A comparison of the psychometric effects of remoxipride with those of haloperidol,thioridazine, and lorazepam in healthy volunteers

In this placebo and verum (lorazepam 2 mg) controlled double-blind crossover study the acute effects of Remoxipride 50 mg and 100 mg; Haloperidol 2·5 mg; and Thioridazine 50 mg were examined in 18 healthy volunteers. CNS function was assessed using a battery of psychometric measures, viz: Critical Flicker Fusion Threshold (CFFT); Choice Reaction Time (CRT); Tracking Accuracy (RMS) and Peripheral Reaction Time (PRT); Sternberg Memory Scanning (SMS); Word Memory (WM) as well as Line Analogue Ratings of subjective sedation (LARS) and the Leeds Sleep Evaluation Questionnaire (LSEQ). Both doses of remoxipride were associated with a reduction of CFFT: 0·9 Hz for 50 mg and 1·3 Hz for 100 mg. The 100 mg dose caused an increase (impairment) in CRT total time of 38 msec. Haloperidol reduced CFFT, while thioridazine and lorazepam impaired performance on the majority of objective measures, as expected for known sedative drugs. Thioridazine led to hypotension in three subjects, and to subjective sedation (LARS), but no treatment affected responses on the LSEQ administered the morning of the day following treatment. These results show that remoxipride has some depressant effects on CNS function, but that these are less prominent than those of sedative neuroleptics such as thioridazine.     

A comparative pharmacokinetic and dynamic evaluation of alprazolam sustained-release, bromazepam, and lorazepam

Sustained-release (SR) alprazolam may facilitate compliance with oral benzodiazepine treatment of panic disorders that currently requires doses administered three or four times daily. To compare the pharmacokinetic, psychomotor performance, and subjective effects of alprazolam SR (1.5 mg), bromazepam (3 mg taken three times daily), and lorazepam (1 mg taken three times daily), 13 male volunteers (aged 20-45 years) randomly received on four separate occasions one of these medications or placebo. Once before and 11 times after drug administration, the subjects were tested using psychomotor performance tests (manual tracking and digit-symbol substitution test [DSST]) and computerized questionnaires (such as the Tufts University Benzodiazepine Scale [TUBS], the Addiction Research Center Inventory, and the visual analog scales) to determine the subjective effects of the drugs. Blood samples for the determination of the plasma levels of the drugs were collected before and 17 times after the drug was administered. A peak plateau of plasma alprazolam began approximately 6 hours after the dose, which was later than the initial peaks for lorazepam and bromazepam (1-2 hours after the dose). Once this plateau had begun, alprazolam SR sustained that concentration better than did the other two formulations. Of the 10 measures on which the response averaged for the first 14 hours differed among drugs (p < 0.05), bromazepam differed from placebo on two measures, lorazepam on four (including DSST Performance and TUBS Sedation), and alprazolam SR on nine (including all four affected by lorazepam). Lorazepam and alprazolam, but not bromazepam, produced significantly more sedation than placebo. The doses of the three drugs were not equipotent in sedation and mood effects. None of the drugs tested differed from placebo on measures relevant to abuse liability.     

Sedation and memory: studies with a histamine H-1 receptor antagonist

The influence of sedation on the effect of an H-1 receptor antagonist on various cognitive functions, including memory, were evaluated.Diphenhydramine (50, 75 and 100 mg) and lorazepam (0.5 and 1.5 mg) were given on single occasions to 12 healthy volunteers (six males, six females) aged 20-33 (mean 23.4) years. Subjective assessments of sedation, sleep latencies, digit symbol substitution, choice reaction time, sustained attention and memory recall were studied 1.0 h before and 0.5, 2.0 and 3.5 h after drug ingestion. The study was double blind, placebo controlled and with a crossover design.With all doses of diphenhydramine there was subjective sedation, reduced sleep latencies and impairments in performance on the digit symbol substitution, choice reaction time and sustained attention tasks. No effects were observed with 0.5 mg lorazepam. With 1.5 mg lorazepam there was subjective sedation, fewer digit symbol substitutions, slowed choice reaction time, impaired attention and memory, but no effect on sleep latencies. Contrast analysis of data measured at all time points showed that although there was no difference in the effect of diphenhydramine (100 mg) and lorazepam (1.5 mg) on those tasks without a memory component, response times were slower with lorazepam on those tasks with a memory component. However, both 100 mg diphenhydramine and 1.5 mg lorazepam impaired prompted recall measured at 2 h post-ingestion only. It is considered that impaired memory is not necessarily associated with sedation, and that impairment of memory with drugs that lead to sedation may be effected through neuronal systems independent of those that affect arousal.     

Effects of alprazolam and lorazepam on catecholaminergic and cardiovascular activity during supine rest,mental load and orthostatic challenge

Effects of oral alprazolam (0.5 and 1 mg) and lorazepam (2 mg) on sympathetic adrenomedullary activity and sedation were studied during supine rest, mental load (Color Word Test, CWT) and active standing (OCT), in 12 male volunteers in a randomized double-blind placebo-controlled cross-over design. Compared to placebo, alprazolam significantly increased subjective sedation, reduced plasma adrenaline and noradrenaline concentrations and mean blood pressure (MBP) during supine rest, and attenuated plasma adrenaline responses during the CWT and the OCT; these effects during the CWT and OCT appeared to be dose-dependent. In comparison with lorazepam (2 mg), alprazolam (1 mg) showed reduced MBP levels during supine rest, whereas lorazepam showed a higher heart rate level during supine rest, a reduced plasma noradrenaline response to the OCT and a performance deterioration to the CWT. There were no differences between alprazolam (1 mg) and lorazepam regarding subjective sedation. Although the benzodiazepines were similar regarding their increase of sedation, alprazolam and loraze- pam induced differential effects on sympathetic adrenomedullary activity during rest and stress, whereby suppression of adrenomedullary activity may be specific for alprazolam. Received: 13 March 1996 / Final version: 6 June 1996     

Sleep laboratory studies on single dose effects of suriclone.

1. In a double-blind, placebo-controlled sleep laboratory study single doses of suriclone, a new non-benzodiazepine anxiolytic binding to benzodiazepine receptors, were investigated with respect to sleep and awakening. 2. Sixteen healthy young volunteers spent 10 nights in the sleep laboratory: 1 adaptation night, 1 baseline night and 4 drug nights (placebo; 0.2 mg, 0.4 mg suriclone; 2 mg lorazepam as reference drug) and 4 subsequent wash-out nights (drug-interval: 1 week). Somnopolygraphic investigations (22.30 h to 06.00 h) were commenced 0.5 h after drug-intake. A self-rating scale for sleep and awakening quality as well as psychometric tests were completed in the morning. 3. Hypnotic effects were most pronounced after lorazepam in regard to total sleep time and sleep efficiency. After lorazepam as well as after 0.4 mg suriclone nocturnal awakenings decreased significantly as compared with placebo, which was reflected in an improved subjective sleep quality after both dosages. Suriclone 0.2 mg did not induce any alterations in all night sleep. 4. In the morning, well-being, drowsiness and reaction time performance deteriorated after lorazepam as compared with placebo but not after suriclone. The latter was significantly superior to lorazepam with respect to subjective awakening quality, well-being, emotional rapport, drowsiness and attention. 5. Blood pressure and pulse remained unchanged after all of the drugs. Critical flicker frequency and muscle strength decreased only after lorazepam as compared with placebo.     

Long-term comparison of alprazolam, lorazepam and placebo in patients with an anxiety disorder

In a double-blind, placebo-controlled study of 200 patients with moderate to moderately severe anxiety we compared the anxiolytic efficacy and safety of alprazolam and lorazepam. Dosing was flexible and ranged from 1 to 4.5 mg/day of alprazolam and from 2 to 9 mg/day of lorazepam. The mean daily dose at the end of the 16 week study was alprazolam 3.3 mg and lorazepam 5.1 mg. Both active drugs were significantly more effective than placebo in relieving the symptoms of anxiety on the Hamilton Anxiety Rating Scale, with a trend toward more improvement in the alprazolam group in the later weeks of the study. Target Symptoms, Physician's and Patient's Global Impressions and the Self Rating Symptom Scale indicate that alprazolam and lorazepam were superior to placebo. The major side effects were sedation and drowsiness; the frequency was similar for alprazolam and lorazepam and twice as high for active drug as placebo. An overall rating of side effect severity was not significantly different among the three groups.     

Pharmacodynamic effects of buspirone and clobazam.

1. The pharmacodynamic effects of buspirone and clobazam were compared in two volunteer studies. Acute doses of buspirone 5 mg, 10 mg and clobazam 10 mg were contrasted with placebo and a verum (lorazepam 1 mg), in a repeated measures design with 10 subjects assessed on a battery of psychometric tests at 1.5, 3.5, and 5.5 h post dose. For the combined results clobazam and the lower dose of buspirone (5 mg) were significantly contrasted with lorazepam on measures of subjective sedation, memory and choice reaction time (CRT). The higher dose of buspirone was not statistically different from lorazepam for all measures except memory; whilst contrasting significantly with placebo and clobazam on movement and total reaction time components respectively. Though failing to achieve significance, a similar trend was seen for critical flicker fusion (CFF) with buspirone 10 mg and lorazepam producing the lowest scores indicative of increased sedation. 2. Repeated doses of buspirone 5 mg twice daily, clobazam 10 mg twice daily, or placebo twice daily for 8 consecutive days were compared on the same battery of psychometric tests in a repeated measures design. Nine subjects were assessed on days 1, 3, and 8 of the study. Overall, memory performance significantly decreased with buspirone 5 mg in contrast to both clobazam and placebo whilst the opposite trend was seen with CFF. Clobazam significantly improved TRT in contrast to both placebo and buspirone. 3. These results indicate improved reaction time and memory performance with repeated dosing of clobazam in contrast to buspirone. Impairment following acute administration of buspirone appears limited to the higher (10 mg) dose.     

The effects of lormetazepam on aspects of memory,sleep and human performance

The effects of lormetazepam 1 mg, 1·5 mg, 2 mg, a verum—triazolam 0·5 mg and placebo were examined in ten normal female volunteers, on tests of psychomotor function, performance and analogue rating scales for subjective sedation, sleep and early morning behaviour. Results showed all doses of lormetazepam to be effective hypnotics and free from residual effects 10 h after drug ingestion when tested on critical flicker fusion threshold (CFF), choice reaction time (CRT), simultated car tracking task and Maddox wing. Acquisition and immediate recall of word lists was poorer following administration of lormetazepam 1·5 mg and triazolam 0·5 mg. On memory scanning, lormetazepam 1 mg was the only dose completely free from residual impairment 10 h following administration.     

Pharmacodynamics of milnacipran in young and elderly volunteers

AIMS: To investigate the pharmacodynamics of milnacipran in healthy young and elderly volunteers. METHODS: Randomized double-blind crossover designs were employed and a standardized psychometric battery was administered pre and post dose for both studies. In the first study 10 healthy young volunteers received milnacipran 12.5 mg, 25 mg, 50 mg, 100 mg as a single dose or matched placebo. The test battery was administered at baseline and at 1, 2, 4 and 6 h post dose. The second study compared the effects of milnacipran 75 mg (50 mg+25 mg) per day, amitriptyline 50 mg (25 mg+25 mg) per day and placebo for 3 days' dosing in healthy volunteers aged over 65 years. The test battery was administered at baseline and at 2, 10 and 24 h post dose. The psychometric battery included critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking (CTT) and tests of short-term memory (STM), subjective sedation (LARS) and subjective sleep (LSEQ). RESULTS: Milnacipran produced no significant dose related effects in the young volunteers. For the elderly, milnacipran significantly (P<0.05) raised CFF scores compared with placebo but had no significant effects on any of the other measures used. Amitriptyline, in contrast, significantly (P<0. 05) lowered CFF threshold, lengthened CRT and increased error on the CTT. On the subjective variables, LARS and LSEQ, amitriptyline increased ratings both of sedation and of difficulty in waking from sleep. CONCLUSIONS: The results showed that milnacipran at single doses of up to 100 mg in healthy young volunteers is free from disruptive effects on cognitive function and psychomotor performance. In addition, milnacipran 75 mg (50+25 mg) appears to be free of negative effects on cognitive function in elderly volunteers, where it seemingly improves performance on CFF. In contrast, the tricyclic antidepressant amitriptyline, used here as a positive internal control, significantly impaired performance in the elderly on the majority of psychometric measures used in this study. This finding not only validated the sensitivity of this current test battery but also indicates the potential behavioural toxicity of amitriptyline in clinical use in the elderly.     

The cognitive effect of alprazolam in healthy volunteers

Randomised, double blind placebo controlled crossover study has been performed to evaluate the effect of single dose of anxiolytic alprazolam on the cognitive function in 18 healthy male volunteers. The subject received a single dose of 0.75 mg, 1.75 mg alprazolam or placebo in randomised order. Performances on cognitive tests (immediate and delayed word recall test, digit symbol substitution test, critical fusion frequency and multiple choice reaction test) and subjective rating of the drug effect have been evaluated before and at several occasions after the administration of alprazolam or placebo. According to the results of the statistical analysis alprazolam impaired the performance in cognitive tests dose dependently and induced subjective sedation. The applied test battery proved to be capable to measure the effect of the drugs on the cognitive function in pharmacodynamic studies.     

A dose response study of the hypnotic effectiveness of alprazolam and diazepam in normal subjects

One group of eight normal young males was administered three doses of alprazolam (0.25, 0.5 and 1.0 mg) and placebo, while a second group of eight normal young males was given three doses of diazepam (2, 5, and 10 mg) and placebo in the same design. All subjects slept in the sleep laboratory for 10 nights, 2 consecutive nights each week for 5 consecutive weeks. The first 2 nights served as adaptation. During the next 4 weeks subjects received a random dose of alprazolam (or placebo) or a random dose of diazepam (or placebo) each week. Similar dose-related benzodiazepine effects were found on sleep with both medications. Alprazolam reduced percent stage 4 and REM sleep and increased stage 2 sleep and latency to REM. Diazepam decreased percent stage 1 and increased percent stage 2 sleep. No drug by dose interactions were found. It was concluded that, while both drugs had similar effects on sleep, alprazolam showed significant effects on REM sleep parameters and might be evaluated for possible antidepressant effect.Supported by the Upjohn Company     

Dose-dependent effects of intravenous lorazepam on cardiovascular activity,plasma catecholamines and psychological function during rest and mental stress

Dose-dependent effects of intravenously administered lorazepam on psychophysiological activity during rest and mental stress were studied in order to examine differential responses to doses which may induce anxiolysis or sedation. In a double-blind randomized cross-over study, nine male volunteers participated in a placebo and a lorazepam session, during which the subjects repeatedly performed a 10-min version of the Stroop Color Word Test (CWT), with 10 min of rest between the CWTs. Lorazepam was administered before each rest period in increasing doses of 0.0, 0.06, 0.13, 0.25 and 0.5 mg (total cumulative dose: 0.94 mg). Heart rate showed a dose-dependent decrease during rest with an ED₅₀ of 0.13 mg lorazepam, while lorazepam had no effect on the cardiovascular and plasma catecholamine response magnitudes to the CWT. Subjective fatigue and reaction time increased significantly after 0.94 mg lorazepam, while at the same dose vigor decreased; state anxiety after the CWT was not influenced by lorazepam. These data show differential effects of lorazepam on cardiovascular, biochemical and psychological function. While heart rate was suppressed at low doses during rest and reaction time and subjective fatigue increased at doses which induced sedation, state anxiety and physiological response patterns to the CWT were not influenced by lorazepam.     

Comparative drug effects and abuse liability of lorazepam, buspirone, and secobarbital in nondependent subjects.

The pharmacologic effects of lorazepam (2 mg), buspirone (20 mg, 10 mg), secobarbital (100 mg), and placebo were compared in 15 male, experienced, intermittent nontherapeutic drug users. All drugs produced a "drug effect," however, buspirone 20 mg was significantly less liked than were lorazepam, secobarbital, or buspirone 10 mg (p less than .05) but not placebo. Lorazepam was liked better than were other drugs only at 1 hour and only compared with buspirone 20 and placebo. Compared with other drugs, lorazepam drug effects were greater and resulted in more prolonged impairment of a motor tracking task, standing steadiness, and memory. Buspirone 20 mg significantly impaired memory at 1 hour compared with placebo. Subjects were more likely to identify buspirone as unfamiliar. Because buspirone 20 mg was less liked than were other drugs, dose escalation as part of drug abuse is not likely to occur. Lorazepam also was not particularly liked and was not different from placebo on most subjective abuse-relevant measures.     

A comparison of the sedative and amnestic effects of chlorpromazine and lorazepam

The effects of single doses of chlorpromazine (100mg) and lorazepam (0.5, 1 and 2mg) were compared with placebo in a battery of tests of information processing, working and semantic memory. Peak saccadic velocity was used to provide a precise and reliable measure of sedation and its results were found to be consistent with those using visual analogue rating scales. Chlorpromazine 100 mg was equally sedative to lorazepam 2 mg. Lorazepam caused dose-dependent deterioration in performance in many of the memory tests, whereas an equally sedative dose of chlorpromazine did not. These data therefore support the view that benzodiazepine-induced amnesia is not secondary to sedation. Peak saccadic velocity has considerable advantages over visual analogue scales as a measure of sedation, since it is objective and has a demonstrated low coefficient of variation. It is suggested that saccadic eye movement measurement will permit considerably more reliable and precise separation of the sedative and amnestic effects of drugs and will allow investigation of amnesia caused by clinically relevant doses of psychotropic drugs. Received: 22 November 1995/Final version: 7 June 1996     

Differential effects of alprazolam on the baseline and fear-potentiated startle reflex in humans: a dose-response study

RATIONALE: The "fear-potentiated startle" paradigm has been extensively used in animal studies, and more recently in human experimental psychopharmacology to evaluate the effects of anxiogenic and anxiety-relieving drugs. Previous human studies have shown that both the baseline and the fear-potentiated responses can be inhibited by anxiety-relieving drugs, suggesting drug activity on two different emotional states, the former reflecting a resting condition and the latter more akin to pathological anxiety. OBJECTIVES: To examine to which extent the reductions induced by a benzodiazepine on the basic and the fear-potentiated startle responses are of equal intensity, and whether or not the drug shows a predominant, i.e., selective, effect on either. METHODS: The effects of three increasing doses of the benzodiazepine alprazolam (0.25, 0.5, and 1.0 mg) were assessed on the human baseline and fear-potentiated startle responses. Twelve healthy volunteers attended the laboratory on four experimental days and received either alprazolam or placebo according to a double-blind crossover balanced design. Startle recordings were undertaken 2 h after drug intake. Fear potentiation was implemented by means of an electric-shock-anticipation experimental procedure. Additionally, subjective self-reports of sedation and anxiety and psychomotor performance were obtained at 2 and 3 h, respectively, after drug administration. RESULTS: Alprazolam dose-dependently impaired psychomotor performance and produced increases in subjective anxiolytic activity and sedation, although the latter did not reach statistical significance. Additionally, the drug reduced the magnitude of the startle response both in the absence and in the presence of a threat-related cue, although a differentially greater inhibitory effect was seen on the fear-potentiated response as the dose increased. CONCLUSIONS: Alprazolam showed a greater inhibitory effect on the fear-potentiated startle than on the baseline reflex, suggesting a more selective action of the drug on those structures mediating potentiation of the behavioral response by anxiety.     

Comparative study of the psychomotor and antistress effects of ritanserin, alprazolam and diazepam in healthy subjects: some trait anxiety-independent responses.

The new potential anxiolytic ritanserin was studied in a double-blind manner vs. alprazolam, diazepam and placebo in 23 healthy subjects. The subjects belonged either to a high anxiety level group or a low anxiety level group, in order to study the effect of the anxiety level on the pharmacodynamic responses. The assessments included cognitive function (memory tests), psychomotor performance [Critical Flicker Fusion (CFF), Choice Reaction Time (CRT)], subjective ratings of alertness and overnight sleep and stress paradigm. Ritanserin (10 mg), alprazolam (0.75 mg), diazepam (10 mg) and placebo were given as single oral doses following a latin square design. Groups were well contrasted on the Cattell anxiety scale and were not overlapping. On no psychometric variable have there been any interactions between the anxiety level and the drug factor. At baseline an anxiety-related difference between the two groups was observed: lower CFF value in the high anxiety group (-1.4 Hz). Both benzodiazepines impaired psychomotor assessment and memory function and increased sleepiness. Ritanserin decreased CFF values without significantly affecting CRT on which nevertheless a trend to impairment was observed. Memory tests, and subjective ratings of alertness were unaffected by ritanserin. A trend to an antistress effect was observed on electrodermogram after ritanserin. Both benzodiazepines decreased central nervous system arousal and memory while ritanserin was inactive except on CFF. Recent data support the hypothesis that 5-HT2 blockers decrease pupil diameter which is a well known covariate of flicker frequency.     

Effects of lorazepam on memory,attention and sedation in man: antagonism by Ro 15-1788

In this study we examined the effects of lorazepam (2.0 mg PO) plus either placebo or one of three doses of the benzodiazepine antagonist Ro 15-1788 (0.3 mg, 1.0 mg or 3.0 mg IV) on measures of memory, attention and sedation. We found that lorazepam impaired verbal secondary memory performance, but also produced subjective and objective sedation; it increased reaction time, reduced critical flicker fusion thresholds and caused subjects to make more errors on a sustained attention task and rate themselves as drowsy. Ro 15-1788 dose dependently blocked the deficit in secondary memory produced by lorazepam, but also showed monotonic dose-related antagonism of its effects on indices of sedation (with the exception of the critical flicker fusion deficit, which was unaffected). These results demonstrate that lorazepam-induced cognitive deficits can be blocked by a benzodiazepine receptor antagonist. They also suggest that the memory deficits produced in this pharmacological model of organic amnesia are not readily dissociated from deficits in attention.     

Rupatadine does not potentiate the CNS depressant effects of lorazepam: randomized, double-blind, crossover, repeated dose, placebo-controlled study

AIM

The main objective was to assess whether benzodiazepine intake when rupatadine plasma concentrations were at steady-state would increase the CNS depressant effects. Rupatadine is a new H₁-antihistamine which also inhibits platelet activating factor (PAF) release and has been shown to be clinically effective at doses of 10 mg.

METHODS

Sixteen healthy young volunteers took part in a crossover, randomized, double-blind, placebo controlled trial comprising two experimental periods (repeated administration for 7 days of rupatadine 10 mg or placebo as single oral daily doses, separated by a washout of 14 days). On days 5 and 7, according to a fully balanced design, a single oral dose of lorazepam 2 mg or placebo was added. CNS effects were evaluated on these days by seven objective tests of psychomotor performance and eight subjective visual analogue scales (VAS) at pre-dose and several times after drug intake. Four treatment conditions were evaluated: placebo, rupatadine 10 mg, lorazepam 2 mg and rupatadine 10 mg + lorazepam 2 mg.

RESULTS

Significant CNS effects, either impairment of psychomotor performance or subjective sedation, were observed when lorazepam was administered, either alone or in combination with steady state concentrations of rupatadine. No significant differences were found between these two conditions. In addition, rupatadine was not different from placebo. All treatments were well tolerated.

CONCLUSION

Repeated doses of rupatadine (10 mg orally) did not enhance the CNS depressant effects of lorazepam (2 mg orally, single dose) either in objective psychomotor tasks or in subjective evaluations.     

The effects of paroxetine, alone and in combination with alcohol on psychomotor performance and cognitive function in the elderly.

Fifteen healthy male volunteers aged over 60 years received acute and repeated doses of paroxetine 20 mg or placebo, and acute doses of lorazepam 1 mg (as a positive internal control) with or without alcohol (0.6 g/kg of body weight) administered openly in a double blind balanced crossover study in which each subject acted as his own control. Psychomotor performance and cognitive function were assessed using a test battery which included critical flicker fusion, choice reaction time, compensatory tracking, Stroop and memory scanning tests. Subjective ratings of mood and sleep were recorded using line analogue rating scales. The pattern of results indicated that paroxetine had little or no effect on most of the test variables, and in some instances (critical flicker fusion thresholds) improved information processing ability. This was in marked contrast to the lorazepam verum which produced sedation and disruption of performance. Paroxetine had a slight antagonistic effect on alcohol induced sedation whereas impairment of performance with lorazepam was potentiated by co-administration of alcohol. The low behavioural toxicity of paroxetine in elderly volunteers has important implications for the pharmacotherapy of depression.     

The cognitive and psychomotor effects of opioid analgesics

Twelve subjects (8 male) took part in a randomised double blind four way crossover design study comparing four treatments: (i) morphine sulphate 10 mg, (ii) morphine sulphate 15 mg, (iii) lorazepam 1 mg (positive control) and (iv) placebo. Cognitive function was assessed using choice reaction time, number vigilance, memory scanning, immediate and delayed word recall, word recognition, picture recognition, critical flicker fusion threshold (CFFT) and subjective measures of alertness, calmness and contentment. Lorazepam produced a marked impairment in the tests of attention and memory. CFFT was reduced from 1–4 h but this only reached significance at 4 hours. The subjective measures suggested impaired alertness but this did not reach significance. The effects of morphine were less dramatic; both doses of morphine produced significant impairment at 1 hour on tests of secondary memory retrieval (delayed word recall and picture recognition sensitivity). CFFT was reduced for the whole observation period (6 h) achieving statistical significance at 4 hours. Morphine 15 mg produced a significant improvement in accuracy on the choice reaction time test at the 2, 4 and 6 h assessments. These results show minimal impairment of cognitive and psychomotor function after single oral doses of morphine and with possible improvement in one test. Further studies are required to examine the effect of repeated doses.