Medicinal Cannabis Plant Extract (NTI164) modifies epigenetic, ribosomal, and immune pathways in paediatric acute-onset neuropsychiatric syndrome

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%). Clinical assessments demonstrated significant improvements with NTI164 in disease severity, emotional regulation, anxiety, OCD, ADHD symptoms, and overall quality of life (all p<0.05). Cytokine and multi-omics analyses, including transcriptomics, proteomics, phosphoproteomics, and DNA methylation, revealed baseline dysregulation in epigenetic (chromatin remodelling, methylation, histone modifications, transcription factors), ribosomal, immune, and signalling pathways in PANS versus controls. These abnormalities were significantly modified following NTI164 treatment. These results suggest NTI164 has broad epigenetic and immune modulatory effects, modifying baseline immune cell abnormalities in PANS. While further controlled studies are warranted, NTI164 shows promise as a novel therapeutic for PANS.