Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans

Background: Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. Methods: Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800. mg/70. kg), triazolam (0.25, 0.5. mg/70. kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6. h. Results: Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300. mg/70. kg DXM were generally smaller in magnitude than those observed after 0.5. mg/70. kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. Conclusion: The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300. mg/70. kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse.