazolam alone (0.25, 0.50 mg/70 kg), d-amphetamine sulfate alone (20, 30 mg/70 kg), and triazolam (0.25, 0.50 mg/70 kg) and d-amphetamine sulfate (20, 30 mg/70 kg) conjointly (at all dose combinations) were administered to 18 healthy adult participants across nine sessions in a double-blind, staggered-dosing, crossover design. In addition to standard data analyses, analyses were also conducted on z-score standardized data, enabling effects to be directly compared across measures.

Results

Relative to the sedative measures, the memory measures generally exhibited a pattern of less reversal of triazolam’s effects by d-amphetamine. The memory measures ranged in degree of reversal such that the most reversal was observed for reaction time on the n-back working memory task, and the least reversal was observed for accuracy on the Sternberg working memory task, with most measures showing an overall pattern of partial reversal.

Conclusions

Benzodiazepines have specific effects on memory that are not merely a by-product of the drugs’ sedative effects, and the degree to which sedative effects contribute to the amnestic effects varies as a function of the particular memory process being assessed.

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Acknowledgment

This project was supported by the National Institute on Drug Abuse Research Grant DA-11936. The authors thank Crystal Barnhouser, Kristina Burns, and Koty Nadeau for protocol management, John Yingling for computer programming assistance and technical support, and Linda Felch and Paul Nuzzo for assistance with data analysis.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Behavioral Biology Research Center, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Baltimore, MD, 21224, USA

    Miriam Z. Mintzer & Roland R. Griffiths

  2. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA

    Roland R. Griffiths

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  1. Miriam Z. Mintzer
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  2. Roland R. Griffiths
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Correspondence to Miriam Z. Mintzer.

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Mintzer, M.Z., Griffiths, R.R. A triazolam/amphetamine dose–effect interaction study: dissociation of effects on memory versus arousal. Psychopharmacology 192, 425–440 (2007). https://doi.org/10.1007/s00213-007-0726-y

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  • DOI: https://doi.org/10.1007/s00213-007-0726-y

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