Adolescent THC exposure combined with genetic psychiatric risk (Reelin deficiency) disrupted neuroblast migration programs in the nucleus accumbens, potentially impairing GABAergic circuit maturation.
Psychiatric researchers, developmental neuroscientists, parents and clinicians concerned about adolescent cannabis use, and genomics researchers.
What the researchers found
Single-nucleus RNA sequencing identified a gene co-expression network affected by both Reelin genotype and THC, enriched in psychiatric disorder genes and expressed in GABAergic neuroblasts. These neuroblasts actively migrate during adolescence and receive cues from cannabinoid receptor-expressing interneurons, revealing a mechanism for gene-environment interaction in psychosis risk.
Why it matters
This provides a molecular explanation for why adolescent cannabis use increases psychiatric risk — THC disrupts the migration of specific brain cells during a critical developmental window, and genetic vulnerability amplifies this effect.
The numbers in context
Identified gene network enriched in human psychiatric disorder genes. Neuroblasts actively migrated in adolescent NAc but declined with age. Cholecystokinin interneurons with high CB1 expression provided migratory cues.
How the study worked
Single-nucleus RNA sequencing of nucleus accumbens in Reelin haploinsufficient mice with adolescent THC exposure, combined with cell-to-cell communication analysis and migration assays across development.
What this study cannot tell us
Mouse model with a single genetic risk factor — human psychiatric vulnerability is polygenic. Single-nucleus sequencing provides a snapshot, not a timeline. Reln haploinsufficiency is one of many risk models.
How to read the evidence
Cutting-edge single-nucleus transcriptomics providing novel mechanistic insights, but single genetic model in mice limits direct clinical translation.
When this study was published
Recent study using state-of-the-art single-cell methods to reveal how adolescent cannabis interacts with genetic risk at the molecular level.
The bigger picture
The gene-environment interaction between cannabis and psychiatric risk has been observed epidemiologically but lacked a molecular mechanism. This study fills that gap by showing how THC disrupts a specific developmental process in genetically vulnerable individuals.
Questions still open
- Could genetic screening identify adolescents at highest risk for cannabis-induced psychiatric effects? Is the critical window for neuroblast migration vulnerability the same in humans as mice?
Common questions
Why is teen cannabis use especially risky?
Does genetics affect cannabis risk?
Read the original research
Single-Nucleus Transcriptomics Identifies Neuroblast Migration Programs Sensitive to Reelin and Cannabis in the Adolescent Nucleus Accumbens.
bioRxiv : the preprint server for biology
Citation
Zuo, Yanning; Formoli, Numaan; Libster, Avraham; Sun, Daimeng; Turner, Andrew; Iemolo, Attilio; Telese, Francesca. (2025). Single-Nucleus Transcriptomics Identifies Neuroblast Migration Programs Sensitive to Reelin and Cannabis in the Adolescent Nucleus Accumbens.. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2025.04.03.646846
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