Treatment for Cannabis Withdrawal and Dependence

NCT ID: NCT01611948

Last Updated: 2017-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2015-10-31

Brief Summary

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.

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.

Conditions

Cannabis Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active Drug

125mg/d aprepitant for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.

Group Type: ACTIVE_COMPARATOR

Aprepitant

Intervention Type: DRUG

125mg/day for 8 weeks

Manual-guided behavioral counseling

Intervention Type: BEHAVIORAL

Standardized manual-guided behavioral counseling performed 1 time per week for 8 weeks in conjunction with study drug or placebo.

Placebo pill

Placebo pill daily for 8 weeks given in conjunction with 8 weeks of manual-guided behavioral counseling.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

125mg/d placebo pill for 8 weeks

Manual-guided behavioral counseling

Intervention Type: BEHAVIORAL

Standardized manual-guided behavioral counseling performed 1 time per week for 8 weeks in conjunction with study drug or placebo.

Interventions

Aprepitant

125mg/day for 8 weeks

Intervention Type: DRUG

Placebo

125mg/d placebo pill for 8 weeks

Intervention Type: DRUG

Manual-guided behavioral counseling

Standardized manual-guided behavioral counseling performed 1 time per week for 8 weeks in conjunction with study drug or placebo.

Intervention Type: BEHAVIORAL

Other Intervention Names

Emend; Manual-guided therapy

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

The Scripps Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Barbara J. Mason

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Barbara J Mason, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The Scripps Research Institute

Locations

The Scripps Research Institute

La Jolla, California, United States

Countries

United States

Related Links

http://alcoholismmarijuanatreatment.com

Study-related information

Other Identifiers

5R01DA030988-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DA030988

Identifier Type: -

Identifier Source: org_study_id