Buspirone as a Candidate Medication for Methamphetamine Abuse

• ClinicalTrials.gov Identifier: NCT01843205
• Recruitment Status: Completed
• First Posted: April 30, 2013
• Results First Posted: February 7, 2018
• Last Update Posted: February 7, 2018
• Sponsor: University of Kentucky
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Craig Rush, University of Kentucky

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Methamphetamine Dependence; Methamphetamine Abuse	Drug: Methamphetamine; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Buspirone as a Candidate Medication for Methamphetamine Abuse
• Study Start Date: April 2013
• Actual Primary Completion Date: March 2017
• Actual Study Completion Date: March 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Number of Methamphetamine Doses Self-Administered [ Time Frame: One test per methamphetamine dose level per intervention for each participant over his/her approximate 25 day inpatient admission ]
   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.

Secondary Outcome Measures :

1. Peak Score on Sedative Subscale of the Adjective Rating Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both bupsirone and placebo conditions.
2. Peak Score on Stimulant Subscale of the Adjective Rating Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 "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.
3. Peak Ratings of "Active, Alert, Energetic" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
4. Peak Ratings of "Any Effect" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
5. Peak Ratings of "Bad Effects" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
6. Peak Ratings of "Euphoric" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
7. Peak Ratings of "Good Effects" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
8. Peak Ratings of "High" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
9. Peak Ratings of "Irregular/Racing Heartbeat" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
10. Peak Ratings of "Like Drug" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
11. Peak Ratings of "Nauseous" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine dose under both buspirone and placebo maintenance conditions. ]
    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.
12. Peak Ratings of "Nervous/Anxious" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
13. Peak Ratings of "Willing to Pay For" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
14. Peak Ratings of "Performance Impaired" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
15. Peak Ratings of "Performance Improved" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
16. Peak Ratings of "Restless" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
17. Peak Ratings of "Rush" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
18. Peak Ratings of "Shaky/Jittery" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
19. Peak Ratings of "Sluggish/Fatigued/Lazy" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
20. Peak Ratings of "Stimulated" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
21. Peak Ratings of "Willing to Take Again" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
22. Peak Ratings of "Talkative/Friendly" on the Visual Analog Scale [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
23. Peak Diastolic Blood Pressure [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
24. Peak Systolic Blood Pressure [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
25. Peak Heart Rate [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.
26. Peak Temperature [ Time Frame: Subjects completed this measure at 15 minute intervals for 2 hours after sampling each methamphetamine 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 methamphetamine dose under both buspirone and placebo conditions.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Kentucky

University of Kentucky Medical Center

Lexington, Kentucky, United States, 40536

Sponsors and Collaborators

University of Kentucky

National Institute on Drug Abuse (NIDA)

  Study Documents (Full-Text)

Documents provided by Craig Rush, University of Kentucky:

Study Protocol and Statistical Analysis Plan  [PDF] February 23, 2017

More Information

• Responsible Party: Craig Rush, Professor, University of Kentucky
• ClinicalTrials.gov Identifier: NCT01843205
• Other Study ID Numbers: R21DA035481 ( U.S. NIH Grant/Contract ); R21DA035481 ( U.S. NIH Grant/Contract )
• First Posted: April 30, 2013
• Results First Posted: February 7, 2018
• Last Update Posted: February 7, 2018
• Last Verified: January 2018

Additional relevant MeSH terms:

Methamphetamine; Central Nervous System Stimulants; Physiological Effects of Drugs; Sympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Uptake Inhibitors