title: Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence.
abstract: BACKGROUND
  Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH), as this stimulant possesses pharmacobehavioral properties similar to those of cocaine.
  
  
  OBJECTIVE
  To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence.
  
  
  METHODS
  We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature.
  
  
  RESULTS
  MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and open-label studies, the results of randomized controlled trials have been disappointing so far and do not corroborate the use of MPH as a substitute for cocaine dependence in patients without attention deficit hyperactivity disorder.
  
  
  CONCLUSIONS
  Clinical studies evaluating MPH substitution for cocaine dependence have provided inconsistent findings. However, the negative findings may be explained by specific study characteristics, among them dosing, duration of treatment, or sample size. This needs to be considered when discussing the potential of MPH as replacement therapy for cocaine dependence. Finally, based on the results, we suggest possible directions for future research.
authors.affiliation: Center for Addictive Disorders, Psychiatric University Clinics Basel, Basel, Switzerland ; Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Dürsteler
authors.affiliation: Center for Addictive Disorders, Psychiatric University Clinics Basel, Basel, Switzerland.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Berger
authors.affiliation: Center for Addictive Disorders, Psychiatric University Clinics Basel, Basel, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Strasser
authors.affiliation: Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caflisch
authors.affiliation: Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Jochen
authors.initials: J
authors.lastname: Mutschler
authors.affiliation: Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Herdener
authors.affiliation: Center for Addictive Disorders, Psychiatric University Clinics Basel, Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Vogel
keywords: agonist replacement; dependence; substitution