Prenatal cannabis exposure can complicate in utero development of the nervous system. Cannabis impacts the formation and functions of neuronal circuitries by targeting cannabinoid receptors. Endocannabinoid signaling emerges as a signaling cassette that orchestrates neuronal differentiation programs through the precisely timed interaction of endocannabinoid ligands with their cognate cannabinoid receptors. By indiscriminately prolonging the 'switched-on' period of cannabinoid receptors, cannabis can hijack endocannabinoid signals to evoke molecular rearrangements, leading to the erroneous wiring of neuronal networks. Here, we formulate a hierarchical network design necessary and sufficient to describe the molecular underpinnings of cannabis-induced neural growth defects. We integrate signalosome components, deduced from genome- and proteome-wide arrays and candidate analyses, to propose a mechanistic hypothesis of how cannabis-induced ectopic cannabinoid receptor activity overrides physiological neurodevelopmental endocannabinoid signals, affecting the timely formation of synapses.
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