Quetiapine Helped Cannabis Withdrawal Sleep and Appetite but Increased Craving and Relapse

The antipsychotic quetiapine improved sleep, food intake, and weight during cannabis withdrawal, but unexpectedly increased marijuana craving and self-administration during the relapse phase.

Cooper, Ziva D et al.·Addiction biology·2013·Moderate EvidenceRandomized Controlled Trial
RTHC-00663Randomized Controlled TrialModerate Evidence2013RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Randomized Controlled Trial
Evidence
Moderate Evidence
Sample
N=14

What This Study Found

In a double-blind, within-subjects study, 14 heavy cannabis smokers (averaging 10 joints/day) completed two 15-day medication phases (quetiapine 200 mg/day vs. placebo). During withdrawal (3 days without cannabis), quetiapine improved sleep quality, increased caloric intake, and reduced weight loss compared to placebo.

However, during the relapse phase (4 days with cannabis available), quetiapine increased marijuana craving and self-administration. This paradoxical pattern, helping with withdrawal symptoms but worsening relapse, led the authors to conclude quetiapine does not show promise as a cannabis dependence treatment.

Key Numbers

14 participants smoking 10 joints/day. Quetiapine 200 mg/day vs. placebo. Withdrawal phase: improved sleep quality, increased caloric intake, decreased weight loss. Relapse phase: increased craving, increased marijuana self-administration.

How They Did This

Double-blind, counterbalanced, within-subjects laboratory study. 14 volunteers (10 male, 4 female) smoking 10 marijuana cigarettes/day. Each medication phase: 15 days total, last 8 inpatient. Day 1: active marijuana. Days 2-4: inactive marijuana (withdrawal). Days 5-8: active marijuana available (relapse). Subjective, sleep, caloric, and behavioral measures collected.

Why This Research Matters

Cannabis withdrawal management is an unmet clinical need. While quetiapine's ability to address sleep, appetite, and weight loss is valuable, the increased craving and self-administration during the relapse phase represents a potentially dangerous trade-off that outweighs these benefits.

The Bigger Picture

This study illustrates why medication development for cannabis dependence is so challenging. A drug can successfully target withdrawal symptoms while paradoxically worsening relapse risk. Understanding why quetiapine increased craving could inform future drug development efforts.

What This Study Doesn't Tell Us

Very small sample (14 participants). Non-treatment-seeking volunteers may differ from people trying to quit. The inpatient laboratory setting does not replicate real-world quit conditions. Only one dose (200 mg/day) was tested. The within-subjects design means each participant experienced both conditions.

Questions This Raises

  • ?Why did quetiapine increase craving during the relapse phase?
  • ?Would lower doses avoid the pro-craving effect while maintaining withdrawal benefits?
  • ?Could quetiapine be combined with another medication that prevents the craving increase?

Trust & Context

Key Stat:
Quetiapine improved withdrawal symptoms but increased craving and relapse
Evidence Grade:
Double-blind within-subjects controlled study; moderate evidence despite small sample size.
Study Age:
Published in 2013. The search for effective cannabis dependence medications continues.
Original Title:
A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers.
Published In:
Addiction biology, 18(6), 993-1002 (2013)
Database ID:
RTHC-00663

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled TrialGold standard for testing treatments
This study
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal Study

Participants are randomly assigned to treatment or placebo groups to test cause and effect.

What do these levels mean? →

Frequently Asked Questions

Could quetiapine help with cannabis withdrawal symptoms?

It addressed some symptoms effectively: sleep improved, appetite increased, and weight loss decreased. However, it also increased marijuana craving and self-administration when cannabis was available again, making it a poor candidate for long-term dependence treatment. The withdrawal benefits are essentially offset by increased relapse risk.

Why would a medication help with withdrawal but worsen relapse?

Withdrawal management and relapse prevention involve different brain mechanisms. Quetiapine's sedating and appetite-stimulating effects address the insomnia and appetite loss of withdrawal. But its effects on dopamine and other neurotransmitter systems may enhance the rewarding properties of cannabis, increasing craving when the drug becomes available again.

Read More on RethinkTHC

Cite This Study

RTHC-00663·https://rethinkthc.com/research/RTHC-00663

APA

Cooper, Ziva D; Foltin, Richard W; Hart, Carl L; Vosburg, Suzanne K; Comer, Sandra D; Haney, Margaret. (2013). A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers.. Addiction biology, 18(6), 993-1002. https://doi.org/10.1111/j.1369-1600.2012.00461.x

MLA

Cooper, Ziva D, et al. "A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers.." Addiction biology, 2013. https://doi.org/10.1111/j.1369-1600.2012.00461.x

RethinkTHC

RethinkTHC Research Database. "A human laboratory study investigating the effects of quetia..." RTHC-00663. Retrieved from https://rethinkthc.com/research/cooper-2013-a-human-laboratory-study

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.