Dose effects of triazolam and alcohol on cognitive performance in healthy volunteers.

Kleykamp, Bethea A.; Griffiths, Roland R.; Mintzer, Miriam Z.

doi:10.1037/a0018407

Cited by 44 publications

(42 citation statements)

References 85 publications

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“…These findings are in agreement with other preclinical results on rotarod and loaded grid test performance (Sanger et al, 1996;Voss et al, 2003), and also correspond to findings in humans on body sway, information processing rate, immediate memory, and sustained attention (Kleykamp et al, 2010;van Steveninck et al, 1996;Wilkinson, 1995). Almorexant, on the contrary, showed no effects on forced motor performance in the rat.…”

Section: Discussionsupporting

confidence: 91%

Differential Effects of the Dual Orexin Receptor Antagonist Almorexant and the GABAA-α1 Receptor Modulator Zolpidem, Alone or Combined with Ethanol, on Motor Performance in the Rat

Steiner

Lecourt

Strasser

et al. 2010

Neuropsychopharmacol

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Current insomnia treatments such as γ-aminobutyric acid (GABA) receptor modulators are associated with sedative and muscle-relaxant effects, which increase when drug intake is combined with alcohol. This study compared the novel sleep-enabling compound almorexant (ACT-078573-hydrochloride), a dual orexin receptor antagonist, with the positive GABA(A)-α1 receptor modulator zolpidem. Both compounds were administered alone or in combination with ethanol, and their effects on forced motor performance were determined in Wistar rats upon waking after treatment. To detect substance-induced sedation and myorelaxation, time spent on an accelerating rotating rod (rotarod) and forepaw grip strength were measured. Zolpidem (10, 30, and 100 mg/kg, p.o.) and ethanol (0.32, 1, and 1.5 g/kg, i.p.) dose-dependently decreased rotarod performance and grip strength, whereas almorexant (30, 100, and 300 mg/kg, p.o.) did not. Doses of ethanol (0.32 and 1 g/kg), which were ineffective when administered alone, showed interactions with zolpidem (10 and 30 mg/kg) leading to reduced rotarod performance and grip strength; in contrast, combination of ethanol (0.32 and 1 g/kg) with almorexant (100 and 300 mg/kg) did not reduce performance or grip strength below ethanol alone. We conclude that unlike zolpidem, almorexant does not interfere with forced motor performance or grip strength in the rat, nor does it further increase the sedative effects of ethanol. Our results suggest that the effect of almorexant can be immediately reversed to full alertness like under physiological sleep, and that almorexant is less likely to show strong sedation, excessive myorelaxation, or interaction with alcohol than commonly prescribed hypnotics such as zolpidem.

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Section: Discussionsupporting

confidence: 91%

Differential Effects of the Dual Orexin Receptor Antagonist Almorexant and the GABAA-α1 Receptor Modulator Zolpidem, Alone or Combined with Ethanol, on Motor Performance in the Rat

Steiner

Lecourt

Strasser

et al. 2010

Neuropsychopharmacol

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“…The finding of longer RTs in high dose BZD users was in line with experimental research on short term BZD use and RT [6][7][8][9][10][11] as well as with an observational study which found longer RTs in anxious, high dose BZD users (1.2-4 DDD) than in healthy non-users [14]. However, in the latter study it was unclear, whether prolonged RTs were due to BZD intake or psychopathology.…”

Section: Discussionsupporting

confidence: 75%

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

Manthey

Loenen-Frösch

Giltay

et al. 2014

Br J Clin Pharmacol

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AIMShort term administration of benzodiazepines (BZD) was found to prolong reaction time (RT) in experimental studies. However, studies on long term BZD use did not always adjust for important confounders and showed inconsistent results. We aimed to identify a possible relationship between long term BZD use and RT in BZD users in this large cross-sectional, observational study. METHODSThe RTs of non-users (n = 2404) were compared with low (n = 288), intermediate (n = 74), and high dose BZD users (n = 57) in the Netherlands Study of Depression and Anxiety (NESDA). RTs were obtained from the Implicit Association Test. Analyses were adjusted for sociodemographic characteristics, health indicators, severity of psychopathology and antidepressant use. RESULTSOf the NESDA participants, 419 subjects (14.8%) used BZDs. A higher dose of BZDs was associated with prolonged RTs (P = 0.01). When comparing the different dose groups, the high dose group, but not the low and medium dose groups, had significantly longer RTs than the non-users. CONCLUSIONSTolerance for the RT prolonging effect of relatively high doses of BZDs does not seem to develop. As prolonged RTs can have adverse consequences in daily life, BZDs should be prescribed conservatively at the lowest possible dose. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Short term benzodiazepine (BZD) use prolongs reaction time (RT).• Although the prevalence of long term BZD use is high, it in unclear whether RT is still affected in chronic use. WHAT THIS STUDY ADDS• High dose BZD use is associated with prolonged RTs in chronic users (independent of psychopathology).• Tolerance for the RT prolonging effect of BZDs does not seem to develop at high doses in chronic users.

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“…Beverage was administered in a covered opaque cup and consumed through a straw wrapped with an ALC-soaked band to mask olfactory and gustatory cues. In addition, 2 ml of 95% ALC was added into the straw to mask taste differences between beverages 27 . The order of the six drug conditions (METH 100%/PL, METH 150%/PL, METH 100%/ALC 0.25, METH 100%/ALC 0.50, METH 150%/ALC 0.25, METH 150%/ALC 0.50) followed a fixed, ascending order (as listed above) for the first three participants as a precaution to determine if dosing conditions were safe and tolerated.…”

Section: Methodsmentioning

confidence: 99%

Effects of methadone plus alcohol on cognitive performance in methadone-maintained volunteers

Kleykamp

Vandrey

Bigelow

et al. 2015

The American Journal of Drug and Alcohol Abuse

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Background Methadone maintenance patients (MMP) often abuse other drugs, including alcohol. The combined use of methadone and alcohol could impair performance and daily functioning. Objective To examine the effects of methadone in combination with alcohol, as well as acute increases in methadone, on performance outcomes. Method This double blind, double-dummy, crossover study included 8 opioid dependent participants stabilized on methadone. Participants completed 6 inpatient sessions corresponding to methadone (100% or 150% of daily dose) and beverage (placebo, 0.25 or 0.50 g/kg alcohol). Performance tasks were completed before and after drug administration. Area under the timecourse values were analyzed by a 2 (methadone dose) by 3 (alcohol dose) repeated measures analysis of variance. Results Main effects of methadone were observed for two attention outcomes, suggesting reduced accuracy and slowed responding at an elevated methadone dose. In addition, main effects of alcohol were observed for episodic memory (false alarms and response bias) suggesting more impulsive responding as alcohol dose increased. No robust interactions of methadone and alcohol were observed for any outcome. Conclusions Study findings indicate that an acute increase in methadone (150%) and a moderate dose of alcohol (2–3 drinks) can impair distinct aspects of performance, although no significant interactive effect between methadone and alcohol was found. Future studies with larger sample sizes, larger doses, and more clinically informative tasks could expand on the present findings and further explore the cognitive consequences of concurrent opioid and alcohol use.

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Dose effects of triazolam and alcohol on cognitive performance in healthy volunteers.

Cited by 44 publications

References 85 publications

Differential Effects of the Dual Orexin Receptor Antagonist Almorexant and the GABAA-α1 Receptor Modulator Zolpidem, Alone or Combined with Ethanol, on Motor Performance in the Rat

Differential Effects of the Dual Orexin Receptor Antagonist Almorexant and the GABAA-α1 Receptor Modulator Zolpidem, Alone or Combined with Ethanol, on Motor Performance in the Rat

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

Effects of methadone plus alcohol on cognitive performance in methadone-maintained volunteers

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