Psychopharmacology for Cocaine Dependence - Buspirone
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Intervention: Buspirone; Placebo for Buspirone; Methylphenidate; Placebo for Methylphenidate
Intervention description: [week 1: Buspirone 30 mg twice a day (9am and 6pm) on Monday through Sunday] [weeks 2-3: Buspirone 45 mg twice a day (9am and 6pm) on Monday through Sunday]; [week 1: Placebo for Buspirone twice a day (9am and 6pm) on Monday through Sunday] [weeks 2-3: Placebo for Buspirone twice a day (9am and 6pm) on Monday through Sunday]; Methylphenidate serves as an acute stimulant challenge. [week 1: no Methylphenidate or Methylphenidate placebo] [week 2: 0mg Methylphenidate (placebo for Methylphenidate) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)] [week 3: Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)]; [week 1: no Methylphenidate or Methylphenidate placebo] [week 2: 0mg Methylphenidate (placebo for Methylphenidate) on Monday at 10am; Methylphenidate once a day (10am) on Wednesday and Friday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)] [week 3: Methylphenidate once a day (10am) on Monday and Wednesday, and on each of these 2 days the Methylphenidate dose will be different (15 mg, 30mg, 60 mg, or 0mg)]
Intervention MeSH terms: Buspirone; Methylphenidate
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: cocaine dependence; psychopharmacology; attentional bias; risky decision making; buspirone; methylphenidate

Summary:

      Chronic cocaine use may produce disruption of neurotransmitter functions (including
      dopamine). This may in turn contribute to measurable dysfunction in important cognitive and
      behavioral processes. Stimulants that enhance dopamine (DA) function may help in treating
      cocaine dependence and improving behavioral function -- supporting the notion that these
      processes are related. An important step is to understand the subjective, physiological, and
      behavioral effects of potential medications for cocaine dependence.

      DA-modulating drugs may be targets for pharmacotherapy for substance dependence, and
      particularly for stimulant drugs like cocaine, which disrupt normal DA function. Buspirone is
      currently the only available dopamine subtype 3 (DA3) approved for human administration, and
      is thus a viable investigational compound.

      This project proposes to evaluate the DA-modulating effects of buspirone on behavioral
      deficiencies related to DA depletion. Accordingly, the project aims to characterize the
      effects of buspirone in individuals with cocaine dependence. Employing a daily dosing designs
      within an acute stimulant challenge (methylphenidate), the experiment will characterize the
      subjective effects, cardiovascular effects, and behavioral effects (attentional bias to drug
      cues and risky decision making). The primary hypotheses are that buspirone will attenuate the
      increases in subjective drug effects ("stimulated", "like drug") and behavioral effects
      (increases in attentional bias and risky decision making) that are produced by acute
      methylphenidate administration.
    

Eligibility criteria:

        Inclusion Criteria:

          -  cocaine dependent subjects, non-treatment seeking

          -  meet current DSM-IV criteria for cocaine dependence disorder

          -  report using cocaine within the past 30 days

          -  at least 1 positive urine toxicology screen for the cocaine metabolite benzoylecgonine
             (BE) [300 ng/mL, during the initial (2-4 day) screening period

          -  acceptable health on the basis of interview, medical history, and physical exam

          -  able to understand the consent form and provide written informed consent.

        Exclusion Criteria:

          -  currently dependent on any psychoactive substance other than cocaine or nicotine

          -  current DSM-IV diagnosed major psychiatric disorder (e.g., psychosis, bipolar, major
             depressive disorder)

          -  any medical condition that would contraindicate administration of medications

          -  taking medications known to have significant drug interactions study medications

          -  probation / parole requiring reports of drug use to court officers

          -  pregnant or nursing for female patients

          -  cannot read, write, or speak English.