THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders.
Boris Guennewig, Maina Bitar, Ifeanyi Obiorah, James B. Hanks, Elizabeth A O'Brien, Dominik C Kaczorowski, Yasmin L. Hurd, Panos Roussos, Kristen J Brennand, Guy Barry
Translational Psychiatry April 25, 2018 DOI: 10.1038/s41398-018-0137-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Human induced pluripotent stem cell-derived neurons |
| Intervention | Δ9-tetrahydrocannabinol (THC) |
| Topics | Cannabis |
| Key findings | The authors report that THC exposure, acute or chronic, dampened the neuronal transcriptional response to potassium chloride-induced depolarization and produced synaptic, mitochondrial, and glutamate signaling alterations. They suggest this blunted activation resembles effects previously observed in schizophrenia hiPSC-derived neurons, and that THC-related gene changes overlap with autism and intellectual disability pathways. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 3
- The antioxidant N-acetylcysteine prevents cortical neuropathological phenotypes caused by adolescent Δ-9-tetrahydrocannabinol exposure in male rats. Translational Psychiatry October 6, 2025
- Cannabis Use in Autism: Reasons for Concern about Risk for Psychosis Healthcare August 16, 2022
- Dual Transcriptomic and Epigenomic Signatures of THC Exposure in Human Prefrontal Cortex Development
Cites 7
- Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry April 1, 2016
- Functional effects of cannabinoids during dopaminergic specification of human neural precursors derived from induced pluripotent stem cells. Addiction Biology September 2017
- Association Between Cannabis and Psychosis: Epidemiologic Evidence. Biological Psychiatry April 1, 2016
- The Role of Endocannabinoid Signaling in Cortical Inhibitory Neuron Dysfunction in Schizophrenia. Biological Psychiatry April 1, 2016
- Cannabis and Psychosis: a Critical Overview of the Relationship. Current Psychiatry Reports February 1, 2016
and 2 more in the library