Effects of flunitrazepam on cognitive functions

Abstract

The effects of various oral doses (1, 2, 4 mg) of flunitrazepam on vigilance, attention, immediate memory, short-term memory, learning, non-consolidated and consolidated long-term memory were determined. Twelve healthy young male volunteers were given placebo or flunitrazepam in a double-blind, random latin-square sequence, crossing over every 2 weeks. Volunteers completed a battery of tests at night, 3.5 h after drug administration, and in the morning, 10 h after drug administration. Flunitrazepam 1 mg did not significantly impair any of the functions tested at night, while 4 mg impaired vigilance, attention, immediate memory, short-term verbal memory and learning. The impairments of immediate and short-term memory seem to be related and proportional to reductions in vigilance and attention. Doses of 2 mg and 4 mg impaired the speed of learning but did not decrease the amount of material learned. Flunitrazepam caused dose-related impairment of long-term memory, both consolidated and not. This reduction of long-term memory does not seem to be related to the impairments of vigilance, attention or learning. The lowest dose did not modify vigilance and learning in any subject, improved attention in half of the subjects but reduced long-term memory in a similar number of subjects. Therefore, our results indicate selective impairment of long-term memory. Since there were no differences between the effects on consolidated and non-consolidated memory, the amnesic effect of flunitrazepam seems to be due to a decrease in the storage of memory traces. There were no clear generalized residual effects in the morning after administration.

Impairment of memory and plasma flunitrazepam levels

“…Recent studies have conÞrmed previous results (Smirne et al 1989) i.e. that ßunitrazepam impairs memory in direct tasks which employ explicit retrieval processes, but not indirect tasks involving implicit retrieval (Pompéia et al 1996a, b).…”

“…After centrifugation, plasma was stored at 25 ºC until assay. Flunitrazepam was extracted and measured by GLC-ECD as previously described (Bareggi et al 1988 In the present study, the tests were chosen according to their degree of sensitivity to the e¤ects of benzodiazepines as established in previous studies (Smirne et al 1989; Bareggi et al 1991).…”

“…Others were constructed in-house and have been previously described (Smirne et al 1989;Bareggi et al 1991). In each session, parallel versions of similar di¦culty were used for each test.…”

“…Since the di¤erent e¤ects of BZs, and of ßuni-trazepam in particular, are clearly dose-dependent (Smirne et al 1989), the relationship between concentrations of the drug and its e¤ects may help in understanding its mechanism and in di¤erentiating between the various e¤ects at high and low concentrations.…”

High dose benzodiazepines prolong reaction times in chronic users who have major depressive and/or anxiety disorders

“…In most of these studies, BZD administration prolonged RTs for a duration up to 6 weeks [6][7][8][9][10][11]. Only two small studies did not find prolonged RTs after BZD intake [12,13].…”