MTC: Medications Development for the Treatment of Cannabis Related Disorders

Sponsor

University of Virginia (Other)

Overall Status

Completed

CT.gov ID

NCT01204723

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Locations

Arms

Duration (Months)

31.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this application is to test the neurobehavioral mechanisms and effects of aprepitant as a new cessation agent for cannabis, tobacco or both.

Condition or Disease	Intervention/Treatment	Phase
Nicotine Withdrawal Marijuana Dependence Cannabis Dependence Nicotine Dependence Cannabis Abuse	Drug: Placebo Aprepitant Drug: Active Aprepitant	Phase 1

Detailed Description

Stress (emotional, physical, social) facilitates drug seeking behavior through the activation of the HPA axis, autonomic nervous system, and brain DA systems. Furthermore, alterations within several neuropeptide systems (CRF, Substance P, and others) also contribute to the role of stress in addiction. Central to this project is that anxiety and stress responses are modulated by substance P and its preferred target, the NK1 receptor. Therefore the aim of this pilot clinical trial is to determine the safety and efficacy of aprepitant (a neurokinin 1 (NK1) receptor antagonist). We hypothesize that the NK1 receptor antagonist, aprepitant, will be safe, tolerable and efficacious at reducing the withdrawal symptoms, cue craving, and reinforcement value for both cannabis and tobacco resulting from the cessation of either or both drugs. We will assess this hypothesis in the context of a carefully controlled human laboratory study in which subjects (N=72) will be randomized in a 3 x 2 factorial design to one of 3 behavioral conditions; a) withdrawn from both substances, b) withdrawn from tobacco only, or c) withdrawn from cannabis only, and to receive one of 2 medication dose conditions: placebo or aprepitant (160 mg/day). Medication will be administered for 5 days, followed by a cue challenge, choice procedure, and then a consequence (i.e., oral cannabis or a cigarette or money) also on day 5.

Study Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Medications Development for the Treatment of Cannabis Related Disorders

Study Start Date :

Aug 1, 2009

Actual Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Behavioral Condition 1 Nicotine patch (21 mg) plus placebo oral cannabis (0 mg; 3 times a day on days 2-4, given once on day 5)	Drug: Placebo Aprepitant Placebo Aprepitant 0 mg once daily for 5 days Drug: Active Aprepitant Active Aprepitant 160 mg once daily for 5 days
Experimental: Behavioral Condition 2 Placebo nicotine patch (0 mg) plus oral cannabis (10 mg, 3 times each day, days 2-4, day 5 given once)	Drug: Placebo Aprepitant Placebo Aprepitant 0 mg once daily for 5 days Drug: Active Aprepitant Active Aprepitant 160 mg once daily for 5 days
Experimental: Behavioral Condition 3 Placebo nicotine patch (0 mg) plus placebo oral cannabis (0 mg, 3 times each day days 2-4, day 5 given once)	Drug: Placebo Aprepitant Placebo Aprepitant 0 mg once daily for 5 days Drug: Active Aprepitant Active Aprepitant 160 mg once daily for 5 days

Arm

Intervention/Treatment

Experimental: Behavioral Condition 1

Nicotine patch (21 mg) plus placebo oral cannabis (0 mg; 3 times a day on days 2-4, given once on day 5)

Drug: Placebo Aprepitant

Placebo Aprepitant 0 mg once daily for 5 days

Drug: Active Aprepitant

Active Aprepitant 160 mg once daily for 5 days

Experimental: Behavioral Condition 2

Placebo nicotine patch (0 mg) plus oral cannabis (10 mg, 3 times each day, days 2-4, day 5 given once)

Drug: Placebo Aprepitant

Placebo Aprepitant 0 mg once daily for 5 days

Drug: Active Aprepitant

Active Aprepitant 160 mg once daily for 5 days

Experimental: Behavioral Condition 3

Placebo nicotine patch (0 mg) plus placebo oral cannabis (0 mg, 3 times each day days 2-4, day 5 given once)

Drug: Placebo Aprepitant

Placebo Aprepitant 0 mg once daily for 5 days

Drug: Active Aprepitant

Active Aprepitant 160 mg once daily for 5 days

Outcome Measures

Primary Outcome Measures

withdrawal symptom severity, measured on a 0 (not at all) to 3 (severe) scale [collected on each study day]
Subjective experience of withdrawal symptoms for cannabis, tobacco, and both (eg: Irritability, Sleep difficulty, Chills, Nervousness)
"craving" measured using the Marijuana craving questionaire and the tobacco craving questionaire [collected on each study day]
Subjective measures of craving for cannabis, tobacco, and both Questionaires are anchored with strongly disagree to strongly agree (1-7)
reinforcing effects, as measured using the Multiple Choice Questionaire [collected each day of study]
Reinforcement value of cannabis and tobacco as measured by preference for money over the administration of either drug; questionaire has 70 questions and money value vs. drug ranges from 25 cents to 25 dollars 1-70.

Secondary Outcome Measures

sleep quality [collected on each study day]
A VAS sleep questionnaire will be used each morning to assess daily sleep quality.
Neurocognitive Function [collected on days 1-4 of the study]
The purpose of examining the neurocognitive function of our participants on days 1-4 is to examine the safety of the co-administration of aprepitant at 160 mg/day with oral THC (dronabinol 10 mg) on brain function. Tasks used are the DSST - The Digit Symbol Substitution Test measures the learning of integrating visual and motor skills, and the SRTT- The Simple reaction Time Task is a well validated computerized test for assessing the effects of psychoactive drugs on performance.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability [each day of study]
Blood pressure, pulse, and a Systematic Assessment For Treatment Emergent Events (SAFTEE) are collected daily. Electrocardiograms (EKGs) are collected at baseline and discharge.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Must meet DSM-IV/ICD-10 criteria for cannabis abuse or dependence
Must be non-treatment seeking individuals
Participant does not meet DSM-IV criteria for any current (i.e., criteria met at any point in the past 30 days) dependence on a substance other than alcohol, nicotine, caffeine, or marijuana or physiological dependence on alcohol requiring medical detoxification.
No subjects who have trouble reading the English language or visual or hearing problems that may interfere with the collection of data
Not currently taking other medications (with the exception of oral contraceptives) that would preclude safe participation in this study
Must test negative for pregnancy prior to inclusion
females using birth control pills must agree to use a condom during intercourse for 1 month after participation in study because the study medication will decrease the effectiveness of the birth control pill rendering it ineffective
Should be in general good health
No evidence of recent use of other illicit drugs on a urine toxicity screen prior to admission

Exclusion Criteria:

Major current (within last 90 days) Axis I psychopathology (e.g., major depressive disorder, bipolar disorder, schizophrenia)
Presence of significant medical illness (e.g., diabetes, cardiovascular disease, hypertension, cancer, epilepsy, kidney disease)
Current, repeated illicit drug use (other than marijuana)
Subject is breastfeeding or pregnant
Concurrent therapy with drugs known to inhibit CYP3A4 activity
Request for drug treatment
Current parole or probation
Recent history of significant violent or suicide behavior
Allergic to sesame oil

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Pharmacological Research Unit (CPRU), University of Virginia School of Medicine	Charlottesville	Virginia	United States	22903
2	University of Virginia Center for Addiction Education and Treatment (UVA CARE)	Charlottesville	Virginia	United States	22908