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 Overview

• Status: Completed
• Conditions: Cannabis Dependence
• Intervention / Treatment: Drug: Placebo; Drug: Quetiapine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Meets DSM-IV-TR criteria for current marijuana dependence
2. Reports using marijuana an average of 5 days per week over the past 28 days
3. Between the ages of 18 and 60
4. Able to provide informed consent and comply with study procedures
5. Seeking treatment for cannabis dependence

Exclusion Criteria:

1. Lifetime DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder.
2. Current DSM-IV criteria for any other psychiatric disorder that may, according to investigator's judgment, require either pharmacological or non-pharmacological intervention over the course of the study.
3. Patients prescribed psychotropic medications.
4. History of allergic reaction, intolerance, or hypersensitivity to Quetiapine.
5. Pregnancy, lactation, or failure to use adequate contraceptive methods in female patients who are currently engaging in sexual activity with men.
6. Unstable medical conditions, such as poorly controlled hypertension which might make participation hazardous.
7. Diabetes (whether controlled or not), meeting criteria for metabolic syndrome as defined by the NCEP (any 3 of the following: a. obesity [waist circumference > 40 inches], b. hyperglycemia [fasting glucose > 100 mg/dl or Rx], c. dyslipidemia [TG > 150 mg/dl or Rx], d. dyslipidemia [HDL cholesterol; 40 mg/dl (male), 50 mg/dl (female) or Rx], e. hypertension [130 mmHg systolic or > 85 mmHg diastolic or Rx]. Participants with a BMI > 35 will be excluded.
8. Current DSM-IV diagnosis of an alcohol or substance use disorder (abuse or dependence) other than marijuana or nicotine dependence.
9. Positive confirmed result on urine toxicology screen.
10. Are legally mandated to participate in a substance use disorder treatment program.
11. Increased risk for suicide.
12. QTc prolongation (screening electrocardiogram with Qtc > 450 msec for men, QTc > 470 msec for women) or history of QTc prolongation or using concomitant medications which prolong QTc interval.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo medication	Drug: Placebo; placebo capsules; Other Names: Matched Placebo
Experimental: quetiapine; Quetiapine treatment	Drug: Quetiapine; Quetiapine pharmacotherapy for cannabis dependence; Other Names: Seroquel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Marijuana Use, Daily Dollar Averaged Over 7 Days During Each of 12 Weeks of Study	The median daily dollar value of marijuana used averaged over a one-week period for each of the 12 weeks as recorded by the Timeline Followback method	12 weeks or length of participants involvement
Number of Participants Stratified by Marijuana Abstinence Days Per Week	The number of abstinent days per week over the 12 weeks of study as recorded by the Timeline Followback method. High Use group defined as 0-2 abstinent days per week, Medium Use Group as 3-5 abstinent days per week and Low Use Group as 6-7 abstinent days per week.	12 weeks or length of participation

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: John J Mariani, MD, Columbia University/NYSPI

Publications and helpful links

Helpful Links

• Study web site

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2012
• Primary Completion (Actual): April 30, 2017
• Study Completion (Actual): April 30, 2017

Study Registration Dates

• First Submitted: September 28, 2012
• First Submitted That Met QC Criteria: October 1, 2012
• First Posted (Estimate): October 2, 2012

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: pharmacotherapy; cannabis; marijuana
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Quetiapine Fumarate
• Other Study ID Numbers: 6623; 1R01DA031826 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No