Effectiveness Study of Dronabinol and BRENDA for the Treatment of Cannabis Withdrawal
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|ClinicalTrials.gov Identifier: NCT00480441|
Recruitment Status : Completed
First Posted : May 31, 2007
Last Update Posted : January 18, 2012
|First Submitted Date ICMJE||May 30, 2007|
|First Posted Date ICMJE||May 31, 2007|
|Last Update Posted Date||January 18, 2012|
|Study Start Date ICMJE||August 2006|
|Actual Primary Completion Date||June 2009 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT00480441 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Structural and perfusion brain differences will be correlated with performance on neurocognitive tasks [ Time Frame: at baseline and after 2 weeks of medications ]|
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Effectiveness Study of Dronabinol and BRENDA for the Treatment of Cannabis Withdrawal|
|Official Title ICMJE||A Phase II Double-Blind Placebo-Controlled Trial of Dronabinol and BRENDA for the Treatment of Cannabis Withdrawal|
This treatment study is targeted specifically for those who want to stop using marijuana. We want to find out if patients who are dependent on marijuana and want to stop using are helped by a combination of the drug dronabinol and six sessions of individual therapy (BRENDA). Dronabinol is a pill form of the active ingredient in marijuana (THC). Currently, dronabinol is approved for the treatment of nausea in people receiving cancer chemotherapy and as an appetite stimulant in people with AIDS.
In some studies, dronabinol reduced the amount of psychological and physical discomfort experienced when people stopped using marijuana. One purpose of our study is to see if people who are on dronabinol have fewer problems with psychological and physical discomfort than those who are on a placebo.
In addition to treatment, this research trial will also be measuring the reactions of subjects to drug-related cues, and also to computer-presented tasks unrelated to drug use. We may examine whether the response to these cues/tasks either predicts treatment outcome, or is affected by your treatment. This information may also help us to understand the ways in which chronic drug use causes changes in our subjects' mental functioning and how those changes respond to treatment.
In addition to participation in the treatment research trial, some subjects may be asked to undergo a brain scan in an MRI. The purpose of the brain scan research project is to measure brain reactions with a non-invasive, non-radioactive imaging technique known as fMRI (functional magnetic resonance imaging) in marijuana subjects before and after treatment with the medication dronabinol or with an inactive substance (placebo).
1. Background: Cannabis is the most widely used illicit drug in the U.S. According to the 2004 U.S. The 2004 NSDUH estimates there are 3.2 million daily or almost daily marijuana smokers in the United States. Recent reports have estimated that 1.5% of the US population meets DSM-IV diagnostic criteria for cannabis abuse or dependence, with the sharpest increases among young black men and women and young Hispanic men (2). Cannabis users commonly endorse adverse psychosocial and medical effects from their cannabis use, which include dysphoria, loss of control over use, cognitive impairment, and strained social relationships.
In humans, the cannabis withdrawal syndrome is a constellation of affective and behavioral symptoms that occur within 24 to 48 hours after abrupt cessation of marijuana use with a gradual return to baseline after 1-2 weeks. A recent review of the literature on cannabis withdrawal identified consistent reports of anxiety, irritability, physical discomfort, insomnia, and appetite suppression to be associated with abrupt cessation of cannabis use in heavy users across controlled inpatient and outpatient trials.
The agonist dronabinol (Marinol) has shown promise in the prevention of cannabis withdrawal in human lab studies and its reported amelioration of anxiety, misery, insomnia, drug craving and appetite suppression from abrupt cannabis cessation provides the rationale for its use as an agent to prevent cannabis withdrawal in an outpatient, treatment seeking population(9). Dronabinol has also been used as a brief "maintenance" treatment in a cannabis self-administration study in humans. Currently, dronabinol is indicated for treatment of AIDS-related anorexia and nausea associated with cancer chemotherapy. Two principle aims of our proposal are therefore to gain familiarity with cannabis withdrawal in a naturalistic outpatient treatment setting and compare an agonist therapy to placebo to attenuate cannabis withdrawal and enhance treatment outcome.
The general pattern of low rates of total abstinence and lack of significant differences between high intensity psychotherapy treatment vs. low intensity and voucher-based treatment holds across all psychosocial treatment studies. In keeping with prior evidence supporting the relative efficacy of brief interventions for cannabis dependence, the current proposal will apply a well-established brief medicalized psychotherapy known as B.R.E.N.D.A. for the treatment of cannabis dependence.
To date, studies evaluating cannabis patients have primarily focused on identifying neurotoxic drug effects such as impaired learning, memory, attention and executive function. We propose to more fully examine the behaviors with relevance to addiction vulnerability and relapse. Such behaviors include but are not limited to poor inhibition, high risk-taking, positive affective bias toward drug stimuli, poor affect regulation, and poor decision-making. We plan to utilize standardized tasks and questionnaires to objectively characterize dimensions of these addiction relevant behaviors in cannabis patients and to examine the effect of cannabis withdrawal and dronabinol treatment on these behavioral measures. We will also correlate brain differences (structural and functional) with behavioral measures in cannabis dependent patients before and after treatment with dronabinol as compared to placebo.
The search for effective treatment of addictive disorders is limited by our incomplete knowledge about the brain substrates critical for addiction and for addiction recovery. The recent use of PET and fMRI has allowed researchers to examine connections between brain activity and vulnerability to addiction and relapse. In marijuana users, PET and fMRI techniques have been used to study regional brain volumes, blood flow, metabolism. However, understanding cue induced craving is more immediately relevant to treatment and relapse prevention in cannabis addiction since cannabis users have a high rate of relapse compared to those found for other drugs of abuse. In addiction, cues that have been consistently associated with drug reward can trigger craving for the drug. Clinically, the craving for the drug is sufficiently compelling in many cases to precipitate a relapse despite significant effort on the patient's part to maintain abstinence and despite significant negative consequences. Although PET and fMRI techniques have been successfully used to study cue induced craving in other drugs of abuse (e.g. cocaine) leading to greater understanding of the mechanism of relapse (limbic activation in response to drug cues), these techniques have not been utilized in cannabis patients. Several preliminary studies used patient self-report to demonstrate cue induced craving in cannabis patients. We propose to utilize physiological measures and functional neuroimaging to objectively demonstrate cue-induced craving in cannabis dependent subjects and to identify the brain substrates that mediate this craving. Similarly, dronabinol reduced self-reported drug craving in one recent human laboratory study. We propose to examine whether dronabinol will change physiological measures and brain activation in response to drug cues.
2. Study objectives:
3. Location: This is a single site study. All patient recruitment and data collection will occur at the Treatment Research Center at the University of Pennsylvania, 3900 Chestnut Street, Philadelphia, PA 19104, except for the Neuroimaging which will take place at the HUP6 fMRI in the basement of the Hospital of the University of Pennsylvania, 34th and Spruce Streets, Philadelphia, PA 19104.
4. Research design & methodology: This is a Phase 2 double blind placebo controlled trial. We will recruit 60 cannabis dependent subjects and treat them with the combination of dronabinol 10mg QID (four times per day) and BRENDA or placebo qid (four times per day) and BRENDA to reduce their consumption of cannabis. Subjects will be 60 men and women with current DSM-IV diagnosis of cannabis dependence. All patients will receive six sessions of BRENDA at visits 1, 3, 6, 9, 11, and 12. The study length for each patient will be one week for screening and baseline self-report and neurocognitive battery measures. Patients who qualify will be offered an opportunity to participate in the fMRI portion of the study with baseline fMRI obtained in the first week prior to starting medications and second fMRI obtained during week two of medications. This is followed by 3 weeks of medication and, after completing medications, three additional weekly visits (two for BRENDA and one for final assessment).
5. Duration: Each subject will participate in a 7 week treatment trial with the following schedule of visits: STUDY VISITS
Week 1 (Baseline Measures):
Week 2 - 4 (Medication Treatment):
Weeks 5-6 (Medication Washout)
Week 7 (Final Visit):
We anticipate that we will require two years to complete data collection with 60 subjects and will require one year for data analysis. Thus, the proposed study will be completed in approximately three years.
SUBJECT SELECTION & WITHDRAWAL
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Condition ICMJE||Marijuana Dependence|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date||July 2009|
|Actual Primary Completion Date||June 2009 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Additional Neuroimaging Exclusion Criteria:
Subjects who are selected for the clinical trial based on above inclusion and exclusion criteria will be screened further with the following exclusion criteria for possible participation in the fMRI imaging session:
|Ages||18 Years to 55 Years (Adult)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00480441|
|Other Study ID Numbers ICMJE||5P60DA005186-19( U.S. NIH Grant/Contract )
5P60DA005186-19 ( U.S. NIH Grant/Contract )
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Marina Goldman, M.D., University of Pennsylvania|
|Study Sponsor ICMJE||University of Pennsylvania|
|Collaborators ICMJE||National Institute on Drug Abuse (NIDA)|
|PRS Account||University of Pennsylvania|
|Verification Date||January 2012|
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