Medications Development for the Treatment of Cannabis Related Disorders

Nicotine Dependence Clinical Trial

— MTC  

Official title:

Medications Development for the Treatment of Cannabis Related Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01204723
• Other study ID #: 14392
• Secondary ID: R01DA027131
• Status: Completed
• Phase: Phase 1
• First received: September 14, 2010
• Last updated: May 31, 2012
• Start date: August 2009
• Est. completion date: April 2012

Study information

• Verified date: May 2012
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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study in which subjects (N=72) will be randomized in a 3 x 2 factorial design to one of 3 behavioral conditions; a) withdrawn from both substances, b) withdrawn from tobacco only, or c) withdrawn from cannabis only, and to receive one of 2 medication dose conditions: placebo or aprepitant (160 mg/day).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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: April 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cannabis Abuse
• Cannabis Dependence
• Marijuana Abuse
• Marijuana Dependence
• Nicotine Dependence
• Nicotine Withdrawal
• Substance Withdrawal Syndrome
• Tobacco Use Disorder

Intervention

Drug:
• Placebo Aprepitant
Placebo Aprepitant 0 mg once daily for 5 days
• Active Aprepitant
Active Aprepitant 160 mg once daily for 5 days

Locations

Country	Name	City	State
United States	Clinical Pharmacological Research Unit (CPRU), University of Virginia School of Medicine	Charlottesville	Virginia
United States	University of Virginia Center for Addiction Education and Treatment (UVA CARE)	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
University of Virginia	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	withdrawal symptom severity, measured on a 0 (not at all) to 3 (severe) scale	Subjective experience of withdrawal symptoms for cannabis, tobacco, and both (eg: Irritability, Sleep difficulty, Chills, Nervousness)	collected on each study day	No
Primary	"craving" measured using the Marijuana craving questionaire and the tobacco craving questionaire	Subjective measures of craving for cannabis, tobacco, and both Questionaires are anchored with strongly disagree to strongly agree (1-7)	collected on each study day	No
Primary	reinforcing effects, as measured using the Multiple Choice Questionaire	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.	collected each day of study	No
Secondary	sleep quality	A VAS sleep questionnaire will be used each morning to assess daily sleep quality.	collected on each study day	No
Secondary	Neurocognitive Function	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.	collected on days 1-4 of the study	Yes
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Blood pressure, pulse, and a Systematic Assessment For Treatment Emergent Events (SAFTEE) are collected daily. Electrocardiograms (EKGs) are collected at baseline and discharge.	each day of study	Yes