Research article summary (published 30 Oct 2003):

Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD.

Full Abstract

OBJECTIVE: Methylphenidate, the most common treatment for attention deficit hyperactivity disorder (ADHD), increases extracellular dopamine in the brain, which is associated with its reinforcing as well as its therapeutic effects. The authors evaluated variables that distinguish these two properties. METHOD: The brain imaging and clinical literatures were analyzed to identify variables that contribute to the abuse liability as well as to the clinical efficacy of methylphenidate. RESULTS: Four variables were identified. 1) Dose--there is a threshold for methylphenidate-induced dopamine increases to be perceived as reinforcing and to produce therapeutic effects. 2) Pharmacokinetics--the reinforcing effects of methylphenidate are associated with rapid changes in serum concentrations and presumably fast dopamine increases (as achieved with intravenous injection or insufflation), whereas the therapeutic effects are associated with slowly ascending serum concentrations and presumably smoothly rising dopamine levels (as achieved with oral administration). 3) Individual differences--sensitivity to methylphenidate varies across individuals and sets a threshold for blood and brain levels required for reinforcing effects (drug liking) and for therapeutic effects (symptom reduction). 4) Context--the effects of methylphenidate are modulated by different settings in abuse (rituals of self-administration and powerful conditioning) and in clinical use (external demands of low activity and focused attention). CONCLUSIONS: Reinforcing effects occur when methylphenidate elicits large and fast dopamine increases that mimic those of phasic dopamine cell firing, whereas therapeutic effects occur when methylphenidate elicits slow, steady-state dopamine increases that mimic those of tonic firing. Thus, the characteristics of clinical use (low doses administered orally and titrated for therapeutic effects) constrain methylphenidate's abuse.

Author information

Author/s: Volkow, Nora D (ND); Swanson, James M (JM);

Affiliation: National Institute on Drug Abuse/NIH, 6001 Executive Boulevard, Room 5274-MSC 9581, Bethesda, MD 20892, USA. nv29q(-atsign-)nih.gov

Grants: DA 00280 (Agency:NIDA NIH HHS) ; DA 7092-01 (Agency:NIDA NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; Review

Journal: The American journal of psychiatry (Am J Psychiatry), published in United States. (Language: eng)

Reference: 2003-Nov; vol 160 (issue 11) : pp 1909-18

Dates: Created 2003/11/03; Completed 2004/01/29; Revised 2007/11/14;

PMID: 14594733, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Attention Deficit Disorder with Hyperactivity - drug therapy; metabolism; psychology Brain - drug effects; metabolism; physiology Cocaine - pharmacokinetics Delayed-Action Preparations Dopamine - blood; metabolism; physiology Dopamine Plasma Membrane Transport Proteins Dose-Response Relationship, Drug Extracellular Space - drug effects; metabolism Humans Injections, Intravenous

Injections, Intravenous Membrane Glycoproteins Membrane Transport Modulators Membrane Transport Proteins - antagonists & inhibitors; drug effects; metabolism Methylphenidate - adverse effects; pharmacokinetics; therapeutic use Nerve Tissue Proteins Reinforcement (Psychology) Self Medication - psychology Substance-Related Disorders - blood; etiology; metabolism Treatment Outcome

Associated Chemicals: Delayed-Action Preparations (0) ; Dopamine Plasma Membrane Transport Proteins (0) ; Membrane Glycoproteins (0) ; Membrane Transport Modulators (0) ; Membrane Transport Proteins (0) ; Nerve Tissue Proteins (0) ; Methylphenidate (113-45-1) ; Cocaine (50-36-2) ; Dopamine (51-61-6)

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