Innovative mechanisms of action for pharmaceutical cognitive enhancement: A systematic review
Psychiatry Research. 2015-09-01; 229(1-2): 12-20
DOI: 10.1016/j.psychres.2015.07.006
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1. Psychiatry Res. 2015 Sep 30;229(1-2):12-20. doi: 10.1016/j.psychres.2015.07.006.
Epub 2015 Jul 8.
Innovative mechanisms of action for pharmaceutical cognitive enhancement: A
systematic review.
Fond G(1), Micoulaud-Franchi JA(2), Brunel L(3), Macgregor A(4), Miot S(5), Lopez
R(6), Richieri R(7), Abbar M(8), Lancon C(2), Repantis D(9).
Author information:
(1)Université Paris EST-Créteil, AP-HP, Pôle de Psychiatrie ET d’addictologie des
Hopitaux Universitaires Henri Mondor, INSERM U955, Eq 15 Psychiatrie Génétique,
DHU PE-psy, Fondation Fondamental Fondation de Coopération Scientifique en Santé
Mentale, F-94000 France. Electronic address: .
(2)Pôle Psychiatrie Universitaire, CHU Sainte-marguerite, F-13274 Marseille Cedex
09, France.
(3)Université Paris EST-Créteil, AP-HP, Pôle de Psychiatrie ET d’addictologie des
Hopitaux Universitaires Henri Mondor, INSERM U955, Eq 15 Psychiatrie Génétique,
DHU PE-psy, Fondation Fondamental Fondation de Coopération Scientifique en Santé
Mentale, F-94000 France.
(4)Université Montpellier 1, INSERM 1061, Service Universitaire de Psychiatrie,
CHU Montpellier F-34000, France.
(5)INSERM U952, CNRS UMR 7224, UMPC Univ Paris 06, F-75000 Paris, France.
(6)Université Montpellier 1, INSERM 1061, Centre de Référence National
Narcolepsie Hypersomnie Idiopathique, Unité des Troubles du Sommeil, CHU
Montpellier F-34000, France.
(7)Pôle Psychiatrie Universitaire, CHU Sainte-marguerite, F-13274 Marseille Cedex
09, France; Faculté de Médecine, EA 3279, Laboratoire de Santé Publique, F-13385
Marseille Cedex 05, France.
(8)CHU Carémeau, Université de Nîmes, Nîmes F-31000, France.
(9)Department of Psychiatry, Charité-Universitätsmedizin Berlin, Campus Benjamin
franklin, Eschenallee 3, 14050 Berlin, Germany.
Pharmacological cognitive enhancement refers to improvement in cognitive
functions after drug use in healthy individuals. This popular topic attracts
attention both from the general public and the scientific community. The
objective was to explore innovative mechanisms of psychostimulant’s action, whose
potential effectiveness was assessed in randomized placebo-controlled trials
(RCTs). A systematic review was carried out, using the words “attention”,
“memory”, “learning”, “executive functions”, and “vigilance/wakefulness” combined
to “cognitive enhancer” or “smart drug”. Methylphenidate, amphetamines,
modafinil, nicotine, acetylcholine esterase inhibitors and antidepressants were
extensively studied in previous meta-analyses and were not included in the
present work. Drugs were classified according to their primary mode of action,
namely catecholaminergic drugs (tolcapone, pramipexole, guanfacine), cholinergic
drugs (anticholinergics), glutamatergic drugs (ampakines), histaminergic drugs,
and non-specified (glucocorticoids). Overall, 50 RCTs were included in the
present review. In conclusion, a number of new active drugs were found to improve
some cognitive functions, in particular verbal episodic memory. However the
number of RCTs was limited, and most of the studies found negative results.
Future studies should assess both effectiveness and tolerance of repeated doses
administration, and individual variability in dose response (including baseline
characteristics and potential genetic polymorphisms). One explanation for the
limited number of recent RCTs with new psychostimulants seems to be the ethical
debate surrounding pharmaceutical cognitive enhancement in healthy subjects.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
DOI: 10.1016/j.psychres.2015.07.006
PMID: 26187342 [Indexed for MEDLINE]