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.


CONCLUSIONS
This is the first study to find measurable effects of ultra-low doses 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.
Potter
Alexandra S
AS
Clinical Neuroscience Research Unit, Department of Psychiatry, College of Medicine, University of Vermont, Burlington, Vermont 05401, USA. Alexandra.Potter@uvm.edu
Ryan
Katherine K
KK
Newhouse
Paul A
PA
D000293:Adolescent; D000339:Affect / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology*; D001519:Behavior / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008568:Memory / Q000187:drug effects; D009483:Neuropsychological Tests; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects; D021641:Recognition, Psychology / Q000187:drug effects; D055815:Young Adult
D018733:Nicotinic Antagonists; D008464:Mecamylamine