A Role for Cannabinoid CB2 Receptor in Tourette Syndrome: MRI Brain Imaging

Grant Type
Basic
Grant Year
2012-2013
Institution Location
Foreign
Institution Organization Name
Ariel University Center Israel
Investigators Name
Anavi-Goffer, Sharon, PhD

Tourette Syndrome is defined as part of a spectrum of tic disorders. It is a neuropsychiatric disorder of unknown etiology, with onset in childhood and is characterized by multiple involuntary motor tics and at least one vocal tic. In 90% of Tourette Syndrome children, the tics exist in conjunction with another disorder, most frequently co-occurring with Attention-Deficit Hyperactivity Disorder (ADHD). Therapeutic effects of the plant Cannabis Sativa in patients with either or both Tourette Syndrome and ADHD suggest the core involvement of the endogenous cannabinoid system in these disorders. The “endocannabinoid” ligands, their receptors and degradative enzymes constitute the major parts of the “endocannabinoid system”. This proposal is focused on the role of CB2 receptor, a member of the G-protein coupled receptor superfamily and of the endogenous cannabinoid system, in the development of motor tic disorders. Our data show that postnatal administration of selective CB2 receptor ligands induces both ADHD-like symptoms and vocal/motor tics, lasting into adulthood. In contrast, our results show that Rimonabant (SR141716A), a CB1 receptor antagonist, induces only ADHD-like behavior in line with a study in Tourette Syndrome patients that did not reveal a link with mutations in the cannabinoid CB1 receptor gene. Evidence exists for functional CB2 receptors on microglia and neurons in different brain regions and for up-regulation of CB2 receptor expression level in the brain during CNS pathologies. However, the functional signaling of CB2 receptor in Tourette Syndrome is still to be characterized. Our results suggest that postnatal modulation of individual cannabinoid receptors selectively contributes to the development of distinct neuropsychiatric profiles. The goal of this study is to investigate of the effect of drug candidates on TS/ADHD symptoms and to compare with MRI the selective changes that are induced in the brain structure. Sharon Anavi-Goffer, Ph.D. Ariel University Center, Ariel, Israel Award: $60,000 (2nd Year Funding) Tourette Association of America Inc.. – Research Grant Award 2012-2013