Treatment for Cannabis Withdrawal and Dependence

March 29, 2017 updated by: Barbara J. Mason, The Scripps Research Institute

Pharmacological Treatment of Cannabis Withdrawal and Dependence

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92037
        • The Scripps Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Active Drug
125mg/d aprepitant for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.
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 Names:
  • Manual-guided therapy
Drug: Aprepitant
125mg/day for 8 weeks
Other Names:
  • Emend
PLACEBO_COMPARATOR: Placebo pill
Placebo pill daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.
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 Names:
  • Manual-guided therapy
Drug: Placebo
125mg/d placebo pill for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Week 0 in Cannabis Use Using Urinary CN-THCCOOH Levels at Week 8
Time Frame: Week 0 and Week 8
Urinary THC/Cr ratio, also known as CN-THCCOOH (creatinine normalized tetrahydrocannabinol carboxylic acid), is a highly sensitive and specific quantitative analytic procedure to determine current marijuana metabolite levels in the urine as well as new marijuana use or abstinence. Gas chromatography mass spectrometric levels of 11-nor-9-carboxy-9-THC (THC-COOH), the primary marijuana metabolite, are normalized to the urine creatinine (CN) concentration to reduce the variability of drug measurement attributable to urine dilution. Negative values indicate decreased use. Change = (Week 8 value - Week 0 value).
Week 0 and Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Scripps Research Institute

Collaborators

National Institute on Drug Abuse (NIDA)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (ACTUAL)

October 1, 2015

Study Completion (ACTUAL)

October 1, 2015

Study Registration Dates

First Submitted

June 3, 2011

First Submitted That Met QC Criteria

June 4, 2012

First Posted (ESTIMATE)

June 5, 2012

Study Record Updates

Last Update Posted (ACTUAL)

May 1, 2017

Last Update Submitted That Met QC Criteria

March 29, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DA030988
  • 5R01DA030988-05 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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