title: From Clinical Application to Cognitive Enhancement: The Example of Methylphenidate.
abstract: Methylphenidate (MPD) is a central nervous system (CNS) stimulant, which belongs to the phenethylamine group and is mainly used in the treatment of attention deficit hyperactive disorder (ADHD). However, a growing number of young individuals misuse or abuse MPD to sustain attention, enhance intellectual capacity and increase memory. Recently, the use of MPD as a cognitive enhancement substance has received much attention and raised concerns in the literature and academic circles worldwide. The prescribing frequency of the drug has increased sharply as consequence of the more accurate diagnosis of the ADHD and the popularity of the drug itself due to its beneficial short-term effect. However, careful monitoring is required, because of possible abuse. In this review different aspects concerning the use of MPD have been approached. Data showing its abuse among college students are given, when the drug is prescribed short term beneficial effects and side effects are provided; moreover studies on animal-models suggesting long lasting negative effects on healthy brains are discussed. Finally, emphasis is given to the available formulations and pharmacology.
authors.affiliation: Department of Anatomical, Histological, Medico-legal and Orthopaedic Sciences, Sapienza University of Rome, Viale Regina Elena 336 (00185) Rome, IT. fra.busardo@libero.it.
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Busardò
authors.forename: Chrystalla
authors.initials: C
authors.lastname: Kyriakou
authors.forename: Luigi
authors.initials: L
authors.lastname: Cipolloni
authors.forename: Simona
authors.initials: S
authors.lastname: Zaami
authors.forename: Paola
authors.initials: P
authors.lastname: Frati
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology
chemical_list: D000697:Central Nervous System Stimulants; D018697:Nootropic Agents; D008774:Methylphenidate
references.citation: J Abnorm Child Psychol. 2012 Jul;40(5):669-81
references.pmid: 22187093
references.citation: Biol Psychiatry. 2005 Jun 1;57(11):1377-84
references.pmid: 15950011
references.citation: Arch Gen Psychiatry. 1995 Jun;52(6):456-63
references.pmid: 7771915
references.citation: Biol Psychiatry. 2012 Aug 1;72(3):221-7
references.pmid: 22209638
references.citation: Arch Gen Psychiatry. 1993 Jul;50(7):565-76
references.pmid: 8317950
references.citation: Pediatrics. 1983 Jul;72(1):56-9
references.pmid: 6866592
references.citation: J Pharmacol Exp Ther. 1983 Aug;226(2):382-6
references.pmid: 6410043
references.citation: J Child Neurol. 1991;6 Suppl:S68-75
references.pmid: 2002217
references.citation: Clin Neuropharmacol. 2010 Jul;33(4):204-6
references.pmid: 20571380
references.citation: J Atten Disord. 2014 Nov 5;:null
references.pmid: 25376193
references.citation: J Child Adolesc Psychopharmacol. 1998;8(1):13-25
references.pmid: 9639076
references.citation: J Pharmacol Exp Ther. 1974 Dec;191(3):535-47
references.pmid: 4473537
references.citation: JAMA. 2000 Feb 23;283(8):1025-30
references.pmid: 10697062
references.citation: Expert Opin Drug Metab Toxicol. 2013 Aug;9(8):1001-14
references.pmid: 23611637
references.citation: Arch Dis Child. 2014 Sep;99(9):866-72
references.pmid: 24748641
references.citation: Am J Psychiatry. 1995 Feb;152(2):298-9
references.pmid: 7840374
references.citation: J Am Acad Child Adolesc Psychiatry. 1996 Oct;35(10):1304-13
references.pmid: 8885584
references.citation: J Child Adolesc Psychopharmacol. 2006 Dec;16(6):687-98
references.pmid: 17201613
references.citation: Biol Psychiatry. 2003 Dec 15;54(12):1317-29
references.pmid: 14675795
references.citation: Rev Neurol. 2012 Sep 16;55(6):359-69
references.pmid: 22972578
references.citation: Curr Neuropharmacol. 2015 Jan;13(1):5-11
references.pmid: 26074739
references.citation: CNS Drugs. 2014 Mar;28(3):217-28
references.pmid: 24532028
references.citation: JAMA. 2011 Dec 28;306(24):2673-83
references.pmid: 22161946
references.citation: Am J Health Syst Pharm. 2014 Jul 15;71(14):1163-70
references.pmid: 24973373
references.citation: Nature. 1995 Aug 17;376(6541):572-5
references.pmid: 7637804
references.citation: Br J Pharmacol. 2006 Jan;147 Suppl 1:S82-8
references.pmid: 16402124
references.citation: Biol Psychiatry. 2003 Dec 15;54(12):1465-8
references.pmid: 14675812
references.citation: J Dev Behav Pediatr. 1997 Aug;18(4):271-9
references.pmid: 9276836
references.citation: N Engl J Med. 1972 Apr 20;286(16):880-1
references.pmid: 5061074
references.citation: Biopharm Drug Dispos. 2000 Jan;21(1):23-31
references.pmid: 11038435
references.citation: J Clin Psychopharmacol. 2008 Jun;28(3 Suppl 2):S46-53
references.pmid: 18480677
references.citation: Dis Nerv Syst. 1960 Jun;21:346-9
references.pmid: 14437533
references.citation: J Pediatr Urol. 2013 Feb;9(1):e1-2
references.pmid: 22552161
references.citation: J Clin Psychiatry. 1998;59 Suppl 7:4-16
references.pmid: 9680048
references.citation: N Engl J Med. 2011 Nov 17;365(20):1896-904
references.pmid: 22043968
references.citation: J Child Adolesc Psychopharmacol. 2009 Dec;19(6):663-71
references.pmid: 20035584
references.citation: Pharmacoepidemiol Drug Saf. 2001 Mar-Apr;10(2):85-94
references.pmid: 11499858
references.citation: Prim Care Companion J Clin Psychiatry. 2000 Oct;2(5):159-164
references.pmid: 15014637
references.citation: Neuropsychopharmacology. 2006 Nov;31(11):2376-83
references.pmid: 16855530
references.citation: Turk J Pediatr. 2009 Sep-Oct;51(5):478-84
references.pmid: 20112604
references.citation: Hum Psychopharmacol. 2004 Apr;19(3):151-80
references.pmid: 15079851
references.citation: Biol Psychiatry. 2006 Nov 15;60(10):1111-20
references.pmid: 16806100
references.citation: Child Psychiatry Hum Dev. 2009 Sep;40(3):353-66
references.pmid: 19280339
references.citation: J Subst Abuse Treat. 2015 Apr;51:82-90
references.pmid: 25491733
references.citation: J Clin Pharmacol. 2000 Oct;40(10):1141-9
references.pmid: 11028253
references.citation: Psychiatry Res. 2009 Apr 30;166(2-3):210-22
references.pmid: 19285351
references.citation: Atten Defic Hyperact Disord. 2010 Dec;2(4):241-55
references.pmid: 21258430
references.citation: Acta Psychiatr Scand. 2012 Feb;125(2):114-26
references.pmid: 22118249
references.citation: Postgrad Med. 2014 Sep;126(5):64-81
references.pmid: 25295651
references.citation: Clin Biochem. 1980 Dec;13(6):266-72
references.pmid: 7214694
references.citation: Neuropsychopharmacology. 2002 Nov;27(5):699-711
references.pmid: 12431845
references.citation: J Fam Pract. 2004 Aug;53(8):659-61
references.pmid: 15298843
references.citation: Neural Plast. 2004;11(1-2):97-114
references.pmid: 15303308
references.citation: Child Adolesc Psychiatry Ment Health. 2014 Dec 31;8(1):273
references.pmid: 25606052
references.citation: Turk J Pediatr. 2010 Jul-Aug;52(4):430-4
references.pmid: 21043394
references.citation: J Am Acad Child Adolesc Psychiatry. 2004 Mar;43(3):260-8
references.pmid: 15076258
references.citation: NIH Consens Statement. 1998 Nov 16-18;16(2):1-37
references.pmid: 10868163
references.citation: Drug Saf. 1997 Sep;17(3):143-8
references.pmid: 9306050
references.citation: J Am Acad Child Adolesc Psychiatry. 1991 Sep;30(5):773-5
references.pmid: 1938793
references.citation: CNS Drugs. 2006;20(9):713-38
references.pmid: 16953648
references.citation: J Am Coll Health. 2006 Mar-Apr;54(5):261-8
references.pmid: 16539218
references.citation: Psychosom Med. 1957 Jan-Feb;19(1):38-49
references.pmid: 13400991
references.citation: Pediatrics. 1996 Dec;98(6 Pt 1):1084-8
references.pmid: 8951257
references.citation: J Neurosci. 2000 Mar 15;20(6):RC65
references.pmid: 10704519
references.citation: Eur Neuropsychopharmacol. 2011 Feb;21(2):192-204
references.pmid: 21146374
references.citation: Mayo Clin Proc. 2000 Jul;75(7):711-21
references.pmid: 10907387
references.citation: J Am Coll Health. 2000 Nov;49(3):143-5
references.pmid: 11125642
references.citation: Child Neuropsychol. 2004 Sep;10(3):155-61
references.pmid: 15590494
references.citation: J Clin Psychiatry. 1998;59 Suppl 7:42-9
references.pmid: 9680052
references.citation: BMC Psychiatry. 2013;13:237
references.pmid: 24074240
references.citation: Arch Intern Med. 1991 Apr;151(4):781-3
references.pmid: 1849397
references.citation: Clin Pract Epidemiol Ment Health. 2007 Oct 20;3:21
references.pmid: 17949504
references.citation: Sleep. 2005 Jun;28(6):667-72
references.pmid: 16477952
references.citation: J Med Ethics. 2010 Apr;36(4):198-202
references.pmid: 20338928
references.citation: JAMA Psychiatry. 2013 Feb;70(2):185-98
references.pmid: 23247506
references.citation: Eur Arch Psychiatry Clin Neurosci. 2014 Nov;264 Suppl 1:S83-90
references.pmid: 25214391
references.citation: PLoS One. 2012;7(12):e51910
references.pmid: 23284812
references.citation: J Pharmacol Exp Ther. 1999 Oct;291(1):409-15
references.pmid: 10490931
references.citation: J Am Geriatr Soc. 2012 Feb;60(2):296-303
references.pmid: 22283516
references.citation: Acta Med Iran. 2014;52(9):675-80
references.pmid: 25325205
references.citation: J Am Acad Child Adolesc Psychiatry. 2010 Oct;49(10):1011-23
references.pmid: 20855046
references.citation: Drug Metab Dispos. 1982 Nov-Dec;10(6):708-9
references.pmid: 6130929
references.citation: Behav Brain Funct. 2005 Apr 22;1(1):2
references.pmid: 15916700
references.citation: CNS Drugs. 2011 Jul;25(7):539-54
references.pmid: 21699268
references.citation: Pharmacotherapy. 2006 Oct;26(10):1501-10
references.pmid: 16999660
references.citation: J Neurochem. 2011 Jan;116(2):164-76
references.pmid: 21073468
references.citation: Psychiatry (Edgmont). 2010 Apr;7(4):13-5
references.pmid: 20508803
references.citation: J Am Acad Child Adolesc Psychiatry. 1996 Nov;35(11):1421
references.pmid: 8936903
references.citation: Arch Pediatr Adolesc Med. 2002 Mar;156(3):217-24
references.pmid: 11876664
references.citation: J Dual Diagn. 2014;10(1):32-8
references.pmid: 25392060
references.citation: Optom Clin. 1992;2(4):73-96
references.pmid: 1363080
references.citation: J Am Acad Child Adolesc Psychiatry. 2001 Feb;40(2):188-96
references.pmid: 11211367
references.citation: Behav Brain Res. 2015 Mar 15;281:116-24
references.pmid: 25496784
references.citation: Pharmacotherapy. 2003 Oct;23(10):1281-99
references.pmid: 14594346
references.citation: Behav Brain Funct. 2006 Jan 10;2:2
references.pmid: 16403217
references.citation: CNS Drugs. 2014 Nov;28(11):1005-33
references.pmid: 25120227
references.citation: J Clin Psychiatry. 2013 Sep;74(9):902-17
references.pmid: 24107764
references.citation: Eur J Clin Pharmacol. 2015 Feb;71(2):229-36
references.pmid: 25407613
references.citation: CNS Drugs. 2013 Jan;27(1):15-30
references.pmid: 23160939
references.citation: Neuropharmacology. 2009 Sep;57(3):201-7
references.pmid: 19540860
references.citation: J Abnorm Child Psychol. 2008 Aug;36(6):825-37
references.pmid: 18317920
references.citation: Am J Psychiatry. 2007 Jun;164(6):942-8
references.pmid: 17541055
references.citation: Case Rep Pediatr. 2015;2015:437298
references.pmid: 25688317
references.citation: BMC Psychiatry. 2010;10:67
references.pmid: 20815868
references.citation: Psychol Bull. 1997 Jan;121(1):65-94
references.pmid: 9000892
references.citation: J Am Acad Child Adolesc Psychiatry. 2011 Nov;50(11):1129-1139.e2
references.pmid: 22024001
references.citation: Psychopharmacology (Berl). 1999 Sep 1;146(1):93-100
references.pmid: 10485970
references.citation: Neuropsychopharmacology. 2006 Mar;31(3):594-601
references.pmid: 15999146
references.citation: Pharmacotherapy. 2003 May;23(5):609-17
references.pmid: 12741435
references.citation: J Med Chem. 1981 Oct;24(10):1237-40
references.pmid: 7328584
references.citation: Drug Metab Dispos. 1981 Sep-Oct;9(5):415-23
references.pmid: 6117439
references.citation: Expert Rev Neurother. 2013 Sep;13(9):979-88
references.pmid: 24053342
references.citation: J Child Adolesc Psychopharmacol. 2012 Dec;22(6):423-431
references.pmid: 23362511
references.citation: J Clin Pharmacol. 1998 Mar;38(3):276-82
references.pmid: 9549666
references.citation: J Clin Psychiatry. 1998;59 Suppl 7:76-9
references.pmid: 9680056
references.citation: J Child Adolesc Psychopharmacol. 2009 Aug;19(4):329-39
references.pmid: 19702485
references.citation: N Engl J Med. 1971 Aug 19;285(8):464
references.pmid: 5557291
references.citation: Arch Gen Psychiatry. 2007 Feb;64(2):218-24
references.pmid: 17283289
references.citation: J Clin Pharmacol. 2000 Apr;40(4):379-88
references.pmid: 10761165
references.citation: Biol Psychiatry. 2012 Nov 15;72(10):880-8
references.pmid: 22609367
references.citation: J Anal Toxicol. 1986 Sep-Oct;10(5):209-10
references.pmid: 3773482
references.citation: Ann Pharmacother. 2014 Oct;48(10):1350-5
references.pmid: 24982313
references.citation: JAMA. 1971 Aug 23;217(8):1079-81
references.pmid: 5109429
references.citation: J Am Acad Child Adolesc Psychiatry. 1988 Jan;27(1):88-9
references.pmid: 3343212