Psychopharmacology for Cocaine Dependence - Buspirone
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Chronic cocaine use may produce disruption of monoamine systems (including dopamine). This
      may in turn contribute to measurable dysfunction in important cognitive and behavioral
      processes. Pharmacotherapy with stimulants that enhance dopamine (DA) function has shown
      efficacy in treating cocaine dependence and improving behavioral function -- supporting the
      notion that these processes are related. In the development of novel pharmacotherapies for
      cocaine dependence, an important step is a full characterization of the psychopharmacological
      properties of potential medications for cocaine dependence, including subjective,
      physiological, and behavioral effects. Selective medications may play a key role in the
      modulation of DA neurotransmission by enhancing DA receptor activation.

      The D3 receptor is an autoreceptor that may function to control phasic DA activity and
      mediate sensitization of DA agonists, thus playing a role in conditioning of drugs of abuse
      like cocaine. Growing evidence suggests that D3 receptor antagonists may be targets for
      pharmacotherapy for substance dependence, and particularly for stimulant drugs like cocaine,
      which disrupt normal DA function. Importantly, administration of D3 antagonists may disrupt
      reactivity (attention) to drug cues and attenuate cue-induced craving. Buspirone is currently
      the only available D3 antagonist approved for human administration, and is thus a viable
      investigational compound.

      This project proposes to evaluate the potential pharmacotherapeutic action of the D3
      antagonist buspirone. The DA-modulating effects of buspirone may help with affective and
      behavioral deficiencies related to DA depletion. Accordingly, the project aims to
      characterize the psychopharmacology of buspirone in individuals with cocaine dependence.
      Employing chronic dosing designs within an acute stimulant challenge (methylphenidate), the
      experiment will be conducted using well-established psychopharmacological methods in order to
      characterize the shape and magnitude of chronic pretreatment-mediated change in the
      methylphenidate dose-response curve. Measures will include subjective effects, cardiovascular
      effects, and behavioral effects (attentional bias to drug cues and risky decision making).
      These data will compliment and provide valuable information to clinical trials using these
      agents to treat cocaine dependence.
    

Intervention name(s): Buspirone; Placebo for Buspirone; Methylphenidate; Placebo for Methylphenidate
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): [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)]
Other intervention name(s): Buspar; corn starch; Ritalin; corn starch
Intervention MeSH terms: Buspirone; Methylphenidate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: cocaine dependence; psychopharmacology; attentional bias; risky decision making; buspirone; methylphenidate