Quetiapine Pharmacotherapy for Cannabis Dependence
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 3/7/2019 |
| Start Date: | October 1, 2012 |
| End Date: | April 30, 2017 |
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.
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.
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.
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.
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.
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New York State Psychiatric Institute The New York State Psychiatric Institute (NYSPI), established in 1895,...
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