Impact of Buspirone Maintenance on the Reinforcing Effects of Cocaine

Human Laboratory Study of the Impact of Buspirone Maintenance on the Reinforcing, Subjective and Performance Effects of Cocaine

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01639157

Enrollment

Registered

2012-07-12

Start date

2012-09-30

Completion date

2014-12-31

Last updated

2016-02-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cocaine Use Disorders

Brief summary

Cocaine use disorders are an unrelenting public health concern. Intensive research efforts have yielded behavioral interventions that reduce cocaine use, however, these interventions are not universally effective and treatment effects diminish over time. Development of a pharmacotherapy that enhances the efficacy of these interventions is a priority for the National Institute on Drug Abuse. This study proposes to determine the impact of buspirone maintenance on self-administration of cocaine and alternative reinforcers. These preliminary data will be used to support further research developing buspirone as a pharmacotherapy for cocaine use disorders. We hypothesize that buspirone will attenuate the reinforcing effects of cocaine and increase the reinforcing effects of alternative reinforcers.

Interventions

DRUGBuspirone

Subjects will be maintained on oral buspirone (10 mg administered 3 times daily) for 6 days each during the study in random order.

DRUGPlacebo

Subjects will be maintained on oral placebo (0 mg administered 3 times daily) for 6 days each during the study in random order.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* Recent cocaine use

Exclusion criteria

* Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant * Current or past histories of substance abuse or dependence that are deemed by the study physicians to interfere with study completion * History of serious physical disease, current physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease, history of seizure or current or past histories of serious psychiatric disorder that in the opinion of the study physician would interfere with study participation will be excluded from participation * Females not currently using effective birth control * Contraindications to cocaine or buspirone

Design outcomes

Primary

Measure	Time frame	Description
Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	One test per cocaine dose level per intervention for each participant over his/her 2 week inpatient admission	The reinforcing effects of cocaine were determined using a modified progressive ratio procedure (Stoops et al., 2010) in which subjects made 6 choices between available each available cocaine dose and money (US$0.25). Reinforcing effects are measured for each cocaine dose during both buspirone and placebo maintenance.

Secondary

Measure	Time frame	Description
Peak Systolic Blood Pressure	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Systolic blood pressure was measured with an automated monitor. Higher values represent greater systolic pressure. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Score on Stimulant Subscale of the Adjective Rating Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects completed 16 items that loaded into the Stimulant Subscale of the Adjective Rating Scale. The items were rated 0-4 on a Likert-type scale and the sum for the 16 sedative items was summed to yield the Stimulant Subscale score. The maximum score for this scale was 64, the minimum was 0. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Active, Alert, Energetic on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Active, Alert, Energetic on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Any Effect on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Any Effect on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Bad Effects on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Bad Effects on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Euphoric on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Euphoric on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Good Effects on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Good Effects on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of High on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of High on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Irregular/Racing Heartbeat on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Irregular/Racing Heartbeat on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Like Drug on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Like Drug on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Nervous, Anxious on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Nervous, Anxious on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Nauseated, Queasy, Sick to Stomach on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Nauseated, Queasy, Sick to Stomach on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Score on Sedative Subscale of the Adjective Rating Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects completed 16 items that loaded into the Sedative Subscale of the Adjective Rating Scale. The items were rated 0-4 on a Likert-type scale and the sum for the 16 sedative items was summed to yield the Sedative Subscale score. The maximum score for this scale was 64, the minimum was 0. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Performance Impaired on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Performance Impaired on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Performance Improved on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Performance Improved on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Restless on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Restless on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Rush on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Rush on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Shaky, Jittery on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Shaky, Jittery on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Sluggish, Fatigued, Lazy on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Sluggish, Fatigued, Lazy on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Stimulated on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Stimulated on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Willing to Take Again on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Willing to Take Again on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Talkative, Friendly on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Talkative, Friendly on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Oral Temperature	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Oral temperature was measured with an automated monitor. Higher values represent greater temperature. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Diastolic Blood Pressure	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Diastolic blood pressure was measured with an automated monitor. Higher values represent greater diastolic pressure. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Heart Rate	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Heart rate was measured with an automated monitor. Higher values represent greater heart rate. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.
Peak Ratings of Willing to Pay For on the Visual Analog Scale	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.	Subjects rated their feelings of Willing to Pay For on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.

Countries

United States

Participant flow

Participants by arm

Arm	Count
All Study Participants Subjects were maintained on oral buspirone (10 mg administered 3 times daily) or placebo for 6 days each during the study in random order.	9
Total	9

Baseline characteristics

Characteristic	All Study Participants
Age, Continuous	39.4 years
Region of Enrollment United States	9 participants
Sex: Female, Male Female	2 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 9	0 / 9
serious Total, serious adverse events	0 / 9	0 / 9

Outcome results

Primary

Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative

The reinforcing effects of cocaine were determined using a modified progressive ratio procedure (Stoops et al., 2010) in which subjects made 6 choices between available each available cocaine dose and money (US$0.25). Reinforcing effects are measured for each cocaine dose during both buspirone and placebo maintenance.

Time frame: One test per cocaine dose level per intervention for each participant over his/her 2 week inpatient admission

Arm	Measure	Group	Value (MEAN)	Dispersion
Buspirone	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	0 mg Cocaine	1.00 Number of Cocaine Choices	Standard Error 0.707
Buspirone	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	15 mg Cocaine	5.56 Number of Cocaine Choices	Standard Error 0.338
Buspirone	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	45 mg Cocaine	5 Number of Cocaine Choices	Standard Error 0.289
Placebo	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	0 mg Cocaine	1.22 Number of Cocaine Choices	Standard Error 0.813
Placebo	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	15 mg Cocaine	5.33 Number of Cocaine Choices	Standard Error 0.441
Placebo	Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative	45 mg Cocaine	4.89 Number of Cocaine Choices	Standard Error 0.455

Secondary

Peak Diastolic Blood Pressure

Diastolic blood pressure was measured with an automated monitor. Higher values represent greater diastolic pressure. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.

Time frame: This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.

Arm	Measure	Group	Value (MEAN)	Dispersion
Buspirone	Peak Diastolic Blood Pressure	0 mg Cocaine	74.3 mmHg	Standard Error 2.1
Buspirone	Peak Diastolic Blood Pressure	15 mg Cocaine	75.1 mmHg	Standard Error 2.5
Buspirone	Peak Diastolic Blood Pressure	45 mg Cocaine	77.6 mmHg	Standard Error 2.7
Placebo	Peak Diastolic Blood Pressure	0 mg Cocaine	73.3 mmHg	Standard Error 3.1
Placebo	Peak Diastolic Blood Pressure	15 mg Cocaine	74.6 mmHg	Standard Error 2.8
Placebo	Peak Diastolic Blood Pressure	45 mg Cocaine	77.6 mmHg	Standard Error 2.4

Secondary

Peak Heart Rate

Heart rate was measured with an automated monitor. Higher values represent greater heart rate. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.

Time frame: This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.

Arm	Measure	Group	Value (MEAN)	Dispersion
Buspirone	Peak Heart Rate	0 mg Cocaine	75.9 beats per minute	Standard Error 3.6
Buspirone	Peak Heart Rate	15 mg Cocaine	79.9 beats per minute	Standard Error 3.8
Buspirone	Peak Heart Rate	45 mg Cocaine	82.8 beats per minute	Standard Error 2.7
Placebo	Peak Heart Rate	0 mg Cocaine	79.7 beats per minute	Standard Error 3.6
Placebo	Peak Heart Rate	15 mg Cocaine	79.6 beats per minute	Standard Error 4.6
Placebo	Peak Heart Rate	45 mg Cocaine	89.3 beats per minute	Standard Error 5.4

Secondary

Peak Oral Temperature

Oral temperature was measured with an automated monitor. Higher values represent greater temperature. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.

Time frame: This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both buspirone and placebo maintenance conditions.

Arm	Measure	Group	Value (MEAN)	Dispersion
Buspirone	Peak Oral Temperature	0 mg Cocaine	98.2 Degrees Fahrenheit	Standard Error 0.1
Buspirone	Peak Oral Temperature	15 mg Cocaine	98.3 Degrees Fahrenheit	Standard Error 0.1
Buspirone	Peak Oral Temperature	45 mg Cocaine	98.1 Degrees Fahrenheit	Standard Error 0.1
Placebo	Peak Oral Temperature	0 mg Cocaine	98.3 Degrees Fahrenheit	Standard Error 0.2
Placebo	Peak Oral Temperature	15 mg Cocaine	98.4 Degrees Fahrenheit	Standard Error 0.2
Placebo	Peak Oral Temperature	45 mg Cocaine	98.4 Degrees Fahrenheit	Standard Error 0.1

Secondary

Peak Ratings of Active, Alert, Energetic on the Visual Analog Scale

Subjects rated their feelings of Active, Alert, Energetic on a Visual Analog Scale. This item was rated from 0 (minimum)-100 (maximum) on a Visual Analog Scale. Higher values represent greater subjective effects on this item. Peak scores were calculated from multiple assessments for each cocaine dose under both buspirone and placebo conditions.