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Related Experiment Videos

Dose tolerance to lorazepam develop with once weekly dosing?

S E File, R G Lister

    British Journal of Clinical Pharmacology
    |December 1, 1983
    PubMed
    Summary
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    Weekly lorazepam (2.5 mg) showed tolerance in some tests but not others for naive students. Practice effects may mask true lorazepam tolerance in certain cognitive tasks.

    Area of Science:

    • Pharmacology
    • Neuroscience
    • Cognitive Psychology

    Background:

    • Benzodiazepines are commonly prescribed medications with potential for tolerance.
    • Understanding tolerance development is crucial for effective and safe therapeutic use.
    • Lorazepam is a widely used benzodiazepine with anxiolytic and sedative properties.

    Purpose of the Study:

    • To investigate the development of tolerance to the effects of once-weekly lorazepam administration in benzodiazepine-naive individuals.
    • To assess lorazepam's impact on various performance tests and self-reported measures.
    • To explore potential practice effects masking true tolerance in cognitive tasks.

    Main Methods:

    • Once-weekly administration of lorazepam (2.5 mg) to benzodiazepine-naive student volunteers.

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  • Assessment using performance tests (e.g., finger-tapping, digit-symbol substitution, paired associate learning) and self-ratings (dizziness, sedation).
  • Calculation of test-retest correlation coefficients and correlation of lorazepam effects across tests.

    • Main Results:

    • Tolerance developed to lorazepam's effects on finger-tapping and self-rated dizziness.
    • No tolerance observed for impairment in paired associate learning, self-rated sedation, or heart rate.
    • Reduced impairment in digit-symbol substitution was attributed to practice effects, not tolerance.
    • Significant correlations in performance were noted on placebo across multiple tests.

    Conclusions:

    • Tolerance to lorazepam is task-dependent, with some cognitive functions showing no habituation.
    • Practice effects can influence performance, potentially masking true drug tolerance in naive populations.
    • Benzodiazepine-naive subjects should ideally have prior exposure before participating in cross-over studies involving this drug class.