CB2 receptors play a complex, age- and sex-dependent role in motor tics
CB2 cannabinoid receptors are needed to suppress motor tics in adult mice, but stimulating them in juvenile mice may actually generate tics, with different effects in males and females.
Quick Facts
What This Study Found
CB2 knockout mice showed higher frequencies of repetitive behaviors. In adults, CB2 activation reduced tics, but in juveniles, CB2 agonists increased tic-like behaviors. Sex differences were observed, with HU-308 increasing tics in adult females through an off-target effect. DOI (a serotonin agonist) altered expression of CB2, GPR55, and endocannabinoid enzyme genes in the prefrontal cortex.
Key Numbers
CB2 knockout mice had higher tic frequencies. HU-308 reduced adult tics but increased juvenile tics. Off-target HU-308 effects in adult females. DOI altered CB2, GPR55, FAAH, and ABHD6 expression.
How They Did This
Animal study comparing wildtype and CB2 knockout mice of different ages and sexes. Tested the CB2 agonist HU-308 on DOI-induced head twitch, ear scratch, and grooming behaviors with and without CB1 antagonism. Gene expression analysis in prefrontal cortex.
Why This Research Matters
THC helps some Tourette syndrome patients, but understanding which cannabinoid receptors are involved, and how age and sex matter, could lead to more targeted treatments.
The Bigger Picture
The age-dependent reversal (CB2 agonists reduce tics in adults but increase them in juveniles) is particularly relevant because Tourette syndrome primarily affects children and is more common in boys.
What This Study Doesn't Tell Us
Mouse model of tics using DOI does not fully replicate human Tourette syndrome. HU-308 has off-target effects complicating interpretation. Only one dose tested for most experiments.
Questions This Raises
- ?Would age-appropriate CB2 modulation improve Tourette treatment?
- ?Could the sex difference in CB2 effects explain why TS is more common in boys?
Trust & Context
- Key Stat:
- CB2 agonists reduced adult tics but increased juvenile tics
- Evidence Grade:
- Novel animal study with multiple experimental approaches, but mouse DOI model has limited translational validity for human Tourette syndrome.
- Study Age:
- Published in 2022.
- Original Title:
- Motor-like Tics are Mediated by CB2 Cannabinoid Receptor-dependent and Independent Mechanisms Associated with Age and Sex.
- Published In:
- Molecular neurobiology, 59(8), 5070-5083 (2022)
- Authors:
- Gorberg, Victoria(3), Borisov, Veronika, Greig, Iain R(2), Pertwee, Roger G, McCaffery, Peter, Anavi-Goffer, Sharon
- Database ID:
- RTHC-03883
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Could cannabinoids help Tourette syndrome?
THC helps some patients, and this study shows CB2 receptors are important for tic suppression in adults. However, CB2 stimulation increased tics in juvenile mice, suggesting age-appropriate treatment is critical.
Why does age matter?
CB2 receptor effects reversed between juveniles and adults. Since Tourette syndrome primarily affects children, treatments effective in adults may not work or could worsen symptoms in young patients.
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Cite This Study
https://rethinkthc.com/research/RTHC-03883APA
Gorberg, Victoria; Borisov, Veronika; Greig, Iain R; Pertwee, Roger G; McCaffery, Peter; Anavi-Goffer, Sharon. (2022). Motor-like Tics are Mediated by CB2 Cannabinoid Receptor-dependent and Independent Mechanisms Associated with Age and Sex.. Molecular neurobiology, 59(8), 5070-5083. https://doi.org/10.1007/s12035-022-02884-6
MLA
Gorberg, Victoria, et al. "Motor-like Tics are Mediated by CB2 Cannabinoid Receptor-dependent and Independent Mechanisms Associated with Age and Sex.." Molecular neurobiology, 2022. https://doi.org/10.1007/s12035-022-02884-6
RethinkTHC
RethinkTHC Research Database. "Motor-like Tics are Mediated by CB2 Cannabinoid Receptor-dep..." RTHC-03883. Retrieved from https://rethinkthc.com/research/gorberg-2022-motorlike-tics-are-mediated
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.