Resting state functional connectivity in the default mode network: Relationships between cannabis use, gender, and cognition in adolescents and young adults

Ritchay, Megan M.; Huggins, Ashley A.; Wallace, A.; Larson, Christine L.; Lisdahl, Krista M.

doi:10.1016/j.nicl.2021.102664

Cited by 22 publications

(21 citation statements)

References 114 publications

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“…Previous studies have shown sex differences in neuropsychological functioning in adolescent and young adult cannabis users [ 90 ]. Our results are consistent with prior studies in cannabis using adolescents and adults that have shown alterations in brain structure, activity, and connectivity in cortical and cerebellar regions rich in CB 1 R in women that correlate with cognitive impairments and, in some cases, are directionally opposite from those found in men [ 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 ]. Of note, none of these prior reports identified sex-by-cannabis group differences in the insula, although one [ 98 ] did show higher cerebral blood flow in the insular cortex of males compared to females in both cannabis using and non-using control groups.…”

Section: Discussionsupporting

confidence: 92%

A Meta-Analysis of fMRI Studies of Youth Cannabis Use: Alterations in Executive Control, Social Cognition/Emotion Processing, and Reward Processing in Cannabis Using Youth

et al. 2022

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Background: Adolescent cannabis use (CU) is associated with adverse health outcomes and may be increasing in response to changing cannabis laws. Recent imaging studies have identified differences in brain activity between adult CU and controls that are more prominent in early onset users. Whether these differences are present in adolescent CU and relate to age/developmental stage, sex, or cannabis exposure is unknown. Methods: A systematic review and subsequent effect-size seed-based d mapping (SDM) meta-analysis were conducted to examine differences in blood-oxygen-level-dependent (BOLD) response during fMRI studies between CU and non-using typically developing (TD) youth. Supplemental analyses investigated differences in BOLD signal in CU and TD youth as a function of sex, psychiatric comorbidity, and the dose and severity of cannabis exposure. Results: From 1371 citations, 45 fMRI studies were identified for inclusion in the SDM meta-analysis. These studies compared BOLD response contrasts in 1216 CU and 1486 non-using TD participants. In primary meta-analyses stratified by cognitive paradigms, CU (compared to TD) youth showed greater activation in the rostral medial prefrontal cortex (rmPFC) and decreased activation in the dorsal mPFC (dmPFC) and dorsal anterior cingulate cortex (dACC) during executive control and social cognition/emotion processing, respectively. In meta-regression analyses and subgroup meta-analyses, sex, cannabis use disorder (CUD) severity, and psychiatric comorbidity were correlated with brain activation differences between CU and TD youth in mPFC and insular cortical regions. Activation differences in the caudate, thalamus, insula, dmPFC/dACC, and precentral and postcentral gyri varied as a function of the length of abstinence. Conclusions: Using an SDM meta-analytic approach, this report identified differences in neuronal response between CU and TD youth during executive control, emotion processing, and reward processing in cortical and subcortical brain regions that varied as a function of sex, CUD severity, psychiatric comorbidity, and length of abstinence. Whether aberrant brain function in CU youth is attributable to common predispositional factors, cannabis-induced neuroadaptive changes, or both warrants further investigation.

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Section: Discussionsupporting

confidence: 92%

A Meta-Analysis of fMRI Studies of Youth Cannabis Use: Alterations in Executive Control, Social Cognition/Emotion Processing, and Reward Processing in Cannabis Using Youth

et al. 2022

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“…Repeated use during adolescence may result in alterations in regions rich in eCB signaling, including the parietal cortex [ 10 , 11 , 12 ], a region that continues to develop into adolescence and underlies sustained attention [ 13 ]. Consistent with this, several neuropsychological studies have shown evidence that young regular cannabis users, typically defined as at least weekly cannabis use, have demonstrated poorer sustained and selective attention, attentional control, and increased lapses in attention [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Thus, repeated exposure to cannabis during the neurodevelopmental phase of adolescence may result in alterations in the attentional network.…”

Section: Introductionmentioning

confidence: 71%

Disrupted Resting State Attentional Network Connectivity in Adolescent and Young Adult Cannabis Users following Two-Weeks of Monitored Abstinence

et al. 2022

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Background. Numerous neuropsychological studies have shown that cannabis use during adolescence and young adulthood led to deficits in sustained and selective attention. However, few studies have examined functional connectivity in attentional networks among young cannabis users, nor have characterized relationships with cannabis use patterns following abstinence. Methods. Differences in resting state functional connectivity (RSFC) within the dorsal (DAN) and ventral (VAN) attention networks were examined in 36 adolescent and young adult cannabis users and 39 non-substance using controls following two weeks of monitored abstinence. Observed connectivity differences were then correlated with past-year and lifetime cannabis use, length of abstinence, age of regular use onset, and Cannabis Use Disorder symptoms (CUD). Results. After controlling for alcohol and nicotine use, cannabis users had lower RSFC within the DAN network, specifically between right inferior parietal sulcus and right anterior insula, as well as white matter, relative to controls. This region was associated with more severe cannabis use measures, including increased lifetime cannabis use, shorter length of abstinence, and more severe CUD symptoms. Conclusions. Findings demonstrate that regular cannabis use by adolescents and young adults is associated with subtle differences in resting state connectivity within the DAN, even after two weeks of monitored abstinence. Notably, more severe cannabis use markers (greater lifetime use, CUD symptoms, and shorter abstinence) were linked with this reduced connectivity. Thus, findings support public policy aimed at reducing and delaying cannabis use and treatments to assist with sustained abstinence. Future longitudinal studies are needed to investigate causation.

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“…There is compelling evidence in preclinical and clinical studies that chronic use of cannabis during adolescence and early adulthood can have detrimental effects on cognitive function and brain structure ( Ritchay et al, 2021 ). In contrast, translational research using healthy-aging, 18–24-month-old mice shows improved cognitive function to very low dose Δ9-THC ( Bilkei-Gorzo et al, 2017 ; Sarne et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of inhaled cannabis high in Δ9-THC or CBD on the aging brain: A translational MRI and behavioral study

Sadaka

Canuel

Febo

et al. 2023

Front. Aging Neurosci.

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With the recent legalization of inhaled cannabis for medicinal and recreational use, the elderly represents one of the newest, rapidly growing cohorts of cannabis users. To understand the neurobiological effects of cannabis on the aging brain, 19–20 months old mice were divided into three groups exposed to vaporized cannabis containing ~10% Δ9-THC, ~10% CBD, or placebo for 30 min each day. Voxel based morphometry, diffusion weighted imaging, and resting state functional connectivity data were gathered after 28 days of exposure and following a two-week washout period. Tail-flick, open field, and novel object preference tests were conducted to explore analgesic, anxiolytic, and cognitive effects of cannabis, respectively. Vaporized cannabis high in Δ9-THC and CBD achieved blood levels reported in human users. Mice showed antinociceptive effects to chronic Δ9-THC without tolerance while the anxiolytic and cognitive effects of Δ9-THC waned with treatment. CBD had no effect on any of the behavioral measures. Voxel based morphometry showed a decrease in midbrain dopaminergic volume to chronic Δ9-THC followed but an increase after a two-week washout. Fractional anisotropy values were reduced in the same area by chronic Δ9-THC, suggesting a reduction in gray matter volume. Cannabis high in CBD but not THC increased network strength and efficiency, an effect that persisted after washout. These data would indicate chronic use of inhaled cannabis high in Δ9-THC can be an effective analgesic but not for treatment of anxiety or cognitive decline. The dopaminergic midbrain system was sensitive to chronic Δ9-THC but not CBD showing robust plasticity in volume and water diffusivity prior to and following drug cessation an effect possibly related to the abuse liability of Δ9-THC. Chronic inhaled CBD resulted in enhanced global network connectivity that persisted after drug cessation. The behavioral consequences of this sustained change in brain connectivity remain to be determined.

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Resting state functional connectivity in the default mode network: Relationships between cannabis use, gender, and cognition in adolescents and young adults

Cited by 22 publications

References 114 publications

A Meta-Analysis of fMRI Studies of Youth Cannabis Use: Alterations in Executive Control, Social Cognition/Emotion Processing, and Reward Processing in Cannabis Using Youth

A Meta-Analysis of fMRI Studies of Youth Cannabis Use: Alterations in Executive Control, Social Cognition/Emotion Processing, and Reward Processing in Cannabis Using Youth

Disrupted Resting State Attentional Network Connectivity in Adolescent and Young Adult Cannabis Users following Two-Weeks of Monitored Abstinence

Effects of inhaled cannabis high in Δ9-THC or CBD on the aging brain: A translational MRI and behavioral study

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