There is a strong association between cannabis use and schizophrenia but the underlying cellular links are poorly understood. Neurons derived from human-induced pluripotent stem cells (hiPSCs) offer a platform for investigating both baseline and dynamic changes in human neural cells. Here, we exposed neurons derived from hiPSCs to Δ⁹-tetrahydrocannabinol (THC), and identified diagnosis-specific differences not detectable in vehicle-controls. RNA transcriptomic analyses revealed that THC administration, either by acute or chronic exposure, dampened the neuronal transcriptional response following potassium chloride (KCl)-induced neuronal depolarization. THC-treated neurons displayed significant synaptic, mitochondrial, and glutamate signaling alterations that may underlie their failure to activate appropriately; this blunted response resembles effects previously observed in schizophrenia hiPSC- derived neurons. Furthermore, we show a significant alteration in THC-related genes associated with autism and intellectual disability, suggesting shared molecular pathways perturbed in neuropsychiatric disorders that are exacerbated by THC.

Source: https://pubmed.ncbi.nlm.nih.gov/29691375/?utm_source=no_user_agent&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1z7zlNEMzQex5jriqkhCblNtckSEpT9xYlxxeymU_73UTETESY&fc=20200804213258&ff=20200810102726&v=2.11.5