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.
Tourette syndrome researchers and clinicians interested in cannabinoid-based treatments.
CB2 agonists reduced adult tics but increased juvenile tics
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
What this study cannot 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.
How to read the evidence
Novel animal study with multiple experimental approaches, but mouse DOI model has limited translational validity for human Tourette syndrome.
When this study was published
Published in 2022.
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.
Questions still open
- Would age-appropriate CB2 modulation improve Tourette treatment? Could the sex difference in CB2 effects explain why TS is more common in boys?
Common questions
Could cannabinoids help Tourette syndrome?
Why does age matter?
Read the original research
Motor-like Tics are Mediated by CB2 Cannabinoid Receptor-dependent and Independent Mechanisms Associated with Age and Sex.
Molecular neurobiology, 59(8), 5070-5083
Citation
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
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