Modafinil for Smoked Cocaine Self-Administration

Modafinil in a Human Laboratory Model of Cocaine Relapse

Modafinil has been reported to reduce cocaine use in a clinical sample of infrequent users (2 days/week), but the effects of modafinil on cocaine self-administration in the laboratory have not been studied. The present study investigated the effects of modafinil maintenance on cocaine self-administration by frequent users (4 days/week) under controlled laboratory conditions. During this 48-day double-blind, crossover design study, the effects of modafinil maintenance (0, 200, and 400mg/day) on response to smoked cocaine (0, 12, 25, and 50 mg) were examined in nontreatment seeking cocaine-dependent individuals (n = 8).

Study Overview

• Status: Completed
• Conditions: Cocaine Dependence
• Intervention / Treatment: Drug: Modafinil 0 mg; Drug: Cocaine 0 mg; Drug: Cocaine 12 mg; Drug: Cocaine 25 mg; Drug: Cocaine 50 mg; Drug: Modafinil 200 mg; Drug: Modafinil 400 mg

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Smokes cocaine
2. Has patterns of smoked cocaine use in terms of frequency and amount which parallel or exceed those administered in the study.
3. Age 21-50.
4. Able to give informed consent, and comply with study procedures.
5. Normal body weight Within normal weight range (for appropriate frame) according to 1983 Metropolitan Weight tables -

Exclusion Criteria:

1. Current seizure disorder, heart disease or a history of serious adverse effects due to cocaine.
2. Dependence on substances (other than cocaine or nicotine) or a history of dependence on alcohol
3. Request for drug treatment
4. Judged to be noncompliant with study protocol.
5. Current use of any psychotropic medication.
6. Clinical laboratory tests outside normal limits that are clinically unacceptable to the study physician (BP > 140/90; BUN, creatinine, LFTs > 3x ULN; hematocrit < 34 for women, < 36 for men; pseudocholinesterase deficiency)
7. History of myocardial infarction or ischemia, clinically significant left ventricular hypertrophy, angina, clinically significant arrhythmia, or mitral valve prolapse
8. Currently meeting DSM-IV criteria for all major psychiatric/psychotic disorders other than transient psychosis due to drug abuse
9. Current parole or probation Self-report during interview -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Modafinil 0mg + Cocaine 0, 12, 25, 50 mg; Participants were maintained on modafinil (0 mg/day) for 15 days, and underwent a dose response of cocaine.	Drug: Modafinil 0 mg; Modafinil (0 mg/day); Drug: Cocaine 0 mg; Cocaine (0 mg/day); Drug: Cocaine 12 mg; Cocaine (12 mg/day); Drug: Cocaine 25 mg; Cocaine (25 mg/day); Drug: Cocaine 50 mg; Cocaine (50 mg/day)
Experimental: Modafinil 200mg + Cocaine 0, 12, 25, 50 mg; Participants were maintained on modafinil (200 mg/day) for 15 days, and underwent a dose response of cocaine.	Drug: Cocaine 0 mg; Cocaine (0 mg/day); Drug: Cocaine 12 mg; Cocaine (12 mg/day); Drug: Cocaine 25 mg; Cocaine (25 mg/day); Drug: Cocaine 50 mg; Cocaine (50 mg/day); Drug: Modafinil 200 mg; Modafinil (200 mg/day)
Experimental: Modafinil 400mg + Cocaine 0, 12, 25, 50 mg; Participants were maintained on modafinil (400 mg/day) for 15 days, and underwent a dose response of cocaine.	Drug: Cocaine 0 mg; Cocaine (0 mg/day); Drug: Cocaine 12 mg; Cocaine (12 mg/day); Drug: Cocaine 25 mg; Cocaine (25 mg/day); Drug: Cocaine 50 mg; Cocaine (50 mg/day); Drug: Modafinil 400 mg; Modafinil (400 mg/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cocaine Self-administration	The number of purchased cocaine doses as a function of cocaine dose and modafinil maintenance condition.	48 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drug Quality Cluster	Visual analogue scale ratings on the 'Drug Quality' cluster as a function of cocaine dose and modafinil maintenance condition. A cluster score was derived by taking the arithmetic average of the items in the cluster. Scores range from 0-100, with higher scores indicating greater agreement with the term. The "Drug Quality Cluster" consisted of three items: "the choice was of high quality"; "the choice was potent"; "I liked the choice" Higher scores indicate increasing agreement with the statement, which would indicate a poorer outcome.	48 days
Heart Rate	Values for heart rate as a function of cocaine dose and modafinil maintenance condition.	48 days

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Margaret Haney, Ph.D., NYS Psychiatric Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: January 24, 2013
• First Submitted That Met QC Criteria: January 24, 2013
• First Posted (Estimate): January 29, 2013

Study Record Updates

• Last Update Posted (Actual): January 9, 2018
• Last Update Submitted That Met QC Criteria: December 11, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: cocaine; self-administration; modafinil; DRD4
• 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; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Anesthetics, Local; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Vasoconstrictor Agents; Wakefulness-Promoting Agents; Modafinil; Cocaine
• Other Study ID Numbers: 5738; R01DA023650 (U.S. NIH Grant/Contract)