Cannabis-derived treatments target gut-brain connection

Autism spectrum disorder (ASD; autism) is a prevalent and heterogeneous neurodevelopmental disorder characterised by social communication difficulties, repetitive behaviour, and restricted interests. For individuals with autism, in particular those who require substantial care-giver support, irritability, heightened sensitivity and aggressive behaviours in response to sensory, social, or environmental triggers can limit access to health, education and community services and impact quality of life. Although gastrointestinal (GI) symptom severity is associated with irritable behaviours in autism, there are few approved medications to address challenging behaviour or comorbid psychiatric disorders, or gut dysfunction in autism. Here, we review the mode of action of drugs undergoing clinical trials for treating irritable behaviour and improving social communication as well as potentially gastrointestinal symptoms in individuals with autism. Repurposed medications such as pimavanserin (an atypical antipsychotic) and the antiparasitic suramin are being trialled for treating irritable behaviours and impaired social interaction, respectively, in autism. NTI164 is a medicinal cannabis-derived biopharmaceutical undergoing clinical safety and efficacy trials for improving social communication and similarly, ML-004 is an investigational drug being assessed for treating social communication deficits. Two other repurposed medications previously utilised for schizophrenia; brexpiprazole and lumateperone, as well as AB-2004, a microbial metabolite sequestering agent (with proposed actions on gut function), are undergoing clinical trials to assess impacts on irritability associated with autism. We also outline emerging findings from clinical studies on the use of gut-targeted small molecules and bacteriophage therapy, prebiotics, probiotic supplementation and faecal microbiota transplantation (FMT), and their potential impact on behavioural symptoms in autism.