Molecular model of cannabis sensitivity in developing neuronal circuits

Trends Pharmacol Sci. 2011 Sep;32(9):551-61. doi: 10.1016/ Epub 2011 Jul 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cannabinoid Receptor Modulators / metabolism
  • Cannabis / chemistry*
  • Female
  • Humans
  • Marijuana Abuse / complications*
  • Maternal-Fetal Exchange
  • Models, Molecular*
  • Neurons / drug effects
  • Neurons / metabolism
  • Pregnancy
  • Receptors, Cannabinoid / metabolism
  • Signal Transduction / drug effects


  • Cannabinoid Receptor Modulators
  • Receptors, Cannabinoid