THC Withdrawal Caused Anxiety-Like Behavior in Mice for the First Time
Mice chronically treated with THC showed anxiety-like behavior during precipitated withdrawal on the elevated plus-maze, the first demonstration that cannabinoid withdrawal produces measurable anxiety in an animal model.
Quick Facts
What This Study Found
Male mice received THC (10 mg/kg) daily for 10 days. Four hours after the last dose, the CB1 antagonist SR141716 was administered to precipitate withdrawal, and mice were tested on the elevated plus-maze 30 minutes later.
In vehicle-treated mice, SR141716 had no significant effect on behavior.
In THC-treated mice, SR141716 produced a significant reduction in open arm exploration, a well-validated measure of anxiety-like behavior. At the highest dose (3.0 mg/kg), SR141716 significantly reduced percentage of open arm entries, percentage of open arm time, and absolute time in open arms.
Closed arm entries and total arm entries were not affected, confirming that the reduced open arm exploration reflected anxiety rather than altered motor activity.
This was the first evidence that cannabinoid withdrawal produces anxiety-like effects in mice.
Key Numbers
THC: 10 mg/kg daily x 10 days. SR141716: 0.3, 1.0, 3.0 mg/kg. At 3.0 mg/kg: significant reduction in % open arm entries, % open arm time, and absolute open arm time. No changes in closed or total arm entries (no motor effect).
How They Did This
Male ICR mice received daily THC (10 mg/kg) or vehicle for 10 days. SR141716 (0.3, 1.0, or 3.0 mg/kg) precipitated withdrawal 4 hours after the last dose. The elevated plus-maze was administered 30 minutes post-SR141716 for 5 minutes.
Why This Research Matters
Anxiety is one of the most commonly reported symptoms of cannabis withdrawal in humans. Having an animal model of withdrawal-induced anxiety allows researchers to investigate the neural mechanisms and test potential treatments.
The Bigger Picture
Human cannabis withdrawal commonly includes anxiety, irritability, and sleep disturbance. This mouse model specifically captured the anxiety component, complementing earlier models that measured hyperlocomotion and paw tremors (see RTHC-00359).
What This Study Doesn't Tell Us
Precipitated rather than spontaneous withdrawal. Single mouse strain and sex (male ICR mice). The elevated plus-maze measures a specific aspect of anxiety that may not fully represent the human experience. SR141716 doses may be clinically irrelevant.
Questions This Raises
- ?Does this anxiety resolve over time without intervention?
- ?Would anxiolytic medications reduce cannabinoid withdrawal anxiety?
- ?Do female mice show the same or different withdrawal anxiety patterns?
Trust & Context
- Key Stat:
- First demonstration of anxiety-like behavior during cannabinoid withdrawal in mice
- Evidence Grade:
- Preclinical study establishing a novel animal model. Well-controlled but limited to precipitated withdrawal in male mice of one strain.
- Study Age:
- Published in 2010. Cannabis withdrawal anxiety has since been extensively studied in both animal models and human populations.
- Original Title:
- Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze.
- Published In:
- Neuroscience letters, 475(3), 165-8 (2010)
- Authors:
- Huang, Peng(2), Liu-Chen, Lee-Yuan(2), Kirby, Lynn G
- Database ID:
- RTHC-00422
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Do humans experience anxiety during cannabis withdrawal?
Yes, anxiety is one of the most commonly reported symptoms of human cannabis withdrawal, along with irritability, sleep problems, and decreased appetite. This mouse study provided the first animal model demonstrating this symptom.
What is the elevated plus-maze?
It is a cross-shaped platform with two open (exposed) and two enclosed arms. Anxious animals spend less time in the open arms. It is a standard test for anxiety-like behavior in rodents and is used to evaluate potential anxiety treatments.
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Cite This Study
https://rethinkthc.com/research/RTHC-00422APA
Huang, Peng; Liu-Chen, Lee-Yuan; Kirby, Lynn G. (2010). Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze.. Neuroscience letters, 475(3), 165-8. https://doi.org/10.1016/j.neulet.2010.03.071
MLA
Huang, Peng, et al. "Anxiety-like effects of SR141716-precipitated delta9-tetrahydrocannabinol withdrawal in mice in the elevated plus-maze.." Neuroscience letters, 2010. https://doi.org/10.1016/j.neulet.2010.03.071
RethinkTHC
RethinkTHC Research Database. "Anxiety-like effects of SR141716-precipitated delta9-tetrahy..." RTHC-00422. Retrieved from https://rethinkthc.com/research/huang-2010-anxietylike-effects-of-sr141716precipitated
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.