A lab study exposing human iPSC-derived neurons to THC found that both acute and chronic exposure dampened the neuronal transcriptional response to stimulation, with gene expression changes overlapping with patterns seen in schizophrenia, autism, and intellectual disability.
Read this if you are interested in the molecular mechanisms connecting THC exposure to neuropsychiatric disorder risk.
THC-treated neurons showed gene expression patterns resembling schizophrenia patient neurons
What the researchers found
Researchers exposed neurons derived from human induced pluripotent stem cells (hiPSCs) to THC and analyzed the effects on gene expression.
Both acute and chronic THC exposure dampened the neurons' transcriptional response when stimulated with potassium chloride (which mimics neuronal activation). Essentially, THC-treated neurons failed to activate their genes appropriately in response to stimulation.
The gene expression changes in THC-treated neurons showed significant alterations in synaptic, mitochondrial, and glutamate signaling pathways. This blunted response pattern resembled effects previously observed in neurons derived from schizophrenia patients.
Additionally, the THC-affected genes showed significant overlap with genes associated with autism and intellectual disability, suggesting shared molecular pathways across neuropsychiatric disorders that are exacerbated by THC.
Why it matters
This study uses human neurons (derived from stem cells) rather than animal models, providing more relevant data on how THC affects human neural gene expression. The overlap between THC-induced changes and schizophrenia-associated patterns provides a molecular basis for understanding the cannabis-psychosis link.
The numbers in context
Both acute and chronic THC exposure tested. Significant alterations in synaptic, mitochondrial, and glutamate signaling genes. THC-affected genes overlapped with genes associated with schizophrenia, autism, and intellectual disability.
How the study worked
In vitro study using human iPSC-derived neurons exposed to THC acutely and chronically. RNA transcriptomic analysis compared gene expression profiles between THC-treated and vehicle-control neurons after potassium chloride-induced depolarization.
What this study cannot tell us
In vitro iPSC-derived neurons do not fully replicate the complexity of neurons in a living brain. THC concentrations used may not match physiological brain levels during actual cannabis use. The study cannot determine whether these gene expression changes are reversible. iPSC neurons may represent a developmental stage different from adult neurons.
How to read the evidence
In vitro study using human iPSC neurons provides preliminary evidence on molecular mechanisms, with relevance limited by the gap between cell culture and whole-brain effects.
When this study was published
Published in 2018. iPSC technology and transcriptomic analysis methods have advanced significantly since.
The bigger picture
This study provides cellular-level evidence for how THC might contribute to neuropsychiatric vulnerability. The finding that THC makes neurons respond more like schizophrenia-patient neurons suggests a convergent molecular mechanism, which could explain why cannabis use increases psychosis risk in genetically vulnerable individuals.
Questions still open
- Are the THC-induced gene expression changes reversible with cessation? Do individuals with schizophrenia risk genes show more pronounced responses to THC at the cellular level? Could CBD prevent these THC-induced transcriptomic changes?
Common questions
Does THC change how brain cells work?
Does this mean THC causes schizophrenia?
Read the original research
THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders.
Translational psychiatry, 8(1), 89
Citation
Guennewig, Boris; Bitar, Maina; Obiorah, Ifeanyi; Hanks, James; O'Brien, Elizabeth A; Kaczorowski, Dominik C; Hurd, Yasmin L; Roussos, Panos; Brennand, Kristen J; Barry, Guy. (2018). THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders.. Translational psychiatry, 8(1), 89. https://doi.org/10.1038/s41398-018-0137-3
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