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Neurobiological consequences of maternal cannabis on human fetal development and its neuropsychiatric outcome

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Abstract

Despite the high prevalence of marijuana use among pregnant women and adolescents, the impact of cannabis on the developing brain is still not well understood. However, growing evidence supports that the endocannabinoid system plays a major role in CNS patterning in structures relevant for mood, cognition, and reward, such as the mesocorticolimbic system. It is thus clear that exposure to cannabis during early ontogeny is not benign and potential compensatory mechanisms that might be expected to occur during neurodevelopment appear insufficient to eliminate vulnerability to neuropsychiatric disorders in certain individuals. Both human longitudinal cohort studies and animal models strongly emphasize the long-term influence of prenatal cannabinoid exposure on behavior and mental health. This review provides an overview of the endocannabinoid system and examines the neurobiological consequences of cannabis exposure in pregnancy and early life by addressing its impact on the development of neurotransmitters systems relevant to neuropsychiatric disorders and its association with these disorders later in life. It posits that studying in utero cannabis exposure in association with genetic mutations of neural systems that have strong relationships to endocannabinoid function, such as the dopamine, opioid, glutamate, and GABA, might help to identify individuals at risk. Such data could add to existing knowledge to guide public health platform in regard to the use of cannabis and its derivatives during pregnancy.

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Abbreviations

2-AG:

2-Arachidonoyl glycerol

5HT3:

5-hydroxytryptamine 3 receptor

AAT:

Adenosine-adenosine-thymine

ABHD4:

Alpha/beta hydroxylase-4

AEA:

Anandamide

AMPA:

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

CB1R:

Cannabinoid receptor type 1

CB2R:

Cannabinoid receptor type 2

CNR1:

Cannabinoid receptor type 1 gene

CNS:

Central nervous system

COMT:

Catechol-O-methyltransferase

D1 :

Dopamine receptor type 1

D2 :

Dopamine receptor type 2

DAGL:

Diacylglycerol lipase

eCB:

Endocannabinoid

FAAH:

Fatty acid amide hydrolase

GABA:

Gamma-aminobutyric acid

GABA-B:

Gamma-aminobutyric acid type B receptor

GDE1:

Glycerophosphodiester phosphodiesterase 1

GluR1:

Glutamate receptor type 1

GluR2/3:

Glutamate receptor type 2 and 3

GPCR:

G protein-coupled receptor

GPR55:

G-protein coupled receptor 55

GTPγS:

Guanosine gamma thio-phosphate

IQ:

Intelligence quotient

MAPK:

Mitogen-activated protein kinase

Met:

Methionine

MGL:

Monoglyceride lipase

MHPCD:

Maternal Health Practices and Child Development Project

mRNA:

Messenger ribonucleic acid

NAPE-PLD:

N-acyl-phosphatidylethanolamine-specific phospholipase D

NRG1:

Neuregulin 1

OPPS:

Ottawa Prenatal Prospective Study

THC:

Δ9-tetrahydrocannabinol

TRPV1:

Transient receptor potential vanilloid 1

Val:

Valine

WIN55,212-2:

R(+)-[2,3-Dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo [1,2,3-de]1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate

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Acknowledgments

This work was supported by DA01230 (YH) and DA023214 (YH, TH), the Swedish Medical Research Council K2008-66X-20762-01-3 (T.H.), Scottish Universities Life Science Alliance (SULSA, T.H.), the European Molecular Biology Organization Young Investigator Programme (T.H.), and a Research Fellowship Award from the Centre Hospitalier de l’Université de Montréal (DJA).

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Jutras-Aswad, D., DiNieri, J.A., Harkany, T. et al. Neurobiological consequences of maternal cannabis on human fetal development and its neuropsychiatric outcome. Eur Arch Psychiatry Clin Neurosci 259, 395–412 (2009). https://doi.org/10.1007/s00406-009-0027-z

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