Different responses of repetitive behaviours in juvenile and young adult mice to Δ9-tetrahydrocannabinol and cannabidiol may affect decision making for Tourette syndrome

BACKGROUND AND PURPOSE: Medicinal cannabis is in increasing use by patients with Tourette syndrome, a neuropsychiatric disorder that affects about 1% of the general population and has a childhood onset. However, the pharmacological effects of ∆9 -tetrahydrocannabinol (∆9 -THC) and cannabidiol (CBD) have not been systematically screened or compared between juvenile and young adult rodents in a model of Tourette syndrome.

EXPERIMENTAL APPROACH: In rodents, the administration of 2,5-dimethoxy-4-iodoamphetamine (DOI) increases head twitch response (HTR) and ear scratch response (ESR), and has been proposed as an animal model useful to respectively study motor tics and premonitory urges associated with tic disorders.

KEY RESULTS: Comparing the potency of Δ9 -THC to inhibit DOI-induced repetitive behaviours, the rank order was ESR > grooming > HTR vs. ESR = grooming > HTR in young adult vs. juvenile mice. ∆9 -THC (5 mg/kg) induced severe adverse effects in the form of cataleptic behaviour in control mice and significantly increased ESR in juvenile mice. To the best of our knowledge, the pharmacological effects of CBD have not been studied in models of Tourette syndrome. In juvenile mice, CBD had no effect on DOI-induced ESR and grooming behaviour. CBD alone induced side-effects, significantly increasing the frequency of HTR in juvenile and young adult mice.

CONCLUSIONS AND IMPLICATIONS: Δ9 -THC efficaciously reverses peripheral but not central motor tics. ∆9 -THC may reduce ambulatory movements and evoke premonitory urges in some paediatric patients. The small 'therapeutic window' in juveniles suggests that CBD may not effectively treat motor tics in children and may even exacerbate tics in a population of patients with Tourette syndrome.