Neuronal substrates and functional consequences of prenatal cannabis exposure

Abstract

Cannabis remains one of the world’s most widely used substance of abuse amongst pregnant women. Trends of the last 50 years show an increase in popularity in child-bearing women together with a constant increase in cannabis potency. In addition, potent herbal “legal” highs containing synthetic cannabinoids that mimic the effects of cannabis with unknown pharmacological and toxicological effects have gained rapid popularity amongst young adults. Despite the surge in cannabis use during pregnancy, little is known about the neurobiological and psychological consequences in the exposed offspring. In this review, we emphasize the importance of maternal programming, defined as the intrauterine presentation of maternal stimuli to the foetus, in neurodevelopment. In particular, we focus on cannabis-mediated maternal adverse effects, resulting in direct central nervous system alteration or sensitization to late-onset chronic and neuropsychiatric disorders. We compare clinical and preclinical experimental studies on the effects of foetal cannabis exposure until early adulthood, to stress the importance of animal models that permit the fine control of environmental variables and allow the dissection of cannabis-mediated molecular cascades in the developing central nervous system. In sum, we conclude that preclinical experimental models confirm clinical studies and that cannabis exposure evokes significant molecular modifications to neurodevelopmental programs leading to neurophysiological and behavioural abnormalities.

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Abbreviations

2-AG:

2-Arachidonoylglycerol

ABHD6:

α/β Hydrolase domain-containing 6 serine hydrolase

AEA:

Anandamide

CB1R:

Type 1 cannabinoid receptor

DAGLα/β:

Sn-1-Diacylglycerol lipase isoforms α/β

eCB:

Endocannabinoid

FAAH:

Fatty acid amide hydrolase

MAGL:

Monoacylglycerol lipase

NAPE:

N-acyl phosphatidylethanolamine

SCG10:

Super cervical ganglion-10

THC:

Δ9-Tetrahydrocannabinol

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Acknowledgment

This work was supported by the Swedish Medical Research Council (T.H), Swedish Brain Foundation (“Hjärnfonden”; T.H.), Novo Nordisk Foundation (Nordic Endocrinology Research Initiative; T.H.), the Petrus & Augusta Hedlunds Foundation (T.H.) and the National Institutes of Health (DA230214, T.H. & Y.L.H.; DA033660 Y.L.H.).

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Calvigioni, D., Hurd, Y.L., Harkany, T. et al. Neuronal substrates and functional consequences of prenatal cannabis exposure. Eur Child Adolesc Psychiatry 23, 931–941 (2014). https://doi.org/10.1007/s00787-014-0550-y

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Keywords

  • Foetal development
  • Endocannabinoid
  • THC
  • Neuropsychiatric disease