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

The takeaway

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

Read this if you are interested in medications being tested for cannabis withdrawal and dependence.

Quetiapine improved withdrawal symptoms but increased craving and relapse

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Double-blind within-subjects controlled study; moderate evidence despite small sample size.

When this study was published

Published in 2013. The search for effective cannabis dependence medications continues.

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.

Questions still open

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?

Common 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 the original research

A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers.

Addiction biology, 18(6), 993-1002

View on PubMed ↗Publisher’s paper ↗

Citation

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