Buspirone as a Candidate Medication for Methamphetamine Abuse

Methamphetamine use disorders are an unrelenting public health concern. Intensive research efforts have yielded behavioral interventions that reduce methamphetamine 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 methamphetamine. These preliminary data will be used to support further research developing buspirone as a pharmacotherapy for methamphetamine use disorders. The investigators hypothesize that buspirone will attenuate the reinforcing effects of methamphetamine.

Study Overview

• Status: Completed
• Conditions: Methamphetamine Dependence; Methamphetamine Abuse
• Intervention / Treatment: Drug: Methamphetamine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Lifetime methamphetamine 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 methamphetamine or buspirone

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects will be maintained on placebo.	Drug: Methamphetamine; The pharmacodynamic effects of methamphetamine will be determined during placebo and buspirone maintenance.; Drug: Placebo; The pharmacodynamic effects of placebo methamphetamine will be determined during placebo and buspirone maintenance.
Experimental: Buspirone; Subjects will be maintained on buspirone.	Drug: Methamphetamine; The pharmacodynamic effects of methamphetamine will be determined during placebo and buspirone maintenance.; Drug: Placebo; The pharmacodynamic effects of placebo methamphetamine will be determined during placebo and buspirone maintenance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Methamphetamine Doses Self-Administered	The reinforcing effects of methamphetamine will be determined during placebo and buspirone treatment using a modified progressive ratio procedure in which subjects are offered the opportunity to earn previously sampled doses of methamphetamine. Each ratio completed on the task will earn 1/10th of the sampled dose.	One test per methamphetamine dose level per intervention for each participant over his/her approximate 25 day inpatient admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Score on Sedative Subscale of the Adjective Rating Scale	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 methamphetamine dose under both bupsirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Score on Stimulant Subscale of the Adjective Rating Scale	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 "stimulant" 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 methamphetamine dose under both bupsirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Any Effect" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Bad Effects" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Euphoric" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Good Effects" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "High" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Irregular/Racing Heartbeat" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Like Drug" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Nauseous" on the Visual Analog Scale	Subjects rated their feelings of "Nauseous" 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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Nervous/Anxious" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Willing to Pay For" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Performance Impaired" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Performance Improved" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Restless" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Rush" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Shaky/Jittery" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Sluggish/Fatigued/Lazy" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Stimulated" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Willing to Take Again" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Ratings of "Talkative/Friendly" on the Visual Analog Scale	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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Systolic Blood Pressure	Systolic blood pressure was measured with an automated monitor. Higher values represent greater systolic pressure. Peak scores were calculated from multiple assessments for each methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
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 methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.
Peak Temperature	Oral temperature was measured with an automated monitor. Higher values represent greater temperature. Peak scores were calculated from multiple assessments for each methamphetamine dose under both buspirone and placebo conditions.	Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions.

Collaborators and Investigators

• Sponsor: University of Kentucky
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: April 22, 2013
• First Submitted That Met QC Criteria: April 25, 2013
• First Posted (Estimate): April 30, 2013

Study Record Updates

• Last Update Posted (Actual): February 7, 2018
• Last Update Submitted That Met QC Criteria: January 9, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Methamphetamine
• Other Study ID Numbers: R21DA035481 (U.S. NIH Grant/Contract)