Dose tolerance to lorazepam develop with once weekly dosing?

The effect of once weekly administration of lorazepam (2.5 mg) to benzodiazepine-naive student volunteers was assessed in a number of performance tests and on self-ratings. Tolerance developed to the effects of lorazepam on finger-tapping and on self-ratings of dizziness. No tolerance was observed to the drug-induced impairment in a nonsense-syllable paired associate learning test or to the effects on self-ratings of sedation or on heart rate. It is suggested that the reduced impairment in the digit-symbol substitution test observed in weeks 2 and 3 of lorazepam treatment was due to a 'masked' practice effect rather than to tolerance. Test-retest correlation coefficients were calculated for all the tests used. The effect of lorazepam in each test was also correlated with its effect in the other tests. There were significant correlations in performance on placebo in the finger-tapping (r = 0.66), digit-symbol substitution (r = 0.94), symbol copying (r = 0.96) and nonsense-syllable learning (r = 0.74) tests. It is suggested that benzodiazepine experience should be given to drug-naive subjects before they are used in cross-over experiments that involve this class of compound, since the major change in impairment occurred between the first and second exposure to lorazepam.