n-Acetylcysteine and Cocaine

Motivation for Cocaine and Non-Drug Reinforcers: Targeting Glutamate Homeostasis

This study will determine the initial efficacy, safety and tolerability of n-acetylcysteine as a pharmacotherapy for cocaine dependence. A rigorous, inpatient human laboratory study will be conducted in which the subjective, physiological and reinforcing effects of cocaine are evaluated during maintenance on placebo and n-acetylcysteine.

Study Overview

• Status: Completed
• Conditions: Cocaine Dependence; Cocaine Abuse
• Intervention / Treatment: Drug: Placebo; Drug: Cocaine; Drug: n-Acetylcysteine

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40507
      • University of Kentucky Laboratory of Human Behavioral Pharmacology

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:

• Current cocaine use
• Current cigarette smoker

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 n-acetylcysteine
• History of schizophrenia in first degree relative

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 oral placebo.	Drug: Placebo; Drug: Cocaine; The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and n-acetylcysteine.
Experimental: n-Acetylcysteine; Subjects will be maintained on oral n-acetylcysteine.	Drug: Cocaine; The pharmacodynamic effects of cocaine will be determined during maintenance on placebo and n-acetylcysteine.; Drug: n-Acetylcysteine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	One test per cocaine dose level per intervention for each participant over his/her approximate 2 week 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 "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 n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	Subjects completed this measure at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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 cocaine dose under both n-acetylcysteine and placebo conditions.	This measure was completed at 15 minute intervals for 45 minutes after sampling each cocaine dose under both n-acetylcysteine 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: May 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 14, 2014
• First Posted (Estimate): May 19, 2014

Study Record Updates

• Last Update Posted (Estimate): January 4, 2017
• Last Update Submitted That Met QC Criteria: November 16, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Antiviral Agents; Sensory System Agents; Anesthetics; Protective Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Anesthetics, Local; Respiratory System Agents; Dopamine Uptake Inhibitors; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Vasoconstrictor Agents; Acetylcysteine; N-monoacetylcystine; Cocaine
• Other Study ID Numbers: R21DA035376 (U.S. NIH Grant/Contract)