Treatment for Cannabis Withdrawal and Dependence
Condition: Cannabis Dependence
MeSH terms: Marijuana Abuse
Intervention: Aprepitant; Placebo; Manual-guided behavioral counseling
Intervention description: 125mg/day for 8 weeks; 125mg/d placebo pill for 8 weeks; Standardized manual-guided behavioral counseling performed 1 time per week for 8 weeks in conjunction with study drug or placebo.
Intervention MeSH terms: Aprepitant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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.
    

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.