Effects of acute ultra-low dose mecamylamine on cognition in adult attention-deficit/hyperactivity disorder (ADHD)

Objective Nicotinic cholinergic stimulation has known beneficial effects in attention-deficit/hyperactivity disorder (ADHD). Mecamylamine is a non-competitive nicotinic antagonist which is reported in several animal studies to have paradoxical positive effects on cognition at ultra-low doses. Comparable studies in humans have not been conducted. The aim of this study was to determine the effects of acute ultra-low doses of mecamylamine on cognition in adult ADHD. Methods Fifteen (6 female) non-smokers with ADHD completed this acute, within Subjects, double blind study of 0.2, 0.5, 1.0 mg of oral mecamylamine and placebo. Behavioral inhibition, recognition memory, and delay aversion were assessed at each dose. Results The 0.5 mg dose of mecamylamine significantly improved recognition memory and reduced tolerance for delay. Mecamylamine increased participant rated irritability and investigator rated restlessness. There were no effects on vital signs or physical side effects. Conclusion This is the first study to find measurable effects of ultra-low closes of mecamylamine in humans. Mecamylamine did not improve core ADHD cognitive symptoms, but significantly improved recognition memory. These effects may represent mixed receptor activity (activation and blockade) at the doses tested. The finding of beneficial effects on memory processes has important clinical implications and further exploration of this effect is warranted. Copyright (C) 2009 John Wiley & Sons, Ltd.