The effects of low doses of amylobarbitone sodium and diazepam on human performance.

Hart, J; Hill, HM; Bye, CE; Wilkinson, RT; Peck, AW · 1976 · Crossref

DOI: 10.1111/j.1365-2125.1976.tb00606.x

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Summary

This study investigated the impact of low, clinically relevant doses of amylobarbitone sodium (50 and 100 mg) and diazepam (2.5 and 5 mg) on human performance and subjective states. The research was motivated by previous findings that high doses of barbiturates and benzodiazepines impaired performance, while lower doses often showed sporadic or no effects in short-duration tests. The authors hypothesized that longer, more monotonous tasks would reveal impairments similar to those seen in sleep deprivation, providing data more relevant to everyday activities like driving. The experiment employed a double-blind, balanced Latin square design involving twelve healthy volunteers (seven female, five male). Subjects received one of six treatments—two doses of each drug or lactose placebo—weekly over six weeks. Performance was assessed using a battery of tests administered 45 minutes post-administration and repeated after a rest period. Tests included a one-hour auditory vigilance task, short-term memory digit recall, auditory reaction time, visual search, finger tapping, and digit symbol substitution. Subjective effects were measured via analogue scales. Plasma drug concentrations were analyzed at 3 and 6 hours post-dose to assess pharmacokinetic relationships. Results indicated that auditory vigilance was significantly impaired by all active drugs between 45 minutes and 1 hour 45 minutes post-treatment, with the exception of 100 mg amylobarbitone sodium, which instead significantly increased false reports. These effects dissipated by 4–5 hours. Short-term memory impairment was dose-related and significant 1 hour 45 minutes post-treatment for all drugs, also resolving by 5 hours. Simple auditory reaction time was prolonged by the highest doses of both drugs and by 50 mg amylobarbitone sodium up to 5 hours 15 minutes. Digit symbol substitution was impaired by amylobarbitone sodium and 5 mg diazepam. Visual search and tapping tasks showed no significant drug effects. Subjective ratings confirmed mental and motor impairment 2 hours 45 minutes post-treatment, particularly for the 5 mg diazepam dose. No consistent correlation was found between plasma drug levels and performance changes. The study concludes that low doses of amylobarbitone sodium and diazepam impair performance in healthy subjects, specifically in tasks requiring sustained attention without feedback or short-term memory. The findings suggest that brief tests may underestimate drug-induced impairment, as prolonged, monotonous tasks were more sensitive to these effects. The lack of correlation between plasma levels and performance indicates that individual sensitivity varies. These results have implications for understanding the safety of these medications in contexts requiring sustained cognitive function, such as driving or operating machinery.

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