Using cortical spheroids to study endocannabinoids and autism spectrum disorder

The endocannabinoid system may play a role in the development of autism spectrum disorder and might be key to treating people with severe forms of the condition. In this commentary, Dr Karen Litwa, Assistant Professor at East Carolina University’s Brody School of Medicine, US explores how a bioelectronic assay is helping unravel the complex relationship between the endocannabinoid system and autism spectrum disorder in stem cell-derived spheroids, work that could help reveal novel therapeutic targets.

Chemicals found in cannabis are similar to naturally occurring endocannabinoids, the class of compounds that act as neurotransmitters in the body’s complex endocannabinoid system (ECS). Scientists believe this system maintains equilibrium in the brain. Imbalances in the ECS have been associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and some evidence has shown that consuming cannabis can relieve ASD symptoms. In the hope of setting the stage for therapeutic development for ASD, I developed a cortical spheroid model of the ECS – a three‑dimensional (3D) construct of neural cells derived from induced pluripotent stem cells (iPSCs) – and observed its electrophysiological properties using a bioelectronic assay.

The ECS helps to regulate synaptic plasticity, the mechanism by which the brain learns and changes during neurodevelopment and in response to life experiences. Endocannabinoids modulate communication between neurons, helping to refine complex brain circuitry that governs motivation and behaviour. As medicinal and recreational cannabis continues to gain favour around the world, it is more important than ever to study the neural mechanisms underlying the effects of cannabis on the developing nervous system, understand how dysregulation in the ECS contributes to developmental disorders such as ASD and identify potential targets for treatment.