First-break psychosis and mycoplasma-associated encephalitis: a case series highlighting the role of cannabis use, immune-based interventions, and antipsychotic treatment

First-episode psychosis (FEP) in adolescents poses challenges when distinguishing between primary psychiatric disorders and organic causes like autoimmune encephalitis. Mycoplasma pneumoniae can lead to neuropsychiatric symptoms, including psychosis. However, its connection to first-break psychosis has not been fully studied. The diagnostic challenge grows with the use of substances, especially cannabis. In this study, we discuss two adolescent cases of first-break psychosis associated with Mycoplasma and cannabis use. In Case 1, a 15-year-old girl experienced treatment-resistant psychosis, with multiple antipsychotic medications failing to help. An evaluation showed cerebrospinal fluid (CSF) pleocytosis and high Mycoplasma IgM/IgG antibodies. She showed significant improvement 48 hours after completing doxycycline. In Case 2, a 17-year-old boy displayed disorganized thoughts, hallucinations, and dystonic movements. Laboratory tests revealed CSF pleocytosis and positive Mycoplasma serology. He responded well to intravenous immunoglobulin and azithromycin, returning to his usual level of functioning. Both patients had used cannabis and were initially diagnosed with substance-induced psychosis before the organic causes were found. These cases emphasize the need to consider infectious and autoimmune factors in adolescents with sudden, treatment-resistant psychosis, even when there is a history of substance use. Their positive response to antimicrobial and immunomodulatory treatment suggests that early recognition and treatment of Mycoplasma-associated encephalitis may lead to better outcomes and help avoid long-term psychiatric issues.