Abstract
Endocannabinoids regulate brain development via modulating neural proliferation, migration,
and the differentiation of lineage-committed cells. In the fetal nervous system, (endo)cannabinoid-sensing
receptors and the enzymatic machinery of endocannabinoid metabolism exhibit a cellular
distribution map different from that in the adult, implying distinct functions. Notably,
cannabinoid receptors serve as molecular targets for the psychotropic plant-derived
cannabis constituent Δ9-tetrahydrocannainol, as well as synthetic derivatives (designer drugs). Over 180
million people use cannabis for recreational or medical purposes globally. Recreational
cannabis is recognized as a niche drug for adolescents and young adults. This review
combines data from human and experimental studies to show that long-term and heavy
cannabis use during pregnancy can impair brain maturation and predispose the offspring
to neurodevelopmental disorders. By discussing the mechanisms of cannabinoid receptor-mediated
signaling events at critical stages of fetal brain development, we organize histopathologic,
biochemical, molecular, and behavioral findings into a logical hypothesis predicting
neuronal vulnerability to and attenuated adaptation toward environmental challenges
(stress, drug exposure, medication) in children affected by in utero cannabinoid exposure.
Conversely, we suggest that endocannabinoid signaling can be an appealing druggable
target to dampen neuronal activity if pre-existing pathologies associate with circuit
hyperexcitability. Yet, we warn that the lack of critical data from longitudinal follow-up
studies precludes valid conclusions on possible delayed and adverse side effects.
Overall, our conclusion weighs in on the ongoing public debate on cannabis legalization,
particularly in medical contexts.
Keywords
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Article info
Publication history
Published online: September 23, 2015
Accepted:
September 14,
2015
Received in revised form:
August 26,
2015
Received:
March 18,
2015
Identification
Copyright
© 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
