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Treatment for Cannabis Withdrawal and Dependence

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by The Scripps Research Institute
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Barbara J. Mason, The Scripps Research Institute
ClinicalTrials.gov Identifier:
NCT01611948
First received: June 3, 2011
Last updated: April 12, 2016
Last verified: April 2016
  Purpose
Cannabis is the most widely used illicit drug in the United States, and worldwide, with 1 in 10 users estimated to meet diagnostic criteria for cannabis dependence. Avoidance of withdrawal symptoms (e.g., disturbances in mood, sleep, and craving) is a common relapse precipitant. Cannabis use also impairs executive cognitive functions thereby increasing vulnerability to relapse and reducing the ability to benefit from behavioral therapy. There are no pharmacological treatments for cannabis dependence, despite the large number of afflicted individuals and the limitations of behavioral therapies which do not remediate withdrawal and are associated with high rates of treatment failure. The primary aim of this clinical trial is to evaluate the efficacy and safety of a novel neurokinin1 (NK1) receptor antagonist, aprepitant (Emend), (125mg/day), in outpatients with current cannabis dependence. The main hypothesis to be tested is to evaluate the relative efficacy of aprepitant 125 mg/d vs. placebo for reducing cannabis withdrawal symptoms in cannabis dependent outpatients, specifically anxiety, mood, craving and sleep.

Condition Intervention Phase
Cannabis Dependence
Drug: Aprepitant
Drug: Placebo
Behavioral: Manual-guided behavioral counseling
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pharmacological Treatment of Cannabis Withdrawal and Dependence

Resource links provided by NLM:


Further study details as provided by The Scripps Research Institute:

Primary Outcome Measures:
  • Change in Cannabis Use from Baseline to 12 weeks [ Time Frame: Once per week for 12 weeks ] [ Designated as safety issue: No ]
    Urinary THC


Estimated Enrollment: 100
Study Start Date: May 2011
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active Drug
125mg/d aprepitant for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.
Drug: Aprepitant
125mg/day for 8 weeks
Other Name: Emend
Behavioral: Manual-guided behavioral counseling
Standardized manual-guided behavioral counseling performed 1 time per week for 8 weeks in conjunction with study drug or placebo.
Other Name: Manual-guided therapy
Placebo Comparator: Placebo pill
Placebo pill daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.
Drug: Placebo
125mg/d placebo pill for 8 weeks
Behavioral: Manual-guided behavioral counseling
Standardized manual-guided behavioral counseling performed 1 time per week for 8 weeks in conjunction with study drug or placebo.
Other Name: Manual-guided therapy

Detailed Description:

This study will be a Phase II, single-site, 8-week, randomized, double-blind, placebo-controlled, parallel group comparison of aprepitant (125 mg/d) or placebo. Subjects will be 100 outpatients seeking treatment for current cannabis dependence with no clinically significant medical or psychiatric disorders (including substance use disorders or a positive drug screen for substances other than cannabis or nicotine). All subjects will receive weekly manual-guided abstinence-oriented counseling to facilitate showing a drug effect above and beyond available therapies (Weeks 0-8). Research assessments of marijuana use and withdrawal and drug safety and tolerability will occur weekly through the treatment phase of the 8-week study. Post treatment follow-up assessments will occur at Weeks 9 and 12. Neuropsychological testing will occur at Weeks 0 and 4 and 8.

Specific Aim 1: To evaluate the relative efficacy of aprepitant 125 mg/d vs. placebo for reducing cannabis withdrawal symptoms in cannabis dependent outpatients, including anxiety, mood, craving and sleep symptoms.

Specific Aim 2: To evaluate the relative efficacy of aprepitant 125 mg/d vs. placebo for reducing marijuana use in cannabis dependent outpatients.

Specific Aim 3: To evaluate the relative efficacy of aprepitant 125 mg/d vs. placebo for reducing cannabis related impairments in executive functioning in cannabis dependent outpatients.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females from 18-70 years of age
  • Meets DSM IV criteria for current cannabis dependence
  • Seeking research-based outpatient treatment for cannabis dependence that involves daily oral medication
  • Smoked MJ daily at least 25 days per month during the 90 days prior to randomization
  • Current cannabis use verified by a positive urine test > 50 ng/ml
  • At least a 2-year history of regular MJ use
  • Willing and able to give informed consent

Exclusion Criteria:

  • Abstinent from cannabis more than 2 days at the time of randomization
  • Currently meets DSM IV criteria for dependence on substances, or has urine drug screen positive for substances, other than cannabis or nicotine
  • Meets DSM IV criteria for a major AXIS I disorder other than cannabis and nicotine dependence,
  • Active suicidal ideation
  • Significant medical disorders that will increase potential risk or interfere with study participation,
  • Females who are pregnant, nursing or who are sexually active with child-bearing potential and refuse to use a double-barrier method of birth control during the study and for up to 4 weeks after study termination
  • Ongoing treatment with medications that may affect study outcomes,
  • Use of CYP3A4 strong inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) and CYP3A4 moderate inhibitors (e.g., diltiazem) within the 2 week period prior the study drug administration or within 5 half-lives of the respective medication, whichever is longer, until study conclusion.
  • Consumption of grapefruit or grapefruit products from at least 2 weeks prior to study drug administration until study conclusion.
  • Ongoing treatment with medications that are primarily metabolized by CYP3A4 and may have increased plasma concentrations when co-administered with aprepitant, such as pimozide, terfenadine, astemizole or cisapride or corticosteroids, as well as benzodiazepines including midazolam, alprazolam, and triazolam.
  • Ongoing treatment with medications that are primarily metabolized by CYP2C9 (e.g., warfarin, tolbutamide).
  • Use of drugs (e.g., rifampin, carbamazepine, phenytoin) or herbal supplements (e.g., St John's wort) that induce CYP3A4 activity and may result in reduced plasma concentrations of aprepitant and decreased efficacy of aprepitant.
  • Inability to understand and/or comply with the provisions of the protocol and consent form.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01611948

Contacts
Contact: Nicholas J Chesher, Ph.D. 858-784-7465 nchesher@scripps.edu

Locations
United States, California
The Scripps Research Institute Recruiting
La Jolla, California, United States, 92037
Contact: Nicholas J. Chesher, Ph.D.    858-784-7465    nchesher@scripps.edu   
Principal Investigator: Barbara J Mason, Ph.D.         
Sponsors and Collaborators
The Scripps Research Institute
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Barbara J Mason, Ph.D. The Scripps Research Institute
  More Information

Additional Information:
Responsible Party: Barbara J. Mason, Principal Investigator, The Scripps Research Institute
ClinicalTrials.gov Identifier: NCT01611948     History of Changes
Other Study ID Numbers: DA030988  5R01DA030988-05 
Study First Received: June 3, 2011
Last Updated: April 12, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Marijuana Abuse
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Aprepitant
Fosaprepitant
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 26, 2016