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Study breakdown

Adolescent cannabis vapor exposure produced opposite brain changes in male and female mice on MRI

Animal StudyModerate evidence
The takeaway

Chronic inhaled cannabis vapor during adolescence produced sexually dimorphic brain changes in mice: females showed altered grey matter structure in forebrain and hindbrain, while males showed disrupted functional connectivity in hippocampal circuits and cognitive deficits.

Neuroscientists, adolescent health researchers, and parents concerned about teen cannabis use.

Opposite brain changes: structural in females, functional in males

What the researchers found

Female mice showed altered fractional anisotropy and apparent diffusion coefficient (measures of brain microstructure) in forebrain and hindbrain. Males showed increased functional coupling with thalamus, hypothalamus, and brainstem reticular activating system, altered hippocampal connectivity, and deficits in novel object recognition. The effects were sexually dimorphic with minimal overlap.

Why it matters

This is one of the first studies to use clinically relevant inhaled cannabis vapor (rather than injected THC) with multimodal brain imaging in adolescent animals, providing data more translatable to human adolescent cannabis use.

The numbers in context

Daily exposure from postnatal day 23-51; 10.3% THC cannabis; 139 brain areas analyzed via 3D atlas; males showed cognitive deficits on novel object recognition.

How the study worked

Female and male mice were exposed daily to vaporized cannabis (10.3% THC, 0.05% CBD) or placebo from postnatal day 23-51 (periadolescence). After cessation, multimodal MRI (voxel-based morphometry, diffusion-weighted imaging, resting-state functional connectivity) was performed using a 3D atlas with 139 brain regions. Novel object preference tested.

What this study cannot tell us

Mouse model may not fully translate to humans. Single cannabis concentration tested. Only one cognitive test used. No dose-response or duration comparisons. Short-term follow-up after cessation.

How to read the evidence

Rigorous multimodal MRI study with clinically relevant inhaled cannabis, but animal model with single concentration.

When this study was published

Published in 2022.

The bigger picture

The finding that adolescent cannabis affects male and female brains in completely different ways has implications for sex-specific risk assessment and challenges the one-size-fits-all approach to cannabis education.

Questions still open

  • Do these sex differences persist into adulthood or resolve? Would lower THC concentrations produce similar effects? Are the female structural changes or male functional changes more clinically relevant?

Common questions

Does cannabis affect male and female brains differently?
In this mouse study, yes. Adolescent cannabis exposure changed brain structure in females (grey matter microarchitecture in forebrain and hindbrain) but altered brain connectivity in males (hippocampal circuits and brainstem coupling), with males also showing cognitive deficits.
Why is this study more relevant than older animal research?
This study used inhaled vaporized cannabis rather than injected THC, better mimicking how humans actually consume cannabis. It also used multimodal MRI to examine both brain structure and function across 139 brain regions.

Read the original research

Changes in brain structure and function following chronic exposure to inhaled vaporised cannabis during periadolescence in female and male mice: A multimodal MRI study.

Addiction biology, 27(3), e13169

Citation

Coleman, James R; Madularu, Dan; Ortiz, Richard J; Athanassiou, Maria; Knudsen, Alexa; Alkislar, Ilayda; Cai, Xuezhu; Kulkarni, Praveen P; Cushing, Bruce S; Ferris, Craig F. (2022). Changes in brain structure and function following chronic exposure to inhaled vaporised cannabis during periadolescence in female and male mice: A multimodal MRI study.. Addiction biology, 27(3), e13169. https://doi.org/10.1111/adb.13169

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