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Our aim was to determine whether acutely administered donepezil would alter mood in volunteers with no such alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This investigation was a double\u2010blind, crossover design study of 15 young, healthy male participants who were allocated in random order to three oral treatments: placebo and 5\u2010mg and 7.5\u2010mg donepezil (doses which exert clinical and acute cognitive effects without considerable peripheral side effects). At the theoretical peak\u2010plasma concentrations of donepezil, volunteers rated how they felt on validated questionnaires, which included various dimensions of subjective feelings. We also assessed changes in brain\u2010derived neurotrophic factor (BDNF), which is increased by donepezil after chronic regimes and is related to modulation of mood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Donepezil significantly increased ratings of vigour and anxiety symptoms (medium effect sizes). No changes in bodily symptoms or BDNF were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Acute donepezil administration in participants with unaltered cholinergic and dopaminergic tone led to positive and negative changes in affect. These results call for further research on the direct mood effects of donepezil. 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