Behavioral Effects of Drugs (Inpatient): 40 [Methamphetamine, Methylphenidate, Duloxetine]

A Novel Drug Combination as a Pharmacotherapeutic for Methamphetamine-Use Disorder

This study will evaluate the behavioral effects of methamphetamine during maintenance on placebo, duloxetine, methylphenidate and duloxetine combined with methylphenidate using sophisticated human laboratory methods.

Study Overview

• Status: Completed
• Conditions: Methamphetamine Use Disorder
• Intervention / Treatment: Drug: Methamphetamine; Drug: Methylphenidate; Drug: Placebo oral capsule; Drug: Duloxetine

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
    • Lexington, Kentucky, United States, 40507
      • University of Kentucky

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:

• recent use of inhaled (i.e., snorted), smoked or injected methamphetamine

Exclusion Criteria:

• Abnormal screening outcome (e.g., ECG, blood chemistry result) that study physicians deem clinically significant.
• Current or past histories of substance use 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, methylphenidate, or duloxetine.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator: Placebo; Subjects will be maintained on oral placebo. Subjects will be maintained on placebo and methylphenidate during placebo maintenance. Methamphetamine will be administered acutely during placebo maintenance. Placebo will be administered acutely during placebo maintenance.	Drug: Methamphetamine; In each arm, subjects will receive doses of methamphetamine.; Other Names: Metamfetamine; Drug: Methylphenidate; In each arm, subjects will receive methylphenidate capsules.; Other Names: Metadate®; Drug: Placebo oral capsule; In each arm, subjects will receive placebo capsules.; Other Names: Lactose
Active Comparator: Active Comparator: Duloxetine; Subjects will be maintained on oral duloxetine. Subjects will be maintained on duloxetine and methylphenidate during placebo maintenance. Methamphetamine will be administered acutely during duloxetine maintenance. Placebo will be administered acutely during duloxetine maintenance.	Drug: Methamphetamine; In each arm, subjects will receive doses of methamphetamine.; Other Names: Metamfetamine; Drug: Methylphenidate; In each arm, subjects will receive methylphenidate capsules.; Other Names: Metadate®; Drug: Placebo oral capsule; In each arm, subjects will receive placebo capsules.; Other Names: Lactose; Drug: Duloxetine; Subjects will receive duloxetine capsules in the duloxetine arm.; Other Names: Cymbalta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reinforcing Effects of Methamphetamine Following Methylphenidate (0 mg; Placebo) Maintenance.	Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement. Subjects sample a dose of methamphetamine (0, 10, or 20 mg) and then have ten opportunities (e.g., trials) to "work" for a 1/10th of the sampled dose via clicking on a computer mouse (i.e., 10 completed trials is the full sampled dose).	Following at least 4 days of maintenance on placebo during inpatient admission, up to 1 week
Reinforcing Effects of Methamphetamine Following Methylphenidate (20 mg) Maintenance.	Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement. Subjects sample a dose of methamphetamine (0, 10, or 20 mg) and then have the ten opportunities (e.g., trials) to "work" for a 1/10th of the sampled dose via clicking on a computer mouse (i.e., 10 completed trials is the full sampled dose).	Following at least 4 days of maintenance on drug during inpatient admission, up to 1 week
Reinforcing Effects of Methamphetamine Following Methylphenidate (40 mg) Maintenance.	Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement. Subjects sample a dose of methamphetamine (0, 10, or 20 mg) and then have the ten opportunities (e.g., trials) to "work" for a 1/10th of the sampled dose via clicking on a computer mouse (i.e., 10 completed trials is the full sampled dose).	Following at least 4 days of maintenance on drug during inpatient admission, up to 1 week
Reinforcing Effects of Methamphetamine Following Methylphenidate (60 mg) Maintenance.	Number of methamphetamine doses earned by subjects on a progressive ratio schedule of reinforcement. Subjects sample a dose of methamphetamine (0, 10, or 20 mg) and then have the ten opportunities (e.g., trials) to "work" for a 1/10th of the sampled dose via clicking on a computer mouse (i.e., 10 completed trials is the full sampled dose).	Following at least 4 days of maintenance on drug during inpatient admission, up to 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance.	Heart Rate (beats per minute) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Heart Rate After Methamphetamine Administration Following Methylphenidate (20 mg) Maintenance.	Heart Rate (beats per minute) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Heart Rate After Methamphetamine Administration Following Methylphenidate (40 mg) Maintenance.	Heart Rate (beats per minute) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Heart Rate After Methamphetamine Administration Following Methylphenidate (60 mg) Maintenance.	Heart Rate (beats per minute) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Systolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance.	Systolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Systolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (20 mg) Maintenance.	Systolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Systolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (40 mg) Maintenance.	Systolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Systolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (60 mg) Maintenance.	Systolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Diastolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance.	Diastolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Diastolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (20 mg) Maintenance.	Diastolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Diastolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (40 mg) Maintenance.	Diastolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Diastolic Blood Pressure After Methamphetamine Administration Following Methylphenidate (60 mg) Maintenance.	Diastolic blood pressure (millimeter of mercury) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Temperature After Methamphetamine Administration Following Methylphenidate (0 mg) Maintenance.	Oral temperature (degrees fahrenheit) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Temperature After Methamphetamine Administration Following Methylphenidate (20 mg) Maintenance.	Oral temperature (degrees fahrenheit) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Temperature After Methamphetamine Administration Following Methylphenidate (40 mg) Maintenance.	Oral temperature (degrees fahrenheit) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Temperature After Methamphetamine Administration Following Methylphenidate (60 mg) Maintenance.	Oral temperature (degrees fahrenheit) is recorded following administration of methamphetamine. Data are presented as mean peak effect. Peak effect means the highest rated value following administration of methamphetamine (0, 10, and 20 mg)	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (0 mg) Administration Following Methylphenidate (0 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (10 mg) Administration Following Methylphenidate (0 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (20 mg) Administration Following Methylphenidate (0 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (0 mg) Administration Following Methylphenidate (20 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (10 mg) Administration Following Methylphenidate (20 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (20 mg) Administration Following Methylphenidate (20 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (0 mg) Administration Following Methylphenidate (40 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (10 mg) Administration Following Methylphenidate (40 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (20 mg) Administration Following Methylphenidate (40 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (0 mg) Administration Following Methylphenidate (60 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (10 mg) Administration Following Methylphenidate (60 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.
Subjective Effects of Methamphetamine (20 mg) Administration Following Methylphenidate (60 mg) Maintenance.	Subjective effects (i.e., mood) of methamphetamine are recorded following administration. Data are presented as mean peak effect. Peak effect means the highest rated value (0 - 100 mm) following administration of methamphetamine.	Daily over approximately 1 week of inpatient stay.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Attentional Bias	Subjects will complete an attentional bias task. The number of inhibitory failures (i.e., commission errors) to "no-go" targets following methamphetamine-related stimuli will be used to evaluate attentional bias (range 0 - 1: greater values represent greater number of errors committed). Commission errors are when you response (i.e., press the corresponding key on a computer) when you were instructed not to respond.	12 sessions over approximately 4.5 weeks
Snaith-Hamilton-Pleasure Scale to Measure Anhedonia (Inability to Experience Pleasure)	A 14-item Snaith-Hamilton-Pleasure Scale covers four domains of pleasure response (interest/pastimes, social interaction, sensory experience and food/drink) with higher scores representing less anhedonia. Scores range from 0 to 56 units: lower scores representing greater anhedonia.	4 times over approximately 4.5 weeks
Delay Discounting for Methamphetamine	Subjects will complete a delay discounting task in 4 sessions following 4 days of medication maintenance. Subjects are presented a series of hypothetical choices between a smaller amount of methamphetamine offered "now" or a larger amount of methamphetamine offered a later times in the future (e.g., 4 hours, a day, 3 weeks). The discounting rate, 'k', is calculated and log10-transformed. Greater values of log-transformed 'k' correspond with greater rates of discounting (i.e., preference for smaller reinforcer provided now rather than larger, delayed reinforcers [e.g., smaller amount of methamphetamine given now as opposed to a larger amount given later]). The units for discounting rates are theoretical and not linked to a physical dimension (e.g., number of button presses) and the range is theoretically not bound (i.e., negative infinity to positive infinity).	4 sessions over approximately 4.5 weeks
Delay Discounting for Money	Subjects will complete a delay discounting task in 4 sessions following 4 days of medication maintenance. Subjects are presented a series of hypothetical choices between a smaller sum of money offered "now" or a larger sum of money offered a later times in the future (e.g., 4 hours, a day, 3 weeks). The discounting rate, 'k', is calculated and log10-transformed. Greater values of log-transformed 'k' correspond with greater rates of discounting (i.e., preference for smaller reinforcer provided now rather than larger, delayed reinforcers [e.g., smaller sum of money given now as opposed to a larger sum given later]). The units for discounting rates are theoretical and not linked to a physical dimension (e.g., number of button presses) and the range is theoretically not bound (i.e., negative infinity to positive infinity).	4 sessions over approximately 4.5 weeks

Collaborators and Investigators

• Sponsor: Craig Rush
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): May 5, 2021
• Study Completion (Actual): May 5, 2021

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: November 25, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Antidepressive Agents; Methylphenidate; Psychotropic Drugs; Dopamine Agents; Methamphetamine; Neurotransmitter Agents; Vasoconstrictor Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Stimulants; Duloxetine Hydrochloride; Dopamine Uptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Membrane Transport Modulators
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Duloxetine Hydrochloride; Methylphenidate; Methamphetamine
• Other Study ID Numbers: BED(IN):40; R01DA047391 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No