THC withdrawal in mice disrupts dopamine, sleep, and behavior, especially in males
Mice undergoing spontaneous THC withdrawal showed altered striatal dopamine release, sleep disturbances matching human withdrawal patterns, and behavioral changes, with effects more consistently observed in males.
Quick Facts
What This Study Found
THC withdrawal produced altered striatal dopamine release, sleep disturbances that mimic clinical observations (disrupted sleep architecture), and affect-related behavioral changes. These effects were more consistently observed in male mice than in females, suggesting sex-specific vulnerability to withdrawal.
Key Numbers
Dopamine release measured in multiple striatal subregions during early and late abstinence. Sleep architecture assessed before, during, and after THC treatment. Behavioral measures modeled human withdrawal symptoms.
How They Did This
Mice received a THC treatment regimen known to produce tolerance. During early and late abstinence, researchers measured electrically evoked dopamine release in brain slices, long-term polysomnographic sleep recordings, and withdrawal-related behaviors.
Why This Research Matters
Sleep disturbances are a primary driver of cannabis relapse in humans. This mouse model replicates key features of human THC withdrawal and provides a platform for studying the neural mechanisms involved.
The Bigger Picture
The sex differences in withdrawal severity align with emerging human data suggesting men and women experience cannabis withdrawal differently, which has implications for personalized treatment approaches.
What This Study Doesn't Tell Us
Mouse model may not fully replicate human withdrawal. Spontaneous withdrawal paradigm better mimics human cessation but produces subtler effects than precipitated withdrawal. Sex differences in mice may not translate directly to humans.
Questions This Raises
- ?What drives the sex difference in withdrawal severity?
- ?Could targeting striatal dopamine specifically help manage withdrawal-related sleep disturbances?
Trust & Context
- Key Stat:
- Withdrawal effects more consistent in males than females
- Evidence Grade:
- Well-designed animal study with multiple objective measures (dopamine, sleep, behavior), but mouse model has inherent limitations.
- Study Age:
- Published in 2022.
- Original Title:
- Changes in striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence in male and female mice.
- Published In:
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47(8), 1537-1549 (2022)
- Authors:
- Kesner, Andrew J, Mateo, Yolanda, Abrahao, Karina P, Ramos-Maciel, Stephanie, Pava, Matthew J, Gracias, Alexa L, Paulsen, Riley T, Carlson, Hartley B, Lovinger, David M
- Database ID:
- RTHC-03952
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Does THC withdrawal affect sleep?
Yes. In this mouse study, THC withdrawal disrupted sleep architecture in patterns that mirror clinical observations in humans, where sleep disturbance is one of the most common withdrawal symptoms.
Do males and females experience THC withdrawal differently?
In mice, withdrawal-related changes in dopamine, sleep, and behavior were more consistently observed in males, suggesting sex-specific differences in withdrawal vulnerability.
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Cite This Study
https://rethinkthc.com/research/RTHC-03952APA
Kesner, Andrew J; Mateo, Yolanda; Abrahao, Karina P; Ramos-Maciel, Stephanie; Pava, Matthew J; Gracias, Alexa L; Paulsen, Riley T; Carlson, Hartley B; Lovinger, David M. (2022). Changes in striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence in male and female mice.. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47(8), 1537-1549. https://doi.org/10.1038/s41386-022-01326-0
MLA
Kesner, Andrew J, et al. "Changes in striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence in male and female mice.." Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2022. https://doi.org/10.1038/s41386-022-01326-0
RethinkTHC
RethinkTHC Research Database. "Changes in striatal dopamine release, sleep, and behavior du..." RTHC-03952. Retrieved from https://rethinkthc.com/research/kesner-2022-changes-in-striatal-dopamine
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.