central nervous system stimulants


Summary: A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here.

Top Publications

  1. Coghill D, Banaschewski T, Zuddas A, Pelaz A, Gagliano A, Doepfner M. Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies. BMC Psychiatry. 2013;13:237 pubmed publisher
    ..Further studies are necessary to provide guidance in clinical practice, particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response. ..
  2. Childress A, Sallee F. The use of methylphenidate hydrochloride extended-release oral suspension for the treatment of ADHD. Expert Rev Neurother. 2013;13:979-88 pubmed publisher
    ..The pharmacokinetic, efficacy and safety profiles of this controlled substance are reviewed. ..
  3. Rosas Hernández H, Cuevas E, Lantz S, Ali S, Gonzalez C. Prolactin protects against the methamphetamine-induced cerebral vascular toxicity. Curr Neurovasc Res. 2013;10:346-55 pubmed
    ..These data suggest that PRL protects brain endothelial cells against the Meth-induced toxicity. Further investigation is required to study the mechanisms involved and to confirm these effects in vivo. ..
  4. Adler L, Dirks B, Deas P, Raychaudhuri A, Dauphin M, Lasser R, et al. Lisdexamfetamine dimesylate in adults with attention-deficit/ hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013;74:694-702 pubmed publisher
  5. Singh I, Filipe A, Bárd I, Bergey M, Baker L. Globalization and cognitive enhancement: emerging social and ethical challenges for ADHD clinicians. Curr Psychiatry Rep. 2013;15:385 pubmed publisher
    ..Drawing on this literature, we reflect on the importance of ethically informed, ecologically sensitive clinical practices in relation to ADHD diagnosis and treatment. ..
  6. Dopfner M, Ose C, Fischer R, Ammer R, Scherag A. Comparison of the efficacy of two different modified release methylphenidate preparations for children and adolescents with attention-deficit/hyperactivity disorder in a natural setting: comparison of the efficacy of Medikinet(®) retard and Concerta(. J Child Adolesc Psychopharmacol. 2011;21:445-54 pubmed publisher
    ..Children and adolescents may be treated with a lower daily dose of Medikinet retard (which has a similar IR component as Concerta) without resulting in a clinically relevant worse effect during school time. ..
  7. Pasini A, Sinibaldi L, Paloscia C, Douzgou S, Pitzianti M, Romeo E, et al. Neurocognitive effects of methylphenidate on ADHD children with different DAT genotypes: a longitudinal open label trial. Eur J Paediatr Neurol. 2013;17:407-14 pubmed publisher
    ..10/10 DAT allele seems to be associated with an increased expression level of the dopamine transporter and seems to mediate the MPH treatment response in ADHD patients. ..
  8. Brossard Racine M, Shevell M, Snider L, Bélanger S, Majnemer A. Motor skills of children newly diagnosed with Attention Deficit Hyperactivity Disorder prior to and following treatment with stimulant medication. Res Dev Disabil. 2012;33:2080-7 pubmed publisher
    ..The improvement in behaviour was insufficient to resolve motor problems and these children should therefore be targeted for rehabilitation services. ..
  9. Ginsberg Y, Lindefors N. Methylphenidate treatment of adult male prison inmates with attention-deficit hyperactivity disorder: randomised double-blind placebo-controlled trial with open-label extension. Br J Psychiatry. 2012;200:68-73 pubmed publisher
    ..Osmotic-release oral system methylphenidate is an effective treatment for adult male prison inmates with ADHD. ..

More Information


  1. Vila Luna S, Cabrera Isidoro S, Vila Luna L, Juárez Díaz I, Bata García J, Alvarez Cervera F, et al. Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons. Neuroscience. 2012;202:384-95 pubmed publisher
  2. Pizzo A, Karam C, Zhang Y, Yano H, Freyberg R, Karam D, et al. The membrane raft protein Flotillin-1 is essential in dopamine neurons for amphetamine-induced behavior in Drosophila. Mol Psychiatry. 2013;18:824-33 pubmed publisher
    ..Thus, using our assay we are able to translate molecular and cellular findings to a behavioral level and to differentiate in vivo the distinct mechanisms of two psychostimulants. ..
  3. Singh I. Not robots: children's perspectives on authenticity, moral agency and stimulant drug treatments. J Med Ethics. 2013;39:359-66 pubmed publisher
    ..Medical professionals in particular should help children to flourish with stimulant drug treatments, in good and in bad conditions. ..
  4. Hodgkins P, Shaw M, Coghill D, Hechtman L. Amfetamine and methylphenidate medications for attention-deficit/hyperactivity disorder: complementary treatment options. Eur Child Adolesc Psychiatry. 2012;21:477-92 pubmed publisher
  5. Lakic A. Depressive symptoms as a side effect of the sustained release form of methylphenidate in a 7-year-old boy with attention-deficit hyperactivity disorder. Vojnosanit Pregl. 2012;69:201-4 pubmed
    ..Precise drug activity mechanisms responsible for the appearance of these symptoms remains to be explained. ..
  6. Herman L, Shtayermman O, Aksnes B, Anzalone M, Cormerais A, Liodice C. The use of prescription stimulants to enhance academic performance among college students in health care programs. J Physician Assist Educ. 2011;22:15-22 pubmed
    ..The study investigated the specific stimulants being used and the frequency of usage. It also examined the rates of nicotine, alcohol, and drug abuse versus dependence...
  7. Seng K, Fan L, Lee H, Yong W, Goh B, Lee L. Population pharmacokinetics of modafinil and its acid and sulfone metabolites in Chinese males. Ther Drug Monit. 2011;33:719-29 pubmed publisher
    ..A robust population pharmacokinetic model for modafinil and its metabolites was developed for the first time. Based on this model, individualized dosing based on weight is now possible. ..
  8. Schmitt K, Reith M. The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. PLoS ONE. 2011;6:e25790 pubmed publisher
    ..Our findings highlight a mechanistic difference between modafinil and cocaine-like stimulants and further demonstrate that the conformational effects of a given DAT inhibitor influence its phenomenological effects. ..
  9. Habel L, Cooper W, Sox C, Chan K, Fireman B, Arbogast P, et al. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA. 2011;306:2673-83 pubmed publisher
    ..Apparent protective associations likely represent healthy-user bias. ..
  10. Kubas H, Backenson E, Wilcox G, Piercy J, Hale J. The effects of methylphenidate on cognitive function in children with attention-deficit/hyperactivity disorder. Postgrad Med. 2012;124:33-48 pubmed publisher
    ..Implications for medication use and titration, academic achievement, and long-term treatment efficacy are examined. ..
  11. Schelleman H, Bilker W, Kimmel S, Daniel G, Newcomb C, Guevara J, et al. Methylphenidate and risk of serious cardiovascular events in adults. Am J Psychiatry. 2012;169:178-85 pubmed publisher
    ..Although initiation of methylphenidate was associated with a 1.8-fold increase in risk of sudden death or ventricular arrhythmia, the lack of a dose-response relationship suggests that this association may not be a causal one. ..
  12. McCarthy S, Wilton L, Murray M, Hodgkins P, Asherson P, Wong I. The epidemiology of pharmacologically treated attention deficit hyperactivity disorder (ADHD) in children, adolescents and adults in UK primary care. BMC Pediatr. 2012;12:78 pubmed publisher
    ..The aim of this study was to investigate the annual prevalence and incidence of pharmacologically treated ADHD in children, adolescents and adults in UK primary care...
  13. Erreger K, Davis A, Poe A, Greig N, Stanwood G, Galli A. Exendin-4 decreases amphetamine-induced locomotor activity. Physiol Behav. 2012;106:574-8 pubmed publisher
    ..Our findings implicate GLP-1R signaling as a novel modulator of psychostimulant-induced behavior and therefore a potential therapeutic target for psychostimulant abuse...
  14. Dopfner M, Görtz Dorten A, Breuer D, Rothenberger A. An observational study of once-daily modified-release methylphenidate in ADHD: effectiveness on symptoms and impairment, and safety. Eur Child Adolesc Psychiatry. 2011;20 Suppl 2:S243-55 pubmed publisher
    ..Equasym XL(®) was generally well tolerated; only 3.16% of patients permanently discontinued treatment due to adverse events. Equasym XL(®) is effective and well tolerated in daily clinical practice. ..
  15. Toomey S, Sox C, Rusinak D, Finkelstein J. Why do children with ADHD discontinue their medication?. Clin Pediatr (Phila). 2012;51:763-9 pubmed publisher
    ..Improved methods for psychological side effect management, setting realistic medication goals, and assessing therapeutic success are needed. ..
  16. Barner J, Khoza S, Oladapo A. ADHD medication use, adherence, persistence and cost among Texas Medicaid children. Curr Med Res Opin. 2011;27 Suppl 2:13-22 pubmed publisher
    ..Because ADHD can be effectively treated with pharmacotherapy, providers should be proactive in identifying patients with poor adherence and intervene to address barriers to medication adherence and persistence. ..
  17. Zetterqvist J, Asherson P, Halldner L, Langstrom N, Larsson H. Stimulant and non-stimulant attention deficit/hyperactivity disorder drug use: total population study of trends and discontinuation patterns 2006-2009. Acta Psychiatr Scand. 2013;128:70-7 pubmed publisher
    ..From 2006 to 2009, the number of prescriptions dispensed for ADHD drugs increased substantially. The rate of treatment discontinuation in the age interval 15-21 is higher than expected considering the persistence rates of the disorder. ..
  18. Winterstein A, Gerhard T, Kubilis P, Saidi A, Linden S, Crystal S, et al. Cardiovascular safety of central nervous system stimulants in children and adolescents: population based cohort study. BMJ. 2012;345:e4627 pubmed publisher
    To evaluate the cardiac safety of central nervous system stimulants in children and adolescents. Population based retrospective cohort study...
  19. Froehlich T, Epstein J, Nick T, Melguizo Castro M, Stein M, Brinkman W, et al. Pharmacogenetic predictors of methylphenidate dose-response in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2011;50:1129-1139.e2 pubmed publisher
    ..Response Variability in Children with Attention-Deficit/Hyperactivity Disorder (ADHD); http://www.clinicaltrials.gov; NCT01238822. ..
  20. McCarthy S, Wilton L, Murray M, Hodgkins P, Asherson P, Wong I. Persistence of pharmacological treatment into adulthood, in UK primary care, for ADHD patients who started treatment in childhood or adolescence. BMC Psychiatry. 2012;12:219 pubmed publisher
  21. Coletti D, Pappadopulos E, Katsiotas N, Berest A, Jensen P, Kafantaris V. Parent perspectives on the decision to initiate medication treatment of attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2012;22:226-37 pubmed publisher
  22. Rothenberger A, Becker A, Breuer D, Dopfner M. An observational study of once-daily modified-release methylphenidate in ADHD: quality of life, satisfaction with treatment and adherence. Eur Child Adolesc Psychiatry. 2011;20 Suppl 2:S257-65 pubmed publisher
    ..Equasym XL(®) improved QoL compared with prior therapy, and resulted in good medication satisfaction and adherence in drug-naïve and previously treated patients. ..
  23. Hester R, Nandam L, O Connell R, Wagner J, Strudwick M, Nathan P, et al. Neurochemical enhancement of conscious error awareness. J Neurosci. 2012;32:2619-27 pubmed publisher
  24. Smith M, Farah M. Are prescription stimulants "smart pills"? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals. Psychol Bull. 2011;137:717-41 pubmed publisher
    ..In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research. ..
  25. Cooper W, Habel L, Sox C, Chan K, Arbogast P, Cheetham T, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med. 2011;365:1896-904 pubmed publisher
    ..However, the absolute magnitude of such an increased risk would be low. (Funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration.). ..
  26. Volkow N, Wang G, Tomasi D, Kollins S, Wigal T, Newcorn J, et al. Methylphenidate-elicited dopamine increases in ventral striatum are associated with long-term symptom improvement in adults with attention deficit hyperactivity disorder. J Neurosci. 2012;32:841-9 pubmed publisher
    ..It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response. ..
  27. Wilens T, Morrison N, Prince J. An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in adults. Expert Rev Neurother. 2011;11:1443-65 pubmed publisher
    ..The aggregate literature shows that the stimulants and catecholaminergic nonstimulants investigated had a clinically significant beneficial effect on treating ADHD in adults. ..
  28. Stephenson C, Karanges E, McGregor I. Trends in the utilisation of psychotropic medications in Australia from 2000 to 2011. Aust N Z J Psychiatry. 2013;47:74-87 pubmed publisher
  29. Ramsson E, Howard C, Covey D, Garris P. High doses of amphetamine augment, rather than disrupt, exocytotic dopamine release in the dorsal and ventral striatum of the anesthetized rat. J Neurochem. 2011;119:1162-72 pubmed publisher
    ..These data thus describe a mechanistically similar activation of action potential-dependent dopaminergic neurotransmission by AMPH and cocaine in vivo. Moreover, DA efflux appears to be a unique, but secondary, AMPH action. ..
  30. Martins T, Baptista S, Gonçalves J, Leal E, Milhazes N, Borges F, et al. Methamphetamine transiently increases the blood-brain barrier permeability in the hippocampus: role of tight junction proteins and matrix metalloproteinase-9. Brain Res. 2011;1411:28-40 pubmed publisher
    ..Overall, the present data demonstrate that METH transiently increases the BBB permeability in the hippocampus, which can be explained by alterations on TJ proteins and MMP-9. ..
  31. Fredriksen M, Halmøy A, Faraone S, Haavik J. Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: a review of controlled and naturalistic studies. Eur Neuropsychopharmacol. 2013;23:508-27 pubmed publisher
    ..However, more longitudinal studies of long duration should be performed. In addition, the ethical issues involved in performing double blind RCTs of many years duration should be further explored. ..
  32. Cagniard B, Murphy N. Affective taste responses in the presence of reward- and aversion-conditioned stimuli and their relationship to psychomotor sensitization and place conditioning. Behav Brain Res. 2013;236:289-94 pubmed publisher
    ..These studies suggest that conditioned stimuli interact with or modulate the affective experience of ongoing unconditioned stimuli such as tastants, and these may reflect behavioral processes that guide behavior optimally. ..
  33. Wilens T, Bukstein O, Brams M, Cutler A, Childress A, Rugino T, et al. A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2012;51:74-85.e2 pubmed publisher
    ..Clinical trial registration information-Efficacy and Safety of SPD503 in Combination With Psychostimulants; http://www.clinicaltrials.gov; NCT00734578. ..
  34. Herrold A, Voigt R, Napier T. mGluR5 is necessary for maintenance of methamphetamine-induced associative learning. Eur Neuropsychopharmacol. 2013;23:691-6 pubmed publisher
    ..These findings suggest a subtype-specific role of mGluR5 receptors in the maintenance of place preference memory and potential of mGluR5 NAMs as a useful target for Meth addiction therapy...
  35. Inocente C, Arnulf I, Bastuji H, Thibault Stoll A, Raoux A, Reimao R, et al. Pitolisant, an inverse agonist of the histamine H3 receptor: an alternative stimulant for narcolepsy-cataplexy in teenagers with refractory sleepiness. Clin Neuropharmacol. 2012;35:55-60 pubmed publisher
    ..The benefit was maintained after a mean of 13 months. Pitolisant could constitute an acceptable alternative for the treatment of refractory sleepiness in teenagers with narcolepsy. ..
  36. Emilsson B, Gudjonsson G, Sigurdsson J, Baldursson G, Einarsson E, Olafsdottir H, et al. Cognitive behaviour therapy in medication-treated adults with ADHD and persistent symptoms: a randomized controlled trial. BMC Psychiatry. 2011;11:116 pubmed publisher
    ..ACTRN12611000533998 (http://www.ANZCTR.org.au/ACTRN12611000533998.aspx). ..
  37. Urban K, Waterhouse B, Gao W. Distinct age-dependent effects of methylphenidate on developing and adult prefrontal neurons. Biol Psychiatry. 2012;72:880-8 pubmed publisher
    ..Juvenile treatment with MPH may result in long-lasting, potentially permanent, changes to excitatory neuron function in the prefrontal cortex of juvenile rats. ..
  38. Ishisaka M, Kakefuda K, Oyagi A, Ono Y, Tsuruma K, Shimazawa M, et al. Diacylglycerol kinase ? knockout mice exhibit attention-deficit behavior and an abnormal response on methylphenidate-induced hyperactivity. PLoS ONE. 2012;7:e37058 pubmed publisher
    ..Furthermore, the hyporesponsiveness of DGK? KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGK? has a pivotal involvement in ERK regulation in the striatum. ..
  39. Lindemann C, Langner I, Kraut A, Banaschewski T, Schad Hansjosten T, Petermann U, et al. Age-specific prevalence, incidence of new diagnoses, and drug treatment of attention-deficit/hyperactivity disorder in Germany. J Child Adolesc Psychopharmacol. 2012;22:307-14 pubmed publisher
    ..A relatively low percentage of children receives drug treatment in the first year after the initial diagnosis of ADHD. ..
  40. Olfson M, Huang C, Gerhard T, Winterstein A, Crystal S, Allison P, et al. Stimulants and cardiovascular events in youth with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2012;51:147-56 pubmed publisher
    ..This study examined associations between stimulant use and risk of cardiovascular events and symptoms in youth with attention-deficit/hyperactivity disorder and compared the risks associated with methylphenidate and amphetamines...
  41. Zuvekas S, Vitiello B. Stimulant medication use in children: a 12-year perspective. Am J Psychiatry. 2012;169:160-6 pubmed
    ..Important variations related to racial/ethnic background and geographic region persist, thus indicating a substantial heterogeneity in the approach to the treatment of ADHD in U.S. communities. ..
  42. Arcieri R, Germinario E, Bonati M, Masi G, Zuddas A, Vella S, et al. Cardiovascular measures in children and adolescents with attention-deficit/hyperactivity disorder who are new users of methylphenidate and atomoxetine. J Child Adolesc Psychopharmacol. 2012;22:423-431 pubmed
    ..The long-term impact of these medications is unknown. Several clinically meaningless ECG alterations were observed mostly in MPH-treated youth. We therefore suggest evaluating cardiovascular risks at baseline. ..
  43. Lichtenstein P, Halldner L, Zetterqvist J, Sjölander A, Serlachius E, Fazel S, et al. Medication for attention deficit-hyperactivity disorder and criminality. N Engl J Med. 2012;367:2006-14 pubmed publisher
    ..These findings raise the possibility that the use of medication reduces the risk of criminality among patients with ADHD. (Funded by the Swedish Research Council and others.). ..
  44. Franke A, Christmann M, Bonertz C, Fellgiebel A, Huss M, Lieb K. Use of coffee, caffeinated drinks and caffeine tablets for cognitive enhancement in pupils and students in Germany. Pharmacopsychiatry. 2011;44:331-8 pubmed publisher
    ..Although the use of caffeine tablets was found to be smaller than the above-mentioned means, it still indicates a relatively high disposition for using tablets for purposes of CE. ..
  45. Zhang Y, Lu C, Zhang J, Hu L, Song H, Li J, et al. Gender differences in abusers of amphetamine-type stimulants and ketamine in southwestern China. Addict Behav. 2013;38:1424-30 pubmed publisher
    ..These results suggested that the psychiatrists should focus on the mood disorder among females, psychotic disorders among males who abuse ATS and ketamine, and cognitive impairment disorder for the females who abuse ATS and ketamine. ..
  46. Kapitány Fövény M, Kertész M, Winstock A, Deluca P, Corazza O, Farkas J, et al. Substitutional potential of mephedrone: an analysis of the subjective effects. Hum Psychopharmacol. 2013;28:308-16 pubmed publisher
    ..By having similar subjective effects as MDMA and other entactogens, mephedrone seems able to substitute other enactogenic stimulants. ..
  47. Antshel K, Zhang James Y, Faraone S. The comorbidity of ADHD and autism spectrum disorder. Expert Rev Neurother. 2013;13:1117-28 pubmed publisher
    ..There are also several important differences between autism spectrum disorder and ADHD. Treatment strategies for the comorbid condition will also be reviewed. Future areas of research and clinical need will be discussed. ..
  48. Vigliano P, Galloni G, Bagnasco I, Delia G, Moletto A, Mana M, et al. Sleep in children with attention-deficit/hyperactivity disorder (ADHD) before and after 6-month treatment with methylphenidate: a pilot study. Eur J Pediatr. 2016;175:695-704 pubmed publisher
    ..e., psychostimulants, are not clear. What is new: • Our study showed that the 6-month continuous treatment with methylphenidate did not further negatively impact on sleep architecture in children with ADHD. ..
  49. Park S, Kim B, Cho S, Kim J, Shin M, Yoo H, et al. Baseline severity of parent-perceived inattentiveness is predictive of the difference between subjective and objective methylphenidate responses in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2013;23:410-4 pubmed publisher
  50. Zhao Y, Xiong N, Liu Y, Zhou Y, Li N, Qing H, et al. Human dopamine transporter gene: differential regulation of 18-kb haplotypes. Pharmacogenomics. 2013;14:1481-94 pubmed publisher
    ..Furthermore, we have developed the first pathway map for SLC6A3 regulation. These findings provide a framework for understanding complex and variant-dependent regulations of SLC6A3. ..
  51. Bauer C, Negus S, Blough B, Banks M. Cocaine-like discriminative stimulus effects of phendimetrazine and phenmetrazine in rats. Behav Pharmacol. 2016;27:192-5 pubmed publisher
  52. Sayilan Ozgun G, Ozgun E, Tabakcioğlu K, Süer Gökmen S, Eskiocak S, Cakir E. Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells. Balkan Med J. 2017;34:534-539 pubmed publisher
    ..No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels...
  53. Quinn P, Chang Z, Hur K, Gibbons R, Lahey B, Rickert M, et al. ADHD Medication and Substance-Related Problems. Am J Psychiatry. 2017;174:877-885 pubmed publisher
    ..Rather, medication was associated with lower concurrent risk of substance-related events and, at least among men, lower long-term risk of future substance-related events. ..