Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review.

The term neuroenhancement refers to improvement in the cognitive, emotional and motivational functions of healthy individuals through, inter alia, the use of drugs. Of known interventions, psychopharmacology provides readily available options, such as the anti-dementia drugs, e.g. acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine. Based on a systematic review we found that expectations about the potential of these drugs exceed their actual effects, as has been demonstrated in randomised controlled trials. Both single and repeated dose trials were included in the systematic review, however repeated dose trials have only been conducted for donepezil. In six small trials lasting 14-42 days, the following results emerged: donepezil improved the retention of training on complex aviation tasks and verbal memory for semantically processed words. In one study episodic memory was improved, whereas in others it remained unaffected by donepezil. In a sleep deprivation trial, donepezil reduced the memory and attention deficits resulting from 24h of sleep deprivation. Two studies reported even transient negative effects. Regarding the safety profile of donepezil, these studies found that it was rather well tolerated. In any case, since large longitudinal studies are not available no conclusions can be drawn. Seven small studies about the effects of a single dose of memantine, and one study with a single dose of rivastigmine have been reported. Again, these studies are not adequate to answer our research question. If, as here and elsewhere suggested, the concept of pharmaceutical neuroenhancement is not to be rejected in principle, the decision of healthy individuals to take drugs for the purpose of neuroenhancement should be based on exhaustive information. At the moment, the research that would support or oppose the use of acetylcholinesterase inhibitors and memantine for neuroenhancement by healthy individuals has not yet been performed.