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 Δ⁹-tetrahydrocannabinol (Δ⁹-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

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 versus ESR = grooming > HTR in young adult versus juvenile mice. Δ⁹-THC (5 mg·kg⁻¹) induced severe adverse effects in the form of cataleptic behaviour in control mice and significantly increased ESR in juveniles. The pharmacological effects of CBD have not been studied in models of Tourette syndrome. In juveniles, CBD had no effect on DOI-induced ESR and grooming behaviours. CBD alone induced side effects, significantly increasing the frequency of HTR in juveniles and young adults.

Conclusion and Implications

Δ⁹-THC efficaciously reverses peripheral but not central motor tics. Δ⁹-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.