Treatment for Cannabis Withdrawal and Dependence

NCT01611948 | Completed Phase 2 Results

• 2 other identifiers: DA0309885R01DA030988-05
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Cannabis Dependence

Outcome Measures

Primary Outcomes (1)

• Change From Week 0 in Cannabis Use Using Urinary CN-THCCOOH Levels at 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

Study Arms (2)

Active Drug

ACTIVE COMPARATOR

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

Drug: Aprepitant; Behavioral: Manual-guided behavioral counseling

Placebo pill

PLACEBO COMPARATOR

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

Drug: Placebo; Behavioral: Manual-guided behavioral counseling

Interventions

Aprepitant DRUG

125mg/day for 8 weeks

Also known as: Emend

Active Drug

Placebo DRUG

125mg/d placebo pill for 8 weeks

Placebo pill

Manual-guided behavioral counseling BEHAVIORAL

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

Also known as: Manual-guided therapy

Active Drug; Placebo pill

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Scripps Research Institute: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

The Scripps Research Institute

La Jolla, California, 92037, United States

Location

Related Links

• Study-related information

MeSH Terms

Conditions

Marijuana Abuse

Interventions

Aprepitant

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Barbara Mason
• Organization: The Scripps Research Institute

mason@scripps.edu

(858) 784-7324

Study Officials

• Barbara J Mason, Ph.D.

  The Scripps Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 3, 2011
• First Posted: June 5, 2012
• Study Start: May 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: May 1, 2017
• Results First Posted: March 27, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)