Dataset Information

Miswiring the brain: Human prenatal Δ9-tetrahydrocannabinol use associated with altered fetal hippocampal brain network connectivity.

ABSTRACT: Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in human brain hippocampal functional connectivity prior to birth. Prenatal drug toxicology and fetal fMRI data were available in a sample of 115 fetuses [43 % female; mean age 32.2 weeks (SD = 4.3)]. Voxelwise hippocampal connectivity analysis in a subset of age and sex-matched fetuses revealed that PCE was associated with alterations in fetal dorsolateral, medial and superior frontal, insula, anterior temporal, and posterior cingulate connectivity. Classification of group differences by age 5 outcomes suggest that compared to the non-PCE group, the PCE group is more likely to have increased connectivity to regions associated with less favorable outcomes and to have decreased connectivity to regions associated with more favorable outcomes. This is preliminary evidence that altered fetal neural connectome may contribute to neurobehavioral vulnerability observed in children exposed to cannabis in utero.

SUBMITTER: Thomason ME

PROVIDER: S-EPMC8363827 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Miswiring the brain: Human prenatal Δ9-tetrahydrocannabinol use associated with altered fetal hippocampal brain network connectivity.

Thomason Moriah E ME Palopoli Ava C AC Jariwala Nicki N NN Werchan Denise M DM Chen Alan A Adhikari Samrachana S Espinoza-Heredia Claudia C Brito Natalie H NH Trentacosta Christopher J CJ

Developmental cognitive neuroscience 20210806

Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in ...[more]

PMID: 34388638

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Project description:ImportanceControlled clinical laboratory studies have shown that cannabidiol (CBD) can sometimes attenuate or exacerbate the effects of Δ9-tetrahydrocannabinol (Δ9-THC). No studies have evaluated differences in pharmacokinetics (PK) of Δ9-THC and pharmacodynamics (PD) between orally administered cannabis extracts that vary with respect to Δ9-THC and CBD concentrations.ObjectiveTo compare the PK and PD of orally administered Δ9-THC-dominant and CBD-dominant cannabis extracts that contained the same Δ9-THC dose (20 mg).Design, setting, and participantsThis randomized clinical trial was a within-participant, double-blind, crossover study conducted from January 2021 to March 2022 at the Johns Hopkins University Behavioral Pharmacology Research Unit, Baltimore, MD. Eighteen healthy adults completed 3 randomized outpatient experimental test sessions that were each separated by at least 1 week.InterventionsBrownies containing (1) no cannabis extract (ie, placebo); (2) Δ9-THC-dominant extract (20 mg Δ9-THC with no CBD); and (3) CBD-dominant extract (20 mg Δ9-THC + 640 mg CBD) were administered to participants 30 minutes prior to administering a cytochrome P450 (CYP) probe drug cocktail, which consisted of 100 mg caffeine, 20 mg omeprazole, 25 mg losartan, 30 mg dextromethorphan, and 2 mg midazolam.Main outcomes and measuresChange-from-baseline plasma concentrations for Δ9-THC or Δ9-THC metabolites and scores for subjective drug effects, cognitive and psychomotor performance, and vital signs. The area under the plasma vs concentration vs time curve (AUC) and maximum plasma concentration (Cmax) were determined.ResultsThe participant cohort of 18 adults included 11 males (61.1%) and 7 females (38.9%) with a mean (SD) age of 30 (7) years who had not used cannabis for at least 30 days prior to initiation of the study (mean [SD] day since last cannabis use, 86 [66] days). The CYP cocktail + placebo brownie and the CYP cocktail did not affect any PD assessments. Relative to CYP cocktail + Δ9-THC, CYP cocktail + Δ9-THC + CBD produced a higher Cmax and area under the plasma concentration vs time curve for Δ9-THC, 11-OH-Δ9-THC, and Δ9-THC-COOH. The CYP cocktail + Δ9-THC + CBD increased self-reported anxiety, sedation, and memory difficulty, increased heart rate, and produced a more pronounced impairment of cognitive and psychomotor performance compared with both CYP cocktail + Δ9-THC and CYP cocktail + placebo.Conclusions and relevanceIn this randomized clinical trial of oral Δ9-THC and CBD, stronger adverse effects were elicited from a CBD-dominant cannabis extract compared with a Δ9-THC-dominant cannabis extract at the same Δ9-THC dose, which contradicts common claims that CBD attenuates the adverse effects of Δ9-THC. CBD inhibition of Δ9-THC and 11-OH-Δ9-THC metabolism is the likely mechanism for the differences observed. An improved understanding of cannabinoid-cannabinoid and cannabinoid-drug interactions are needed to inform clinical and regulatory decision-making regarding the therapeutic and nontherapeutic use of cannabis products.Trial registrationclinicaltrials.gov Identifier: NCT04201197.

Dataset Information

Miswiring the brain: Human prenatal Δ9-tetrahydrocannabinol use associated with altered fetal hippocampal brain network connectivity.

Publications

Miswiring the brain: Human prenatal Δ9-tetrahydrocannabinol use associated with altered fetal hippocampal brain network connectivity.

Similar Datasets

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