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Cannabis and synaptic reprogramming of the developing brain

Abstract

Recent years have been transformational in regard to the perception of the health risks and benefits of cannabis with increased acceptance of use. This has unintended neurodevelopmental implications given the increased use of cannabis and the potent levels of Δ9-tetrahydrocannabinol today being consumed by pregnant women, young mothers and teens. In this Review, we provide an overview of the neurobiological effects of cannabinoid exposure during prenatal/perinatal and adolescent periods, in which the endogenous cannabinoid system plays a fundamental role in neurodevelopmental processes. We highlight impaired synaptic plasticity as characteristic of developmental exposure and the important contribution of epigenetic reprogramming that maintains the long-term impact into adulthood and across generations. Such epigenetic influence by its very nature being highly responsive to the environment also provides the potential to diminish neural perturbations associated with developmental cannabis exposure.

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Fig. 1: Neurodevelopmental pattern of the endocannabinoid system in humans and rodents.
Fig. 2: Impact of developmental THC exposure on synaptic plasticity in adulthood.
Fig. 3: Overview of proposed epigenetic effects induced by exogenous cannabinoids on the developing brain and epigenetic reprogramming of the germ line.

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Acknowledgements

The authors were supported by NIDA grants DA030359 and DA050403 (G.R.).

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Bara, A., Ferland, JM.N., Rompala, G. et al. Cannabis and synaptic reprogramming of the developing brain. Nat Rev Neurosci 22, 423–438 (2021). https://doi.org/10.1038/s41583-021-00465-5

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