Assessing the abuse potential of methylphenidate in nonhuman and human subjects - A review

Methylphenidate (MPH) is widely used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children, adolescents, and adults. Methyl phenidate is clearly effective for the treatment of ADHD, but there is cont roversy as to whether it has significant abuse potential like other psychos timulants (e.g., D-amphetamine and cocaine). In general, the drug is believ ed to be abused at rates much lower than those for other stimulants. The pr esent review examines studies that investigated the behavioral pharmacologi cal profile of methylphenidate and discusses how results from these studies address its abuse liability. Using MEDLINE search terms methylphenidate, d rug discrimination, reinforcement, self-administration, subjective effects, subject-rated effects, abuse potential, and abuse liability, along with a review of the references from identified articles, 60 studies were located in which the reinforcing, discriminative-stimulus, or subjective effects of methylphenidate were directly assessed in nonhumans or humans. Forty-eight (80.0%) of the studies reviewed indicate that methylphenidate either funct ions in a manner similar to D-amphetamine or cocaine (e.g., functions as a reinforcer, substitutes fully in drug discrimination experiments), or produ ces a pattern of subjective effects suggestive of abuse potential. The resu lts are discussed as they pertain to factors that may account far the appar ent discrepancy in abuse rates between methylphenidate and other stimulants , including characterization of actual abuse rates, defining abuse and misu se, pharmacokinetic factors, and validity of abuse liability assays. (C) 20 01 Elsevier Science inc. All rights reserved.