NCT01697709: QUEST

Quetiapine Pharmacotherapy for Cannabis Dependence

Completed Phase 2 Results posted Last updated 5 March 2019

What this trial tests

Phase 2 trial testing Quetiapine in Cannabis Dependence in 130 participants. Completed in 30 April 2017.

Timeline

1 October 2012

Primary endpoint
30 April 2017

30 April 2017

Quick facts

Lead sponsor	New York State Psychiatric Institute
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	130
Start date	1 October 2012
Primary completion	30 April 2017
Estimated completion	30 April 2017
Sites	1 location across United States

Drugs / interventions tested

• Quetiapine (quetiapine) — full drug profile →
• Placebo

Conditions studied

• Cannabis Dependence — all drugs for Cannabis Dependence →

Sponsor

New York State Psychiatric Institute

Who can join

Adults 18 to 60, any sex, with Cannabis Dependence. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Marijuana Use, Daily Dollar Averaged Over 7 Days During Each of 12 Weeks of Study Primary · 12 weeks or length of participants involvement

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

week 1

Group	Value	95% CI
Placebo	14.00	5.42 – 21.25
Quetiapine	7.00	3.18 – 12.86

week 2

Group	Value	95% CI
Placebo	10.00	2.86 – 22.00
Quetiapine	8.00	3.02 – 12.70

week 3

Group	Value	95% CI
Placebo	7.14	2.64 – 17.69
Quetiapine	5.86	3.29 – 11.61

week 4

Group	Value	95% CI
Placebo	6.43	1.61 – 16.25
Quetiapine	5.71	2.57 – 12.00

week 5

Group	Value	95% CI
Placebo	6.43	1.07 – 17.86
Quetiapine	4.29	1.43 – 9.29

week 6

Group	Value	95% CI
Placebo	5.71	0.96 – 13.82
Quetiapine	4.11	1.32 – 9.79

week 7

Group	Value	95% CI
Placebo	3.70	1.03 – 12.59
Quetiapine	3.57	1.43 – 7.52

week 8

Group	Value	95% CI
Placebo	2.86	1.12 – 12.26
Quetiapine	3.43	1.18 – 6.00

Number of Participants Stratified by Marijuana Abstinence Days Per Week Primary · 12 weeks or length of participation

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.

Week 1

Group	Value	95% CI
Placebo	5
Quetiapine	4
Placebo	9
Quetiapine	9
Placebo	40
Quetiapine	46

Week 2

Group	Value	95% CI
Placebo	8
Quetiapine	4
Placebo	7
Quetiapine	7
Placebo	34
Quetiapine	44

Week 3

Group	Value	95% CI
Placebo	9
Quetiapine	5
Placebo	5
Quetiapine	14
Placebo	28
Quetiapine	33

Week 4

Group	Value	95% CI
Placebo	8
Quetiapine	8
Placebo	9
Quetiapine	15
Placebo	23
Quetiapine	26

Week 5

Group	Value	95% CI
Placebo	10
Quetiapine	10
Placebo	7
Quetiapine	16
Placebo	22
Quetiapine	21

Week 6

Group	Value	95% CI
Placebo	13
Quetiapine	10
Placebo	4
Quetiapine	13
Placebo	22
Quetiapine	23

Week 7

Group	Value	95% CI
Placebo	12
Quetiapine	11
Placebo	9
Quetiapine	15
Placebo	17
Quetiapine	17

Week 8

Group	Value	95% CI
Placebo	12
Quetiapine	10
Placebo	9
Quetiapine	16
Placebo	17
Quetiapine	17

Adverse events — posted to ClinicalTrials.gov

Time frame: over 12 weeks of study or length of participation. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 0/64 (0%)

Deaths: 0/64

Quetiapine

Serious: 0/66 (0%)

Deaths: 0/66

Other adverse events (4 terms — click to expand)

Reaction	System	Placebo	Quetiapine
Hypertension	Cardiac disorders	—	—
Hyperglycemia	General disorders	—	—
Dyslipidemia	Endocrine disorders	—	—
drowsiness	General disorders	—	—

Data from ClinicalTrials.gov NCT01697709 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. The Current State of Pharmacological Treatments for Cannabis Use Disorder and Withdrawal.
   Brezing CA, Levin FR. · · 2018 · cited 88× · PMID 28875989 · DOI 10.1038/npp.2017.212
2. Non-abstinent treatment outcomes for cannabis use disorder.
   Levin FR, Mariani JJ, Choi CJ, Basaraba C, et al · · 2021 · cited 10× · PMID 34087745 · DOI 10.1016/j.drugalcdep.2021.108765