Adolescent THC exposure caused social memory deficits in mice through CB1 receptors on microglia, which triggered microglial cell death in the prefrontal cortex.
Neuroscientists, psychiatrists studying adolescent brain development, and cannabis risk researchers.
Microglial CB1 requiredfor THC-induced social memory deficits, with effects worsened by psychiatric risk gene 16p11.2 duplication
What the researchers found
Adolescent THC exposure caused microglial apoptosis in the medial prefrontal cortex, reducing excitability of pyramidal-tract neurons and producing adult social memory deficits, effects mediated by microglial CB1 receptors and exacerbated by 16p11.2 duplication.
Why it matters
This identifies microglia — the brain immune cells — as key mediators of adolescent cannabis harm, opening new avenues for understanding and potentially preventing cognitive damage from adolescent cannabis use.
The numbers in context
Effects mediated by microglial Cnr1 (CB1). Exacerbated in 16p11.2 duplication model (a psychiatric risk CNV). Changes in mPFC pyramidal-tract neuron excitability and adult social memory deficits.
How the study worked
Preclinical mouse study using adolescent THC exposure, 16p11.2 duplication genetic model, microglial-specific CB1 manipulation, electrophysiology, and social memory behavioral testing.
Who was studied
Mice with and without 16p11.2 duplication, exposed to THC during adolescence.
What this study cannot tell us
Mouse social memory may not directly translate to human cognitive function. 16p11.2 duplication is one of many genetic risk factors. Specific THC doses and timing may not reflect human use patterns.
How to read the evidence
Mechanistic preclinical study with genetic specificity; strong basic science evidence requiring human translation.
When this study was published
Recent mechanistic research on adolescent THC neurotoxicity.
The bigger picture
This study reveals that microglia, which prune synaptic connections during adolescent brain development, are a critical target of THC. This mechanism could explain why adolescent cannabis use is particularly harmful for genetically vulnerable individuals.
Replication
Novel mechanism identified; replication with different genetic models and THC protocols needed.
Funding
Not specified in abstract
Conflicts of interest
Not specified in abstract
Questions still open
- Could protecting microglia during adolescence prevent THC-induced cognitive damage?
- Do other genetic risk factors for psychiatric disorders similarly interact with adolescent THC exposure through microglia?
Read the original research
Microglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication.
Nature communications, 14(1), 6559
Citation
Hasegawa, Yuto; Kim, Juhyun; Ursini, Gianluca; Jouroukhin, Yan; Zhu, Xiaolei; Miyahara, Yu; Xiong, Feiyi; Madireddy, Samskruthi; Obayashi, Mizuho; Lutz, Beat; Sawa, Akira; Brown, Solange P; Pletnikov, Mikhail V; Kamiya, Atsushi. (2023). Microglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication.. Nature communications, 14(1), 6559. https://doi.org/10.1038/s41467-023-42276-5