Clinical trial NCT01267292: Psychopharmacology for Cocaine Dependence - Buspirone
Official title: Psychopharmacology of Novel Medications for Cocaine Dependence - Buspirone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cocaine Dependence
Keywords: cocaine dependence
psychopharmacology
attentional bias
risky decision making
buspirone
methylphenidate
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2010-12-28
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Primary outcomes:
measure: Attentional Bias as Assessed by Score on the Stroop Task
timeFrame: 1 time a day on Wednesday and Friday of week 2; 1 time a day on Monday and Wednesday of week 3
measure: Risky Decision Making as Assessed by Score on the Risky Decision Making Task
timeFrame: 1 time a day on Wednesday and Friday of week 2; 1 time a day on Monday and Wednesday of week 3
Secondary outcomes:
measure: Subjective Effects as Assessed by the Addiction Research Center Inventory (ARCI)
timeFrame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
measure: Subjective Effects as Assessed by Score on the Vigor Subscale of the Profile of Mood States (POMS)
timeFrame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
measure: Subjective Effects as Assessed by Score on the "Feel High" Subscale of the Drug Effects Questionnaire (DEQ)
timeFrame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
measure: Subjective Effects as Assessed by the "Elated" Subscale of the Visual Analogue Scale (VAS)
timeFrame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
measure: Heart Rate
timeFrame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
measure: Systolic Blood Pressure
timeFrame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
measure: Diastolic Blood Pressure
timeFrame: 11 times a day on Wednesday and Friday of week 2; 11 times a day on Monday and Wednesday of week 3
measure: Rapid Response Inhibition as Assessed by the Immediate Memory Task (IMT)
timeFrame: baseline
measure: Rapid Response Inhibition as Assessed by the Immediate Memory Task (IMT)
timeFrame: Thursday of week 1
measure: Rapid Response Inhibition as Assessed by the Immediate Memory Task (IMT)
timeFrame: Monday of week 4
measure: Reversal Learning as Assessed by Number of Perseverative Errors on the Reversal Learning Task
timeFrame: baseline
measure: Reversal Learning as Assessed by Number of Perseverative Errors on the Reversal Learning Task
timeFrame: Thursday of week 1
measure: Reversal Learning as Assessed by Number of Perseverative Errors on the Reversal Learning Task
timeFrame: Monday of week 4
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Scott D Lane, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: