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

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

doi:10.3389/fnins.2023.1139309

Cited by 3 publications

(2 citation statements)

References 52 publications

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“…Diffusion Weighted Imaging -Quantitative Anisotropy Diffusion weighted imaging (DWI) was acquired with a spin-echo echo-planar-imaging (EPI) pulse sequence as previously described [33][34][35] having the following parameters: TR/TE = 500/20 ms, eight EPI segments, and 10 non-collinear gradient directions with a single b-value shell at 1000 s/mm 2 and one image with a B-value of 0 s/mm2 (referred to as B0). Geometrical parameters were: 48 coronal slices, each 0.313 mm thick (brain volume) and with in-plane resolution of 0.313×0.313 mm 2 (matrix size 96×96; FOV 30 mm 2 ).…”

Section: Voxel Based Morphometrymentioning

confidence: 99%

“…With respect to development, are the results unique to adolescence or would we have gotten similar or different data in middle aged adults or old mice? When adolescent, adult, and old mice are chronically exposed to the vapor of the same cannabis plant yielding similar blood levels of THC, each developmental period presents with different structural and functional data gleaned from multimodal MRI [32,34,35].…”

Section: Data Interpretation and Limitationsmentioning

confidence: 99%

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Changes in brain structure and function following exposure to oral LSD during adolescence: A multimodal MRI study

Harris,

Smith,

Ortiz

et al. 2024

Preprint

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Background: LSD is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. This is the first study to follow the developmental changes in brain structure and function following LSD exposure in periadolescence. Methods: Female and male mice were given vehicle, single or multiple treatments of 3.3 µg of LSD by oral gavage starting on postnatal day 51. Between postnatal days 90-120 mice were imaged and tested for cognitive and motor behavior. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. Results: Motor behavior and cognitive performance were unaffected by periadolescent exposure to LSD. Differences across experimental groups in brain volume for any of the 139 brain areas were few in number and not focused on any specific brain region. Multiple exposures to LSD significantly altered gray matter microarchitecture across much of the brain. These changes were primary associated with the thalamus, sensory and motor cortices, and basal ganglia. The forebrain olfactory system and prefrontal cortex and hindbrain cerebellum and brainstem were unaffected. The functional connectivity between forebrain white matter tracts and sensorimotor cortices and hippocampus was reduced with multidose LSD exposure. Conclusion: Does early exposure to LSD in periadolescence have lasting effects on brain development? There was no evidence of LSD having consequential effects on cognitive or motor behavior when animal were evaluated as young adults 90-120 days of age. Neither were there any differences in the volume of specific brain areas between experimental conditions. The pronounced changes in indices of anisotropy across much of the brain would suggest altered gray matter microarchitecture and neuroplasticity. The reduction in connectivity in forebrain white matter tracts with multidose LSD and consolidation around sensorimotor and hippocampal brain areas requires a battery of tests to understand the consequences of these changes on behavior.

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Section: Voxel Based Morphometrymentioning

confidence: 99%

Section: Data Interpretation and Limitationsmentioning

confidence: 99%

Changes in brain structure and function following exposure to oral LSD during adolescence: A multimodal MRI study

Harris,

Smith,

Ortiz

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Developmental changes in brain structure and function following exposure to oral LSD during adolescence

Harris-Blum,

Smith,

Ortiz

et al. 2024

Sci Rep

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LSD is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. This is the first study to follow the developmental changes in brain structure and function following LSD exposure in periadolescence. We hypothesized LSD given during a time of heightened neuroplasticity, particularly in the forebrain, would affect cognitive and emotional behavior and the associated underlying neuroanatomy and neurocircuitry. Female and male mice were given vehicle, single or multiple treatments of 3.3 µg of LSD by oral gavage starting on postnatal day 51. Between postnatal days 90–120 mice were imaged and tested for cognitive and motor behavior. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. Motor behavior and cognitive performance were unaffected by periadolescent exposure to LSD. Differences across experimental groups in brain volume for any of the 139 brain areas were few in number and not focused on any specific brain region. Multiple exposures to LSD significantly altered gray matter microarchitecture across much of the brain. These changes were primary associated with the thalamus, sensory and motor cortices, and basal ganglia. The forebrain olfactory system and prefrontal cortex and hindbrain cerebellum and brainstem were unaffected. The functional connectivity between forebrain white matter tracts and sensorimotor cortices and hippocampus was reduced with multidose LSD exposure. Does exposure to LSD in late adolescence have lasting effects on brain development? The bulk of our significant findings were seen through changes is DWI values across 74 brain areas in the multi-dose LSD group. The pronounced changes in indices of anisotropy across much of the brain would suggest altered gray matter microarchitecture and neuroplasticity. There was no evidence of LSD having consequential effects on cognitive or motor behavior when animal were evaluated as young adults 90–120 days of age. Neither were there any differences in the volume of specific brain areas between experimental conditions. The reduction in connectivity in forebrain white matter tracts with multidose LSD and consolidation around sensorimotor and hippocampal brain areas requires a battery of tests to understand the consequences of these changes on behavior.

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Chronic exposure to inhaled vaporized cannabis high in Δ9-THC suppresses Adderall-induced brain activity

Ognibene,

Desai,

Kulkarni

et al. 2024

Front. Pharmacol.

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BackgroundThere are increasing reports of the misuse of prescription psychostimulants for cognitive enhancement together with recreational cannabis. This raises a concern that chronic use of cannabis high in Δ9-THC may alter the sensitivity to amphetamines. In this exploratory study we hypothesized chronic exposure to Δ9-THC through vaporized cannabis would diminish the CNS activity of Adderall.MethodsTo address this issue we exposed male and female mice to inhaled vaporized cannabis (10.3% Δ9-THC) or placebo for 30 min each day for ten consecutive days. After 24 h, mice were imaged fully awake for changes in BOLD signal following an IP injection of Adderall (60 µg) during the scanning session. After a 2-week washout, without any cannabis or placebo exposure, mice were again imaged and challenged with Adderall during the scanning session. The data were registered to a mouse 3D MRI atlas with 134 brain regions providing site-specific increases and decreases in global brain activity.ResultsMice exposed to cannabis when compared to placebo showed a decrease in brain activation to Adderall. The blunted Adderall response was characterized by a decrease in positive BOLD signal and increase in negative BOLD. The prefrontal cortex, accumbens, ventral pallidum, caudate/putamen, and thalamus were most affected. After a 2-week wash out there were no significant differences between the cannabis and placebo groups when challenged with Adderall.SummaryThis exploratory study shows that short, daily exposures to inhaled cannabis, something equivalent to recreational use, affects the sensitivity to the psychostimulant Adderall. The reduced Adderall effect on brain activity, particularly circuitry associated with dopaminergic signaling raises concerns about escalation in psychostimulant use.

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

Cited by 3 publications

References 52 publications

Changes in brain structure and function following exposure to oral LSD during adolescence: A multimodal MRI study

Changes in brain structure and function following exposure to oral LSD during adolescence: A multimodal MRI study

Developmental changes in brain structure and function following exposure to oral LSD during adolescence

Chronic exposure to inhaled vaporized cannabis high in Δ9-THC suppresses Adderall-induced brain activity

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