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Chronic exposure to inhaled vaporized cannabis high in Δ9-THC alters brain structure in adult female mice.

Autumn Taylor, Amanda Nweke, Veniesha Vincent, Marvellous Oke, Praveen P Kulkarni, Craig F. Ferris

Frontiers in Neuroscience 2023 DOI: 10.3389/fnins.2023.1139309 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Exploratory experimental animal study Peer reviewed
Population Adult female mice
Interventions Vaporized cannabis (10.3% THC and 0.05% CBD) Placebo
Dose 10.3% THC and 0.05% CBD
Duration 21 days of daily exposure
Measures Voxel-based morphometry, Diffusion weighted imaging MRI
Topics Cannabis
Keywords Diffusion weighted imaging Dopaminergic system Limbic cortex Prefrontal cortex pfc Voxel-based morphometry
Key findings Daily vaporized cannabis exposure for 21 days was associated with volumetric changes in forebrain regions including the prefrontal cortex, accumbens, ventral pallidum, and limbic cortex, with matching changes in water diffusivity suggesting altered gray matter microarchitecture. The authors argue these findings are consistent with clinical cannabis use disorder data and that dopaminergic sensitivity raises concerns about abuse liability in drug-naive adult females starting chronic use.

Abstract

The medical and recreational use of cannabis has increased in the United States. Its chronic use can have detrimental effects on the neurobiology of the brain-effects that are age-dependent. This was an exploratory study looking at the effects of chronically inhaled vaporized cannabis on brain structure in adult female mice. Adult mice were exposed daily to vaporized cannabis (10.3% THC and 0.05% CBD) or placebo for 21 days. Following cessation of treatment mice were examined for changes in brain structure using voxel-based morphometry and diffusion weighted imaging MRI. Data from each imaging modality were registered to a 3D mouse MRI atlas with 139 brain areas. Mice showed volumetric changes in the forebrain particularly the prefrontal cortex, accumbens, ventral pallidum, and limbic cortex. Many of these same brain areas showed changes in water diffusivity suggesting alterations in gray matter microarchitecture. These data are consistent with much of the clinical findings on cannabis use disorder. The sensitivity of the dopaminergic system to the daily exposure of vaporized cannabis raises concerns for abuse liability in drug naïve adult females that initiate chronic cannabis use.

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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