Agonist Replacement Therapy for Cocaine Dependence
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      Cocaine dependence is a significant public health concern. The proposed research will provide
      important clinical information regarding the efficacy of agonists replacement therapies for
      managing cocaine dependence.
    

Detailed description: 
      Cocaine abuse and dependence continue to be significant public health concerns. The number of
      Americans that used cocaine in the past month, the percentage of 12th-, 10th- and 8th-graders
      that used cocaine in the past year, and the percentage of treatment admissions involving
      cocaine has remained stable in recent years. In 1996, cocaine use cost society over $45
      billion due to medical consequences, lost productivity and crime. Because of the
      public-health concerns and costs associated with its abuse, identifying a pharmacotherapy for
      cocaine dependence is a priority with the National Institute on Drug Abuse (N.I.D.A.). A
      pharmacological adjunct for cocaine dependence has not yet been identified.

      The results of clinical trials suggest that agonist replacement therapies (e.g.,
      d-amphetamine) may be effective for cocaine dependence. Because d-amphetamine reduces cocaine
      use, these clinical findings can be used as a reference to identify human laboratory
      procedures for screening putative pharmacotherapies. Identifying procedures for assessing the
      efficacy of putative pharmacotherapies is important because human laboratory studies can be
      conducted more rapidly and efficiently than clinical trials. The present project has two
      specific aims. The first specific aim is to demonstrate the sensitivity and predictive
      validity of human laboratory procedures commonly used to screen putative pharmacotherapies
      for cocaine dependence. To accomplish this aim, we will conduct two "proof-of-concept"
      studies. We will first demonstrate the safety and tolerability of d-amphetamine-cocaine
      combinations (Exp. 1). We will then demonstrate that d-amphetamine maintenance attenuates the
      reinforcing effects of cocaine (Exp. 2). The ability to attenuate the reinforcing effects of
      cocaine may be an important characteristic of an effective pharmacotherapy. The results of
      these studies will help elucidate the optimal conditions (e.g., dose) under which
      d-amphetamine might be expected to be effective. The second specific aim is to determine the
      efficacy of atomoxetine (Strattera®) as a putative agonist replacement pharmacotherapy for
      cocaine dependence. To accomplish this aim, we will conduct two experiments to determine the
      effects of cocaine during atomoxetine maintenance. We will first demonstrate the safety and
      tolerability of atomoxetine-cocaine combinations (Exp. 3). Finally, we will determine the
      reinforcing effects of intranasal cocaine during atomoxetine maintenance (Exp. 4).
      Atomoxetine, a potent norepinephrine uptake blocker, was chosen for study because its
      pharmacological and behavioral effects overlap to some extent with those of d-amphetamine,
      but it appears to have less abuse potential. Identifying novel agonist replacement therapies
      is important because clinicians may be reluctant to use d-amphetamine because of its abuse
      potential.
    

Intervention name(s): d-Amphetamine; Atomoxetine
Intervention type(s): Drug
Intervention description(s): Dexedrine (0-60 mg/day); Strattera (0-80 mg/day)
Intervention MeSH terms: Amphetamine; Dextroamphetamine; Atomoxetine Hydrochloride
Intervention model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Basic Science
Keywords: Cocaine; Dependence; Pharmacotherapies