Novel potential avenues for the therapy of Tourette syndrome: Cannabinoid- and steroid-based interventions

Abstract

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and vocal tics. Current pharmacological treatments are inconsistently effective and often associated with significant adverse events, underscoring the need for better alternative therapeutic options. Here, we discuss the available evidence on the therapeutic potential of cannabinoid- and steroid-related drugs, two families of compounds showing promise as alternatives to standard treatments. The first robust evidence of the therapeutic potential of cannabinoids came from patient surveys pointing to marijuana's beneficial effects on tic severity. Based on this evidence, the therapeutic effects of the main psychoactive cannabis ingredient, Δ9-tetrahydrocannabinol (THC), were studied in two small randomized clinical trials. The results of these investigations indicate that that THC may only have modest efficacy in reducing tic severity. However, recent preliminary evidence suggests that combining THC with other cannabinoids or related compounds may elicit therapeutic effects in TS patients. At the same time, the use of cannabinoids in TS remains highly controversial, given the significant risk of psychopathology associated with these drugs, particularly in children and adolescents. Growing evidence also points to a central role of neuroactive steroids in TS pathophysiology, yet clinical investigations on steroid-related drugs as therapies for tic disorders remain only preliminary. Steroidogenesis inhibitors, such as finasteride, may show some promise for treating adult male TS patients; however, more extensive randomized, double-blind clinical trials are warranted to ascertain the therapeutic value of these medications. In conclusion, while cannabinoids and steroids may afford new avenues for treating tic disorders, evidence on these drugs remains rudimentary, and more extensive research is warranted to define their therapeutic potential as well as their toxicity.