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

James R Coleman, Dan Madularu, Richard J. Ortiz, Maria Athanassiou, Alexa Knudsen, Ilayda Alkislar, Xuezhu Cai, Praveen P Kulkarni, Bruce S Cushing, Craig F. Ferris

Addiction Biology May 2022 DOI: 10.1111/adb.13169 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Controlled experimental animal study Peer reviewed
Population Adolescent female and male mice
Interventions Vaporised cannabis (10.3% Δ-9-tetrahydrocannabinol [THC] and 0.05% cannabidiol [CBD]) placebo
Dose 10.3% Δ-9-tetrahydrocannabinol [THC] and 0.05% cannabidiol [CBD]
Duration Postnatal day 23 to day 51
Measures voxel-based morphometry, diffusion weighted imaging, resting state functional connectivity, novel object preference test
Topics Cannabis
Keywords Cb1 Diffusion weighted imaging Endocannabinoid Hippocampus Voxel-based morphometry
Key findings Chronic vaporised cannabis exposure in adolescent mice produced sexually dimorphic effects: females showed an inverse correlation between fractional anisotropy and apparent diffusion coefficient in forebrain and hindbrain, while males showed increased functional coupling with the thalamus, hypothalamus and brainstem reticular activating system, altered hippocampal coupling, and deficits in object recognition.

Abstract

Social norms and legality surrounding the use of medical and recreational cannabis are changing rapidly. The prevalence of cannabis use in adolescence is increasing. The aim of this study was to assess any sex-based neurobiological effects of chronically inhaled, vaporised cannabis on adolescent female and male mice. Female and male mice were exposed daily to vaporised cannabis (10.3% Δ-9-tetrahydrocannabinol [THC] and 0.05% cannabidiol [CBD]) or placebo from postnatal day 23 to day 51. Following cessation of treatment, mice were examined for changes in brain structure and function using noninvasive multimodal magnetic resonance imaging (MRI). Data from voxel-based morphometry, diffusion weighted imaging and rest state functional connectivity were registered to and analysed with a 3D mouse atlas with 139 brain areas. Following imaging, mice were tested for their preference for a novel object. The effects were sexually dimorphic with females showing a unique distribution and inverse correlation between measures of fractional anisotropy and apparent diffusion coefficient localised to the forebrain and hindbrain. In contrast males displayed significant increased functional coupling with the thalamus, hypothalamus and brainstem reticular activating system as compared with controls. Cannabis males also presented with altered hippocampal coupling and deficits in cognitive function. Chronic exposure to inhaled vaporised cannabis had significant effects on brain structure and function in early adulthood corroborating much of the literature. Females presented with changes in grey matter microarchitecture, while males showed altered functional connectivity in hippocampal circuitry and deficits in object recognition.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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