title: Molecular model of cannabis sensitivity in developing neuronal circuits.
abstract: 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.
authors.affiliation: European Neuroscience Institute at Aberdeen, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: Erik
authors.initials: E
authors.lastname: Keimpema
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.forename: Tibor
authors.initials: T
authors.lastname: Harkany
mesh_terms: D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D002188:Cannabis / Q000737:chemistry*; D005260:Female; D006801:Humans; D002189:Marijuana Abuse / Q000150:complications*; D008431:Maternal-Fetal Exchange; D008958:Models, Molecular; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D043882:Receptors, Cannabinoid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D063385:Cannabinoid Receptor Modulators; D043882:Receptors, Cannabinoid