Paediatric acute-onset neuropsychiatric Syndrome (PANS) is a syndrome of infection-provoked abrupt-onset obsessive-compulsive disorder (OCD) or eating restriction. This open-label trial investigated the safety and efficacy of NTI164, a cannabis-derived medicinal formulation rich in cannabinoids (minimal tetrahydrocannabinol), at 20 mg/kg/day for 12 weeks in 14 children with chronic-relapsing PANS (mean 12.1 years, females 29%). Proteomics, phosphoproteomics, and other omics approaches revealed baseline dysregulation of multiple signalling pathways in PANS versus controls that were significantly modified following NTI164 treatment.