Buspirone as a Candidate Medication for Methamphetamine Abuse

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01843205

Enrollment

Registered

2013-04-30

Start date

2013-04-30

Completion date

2017-03-31

Last updated

2018-02-07

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

Conditions

Methamphetamine Dependence, Methamphetamine Abuse

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.

Interventions

DRUGMethamphetamine

The pharmacodynamic effects of methamphetamine will be determined during placebo and buspirone maintenance.

DRUGPlacebo

The pharmacodynamic effects of placebo methamphetamine will be determined during placebo and buspirone maintenance.

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

* 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

Design outcomes

Primary

Measure	Time frame	Description
Number of Methamphetamine Doses Self-Administered	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

Measure	Time frame	Description
Peak Score on Stimulant Subscale of the Adjective Rating Scale	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.
Peak Ratings of Active, Alert, Energetic on the Visual Analog Scale	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.
Peak Ratings of Any Effect on the Visual Analog Scale	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.
Peak Ratings of Bad Effects on the Visual Analog Scale	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.
Peak Ratings of Euphoric on the Visual Analog Scale	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.
Peak Ratings of Good Effects on the Visual Analog Scale	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.
Peak Ratings of High on the Visual Analog Scale	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.
Peak Ratings of Irregular/Racing Heartbeat on the Visual Analog Scale	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.
Peak Ratings of Like Drug on the Visual Analog Scale	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.
Peak Ratings of Nauseous on the Visual Analog Scale	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.
Peak Ratings of Nervous/Anxious on the Visual Analog Scale	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.
Peak Ratings of Willing to Pay For on the Visual Analog Scale	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.
Peak Score on Sedative Subscale of the Adjective Rating Scale	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.
Peak Ratings of Performance Improved on the Visual Analog Scale	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.
Peak Ratings of Restless on the Visual Analog Scale	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.
Peak Ratings of Rush on the Visual Analog Scale	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.
Peak Ratings of Shaky/Jittery on the Visual Analog Scale	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.
Peak Ratings of Sluggish/Fatigued/Lazy on the Visual Analog Scale	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.
Peak Ratings of Stimulated on the Visual Analog Scale	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.
Peak Ratings of Willing to Take Again on the Visual Analog Scale	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.
Peak Ratings of Talkative/Friendly on the Visual Analog Scale	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.
Peak Diastolic Blood Pressure	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.
Peak Systolic Blood Pressure	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.
Peak Heart Rate	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.
Peak Temperature	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.
Peak Ratings of Performance Impaired on the Visual Analog Scale	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Completing Participants All subjects who completed the study.	8
Total	8

Withdrawals & dropouts

Period	Reason	FG000	FG001
First Treatment (11 Days)	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Completing Participants
Age, Continuous	40.5 years STANDARD_DEVIATION 5.7
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	3 Participants
Region of Enrollment United States	8 participants
Sex: Female, Male Female	1 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 8	0 / 8
other Total, other adverse events	0 / 8	0 / 8
serious Total, serious adverse events	0 / 8	0 / 8

Outcome results

Primary

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.

Time frame: One test per methamphetamine dose level per intervention for each participant over his/her approximate 25 day inpatient admission

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Number of Methamphetamine Doses Self-Administered	Placebo Methamphetamine	1.25 Number of Methamphetamine Doses	Standard Error 1.25
Placebo	Number of Methamphetamine Doses Self-Administered	10 mg Methamphetamine	6.13 Number of Methamphetamine Doses	Standard Error 1.72
Placebo	Number of Methamphetamine Doses Self-Administered	30 mg Methamphetamine	7.88 Number of Methamphetamine Doses	Standard Error 1.42
Buspirone	Number of Methamphetamine Doses Self-Administered	Placebo Methamphetamine	0 Number of Methamphetamine Doses	Standard Error 0
Buspirone	Number of Methamphetamine Doses Self-Administered	10 mg Methamphetamine	4 Number of Methamphetamine Doses	Standard Error 1.78
Buspirone	Number of Methamphetamine Doses Self-Administered	30 mg Methamphetamine	7.5 Number of Methamphetamine Doses	Standard Error 1.64

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 methamphetamine dose under both buspirone and placebo conditions.