Quetiapine Pharmacotherapy for Cannabis Dependence (QUEST)
Despite a benign public perception, marijuana use disorders represent a significant public health problem. The development of safe and effective pharmacotherapies for marijuana dependence is an important unmet public health need. Quetiapine, an effective atypical antipsychotic that acts by blocking serotonin type 2A, dopamine type 2, histamine type 1, and adrenergic receptors, is a promising treatment for substance use disorders. In animal models, quetiapine blocks the enhancement of reward by cocaine, which is likely due to its actions on both dopamine and non-dopamine neurotransmission. Clinical studies of quetiapine have shown benefit for the treatment of alcohol and cocaine use disorders.
Conceptually, the clinically prominent effects of quetiapine, namely sedation, anxiolysis, mood stabilization and appetite stimulation, are a good match for the symptoms of marijuana withdrawal. Most importantly, an open-label dose-finding study of quetiapine for the treatment of marijuana dependence conducted by our research group determined that quetiapine was well-tolerated and associated with reductions in marijuana use indicating that it is a promising agent deserving of further study in marijuana-dependent outpatients.
The proposed research project is a randomized double-blind placebo-controlled clinical trial to evaluate the efficacy of quetiapine for the treatment of marijuana dependence over a 12-week period. All participants will receive Medical Management, a medication adherence focused psychosocial intervention that facilitates compliance with study medication and other study procedures, promotes abstinence from marijuana and other substances, and encourages mutual-support group attendance. All participants will receive voucher incentives for compliance with study visit attendance, returning study medication bottles, and completing other study procedures, with the objective of achieving a highly compliant sample. The goal of this phase II clinical trial is to build on our promising open-label pilot study results and examine the efficacy of quetiapine on participants' marijuana consumption under placebo-controlled double-blind conditions using an abstinence-initiation model, where participants will be using marijuana regularly at study entry, reduce their use, and then achieve abstinence. The specific aims of the projects are to determine whether quetiapine is superior to placebo in 1) reducing marijuana use and 2) achieving abstinence.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Quetiapine Pharmacotherapy for Cannabis Dependence|
- Marijuana Use [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]The daily dollar value of marijuana used averaged over a one-week period as recorded by the Timeline Followback method and confirmed by creatinine-normalized quantitative urine THC levels.
- Marijuana Abstinence [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]The number of abstinent days per week as recorded by the Timeline Followback method and confirmed by creatinine-normalized quantitative urine THC levels
- Urine toxicology [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Twice weekly urine toxicology samples negative for cannabinoids - dichotomous longitudinal
- Marijuana withdrawal symptoms [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Measured by weekly Marijuana Withdrawal Checklist (MWC) - continuous longitudinal
- Marijuana craving [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Measured by weekly Marijuana Craving Questionnaire (MCQ) - continuous longitudinal
- Sleep disturbance [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Measured by the Medical Outcomes Study—Sleep Scale (MOS-SS) - continuous longitudinal
- Retention [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Study drop out will be recorded.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||July 2017|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Other Name: Matched Placebo
Quetiapine pharmacotherapy for cannabis dependence
Other Name: Seroquel
In a 12-week randomized double-blind placebo-controlled clinical trial, we will evaluate the efficacy of quetiapine for the treatment of marijuana dependence in 150 outpatients. Participants will be randomly assigned to treatment under double-blind conditions with either a fixed dosing schedule of quetiapine or placebo. All participants will receive Medical Management, a medication adherence focused psychosocial intervention that facilitates compliance with study medication and other study procedures, and promotes abstinence from marijuana and other substances. All participants will receive progressive voucher incentives for compliance with study visit attendance and completing other study procedures, with the objective of achieving a highly compliant sample.
The results of a dose-finding pilot study of quetiapine for the treatment of marijuana dependence (see Preliminary Studies) suggests that the ideal dosing for the proposed project is a single 300 mg dose every evening, achieved after a gradual three-week titration. Clinical experience with this medication for treatment of marijuana dependence indicates that a gradual upward titration of dose is advisable to maximize tolerability and that morning dosing was poorly tolerated. Quetiapine (immediate release formulation) will be administered in 25 and 100 mg capsules; placebo capsules will appear identical to the quetiapine capsules. Participants in both treatment arms will take the same number of pills on the same schedule. Study medication will be dispensed on a weekly basis starting with the baseline visit. Quetiapine will be titrated over a three-week period to the target dose of 300 mg or the maximum tolerated dose. The research psychiatrist will make dose reductions for tolerability if necessary.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01697709
|Contact: John J Mariani, MDfirstname.lastname@example.org|
|United States, New York|
|New York State Psychiatric Institute||Recruiting|
|New York, New York, United States, 10032|
|Contact: John J Mariani, MD 212-923-3031 email@example.com|
|Principal Investigator: John J Mariani, MD|
|Principal Investigator:||John J Mariani, MD||Columbia University/NYSPI|