The Role of Endocannabinniods in the Pathogenesis of Fetal Alcohol Syndrome

Taylor Jones

Introduction. Fetal alcohol syndrome is a congenital syndrome that is caused by excessive prenatal intake of alcohol during any trimester of pregnancy1. The global prevalence of FASD among children and youth in the general population was estimated to be 7.7 per 1000 population3. Alcohol is a teratogen that can cause variable physical and behavioral effects on the fetus and there is no amount of reported alcohol that is safe for the fetus. The most severe condition in this spectrum of diseases is known as fetal alcohol syndrome2. To properly combat this syndrome, we must first undercover the pathogenesis of the disease. Studies have shown that continuous ethanol exposure can lead to an upregulation in the endocannabinoid system which could possibly cause some of the negative effects seen with FAS2,4-7. Methods. The model for fetal alcohol syndrome was replicated in the mouse animal model. Anandamide, 2-arachidonylglycerol, and ERK1/2 from the hippocampus and neocortex were measured and compared by either one-way analysis of variance ANOVA or a two way ANOVA with Bonferroni’s post hoc test7. Results. Ethanol induces apoptotic neurodegeneration and enhances AEA in the P7 (postnatal mice seven which are similar to human neonates during the third trimester) mouse brain7. They also found that pharmacological inhibition or genetic deletion of CB1Rs provides protection against ethanol-induced activation of caspase-3 in the neonatal mouse brain7. It was also found that ERK1/2 promotes neuron cell growth and division, however the combination of CB1R and ethanol suppress it7. This causes neurons to undergo apoptosis. Conclusion. A combination of the previously mentioned effects will lead to a decrease in neuronal communication in the fetal brain which negatively affects cognitive functions such as learning and memory.


  1. Gupta, K., Gupta, V., & Shirasaka, T. (2016). An Update on Fetal Alcohol Syndrome-Pathogenesis, Risks, and Treatment [Abstract]. doi:10.1111/acer.13135
  2. Heller, M., & Burd, L. (2014). Review of ethanol dispersion, distribution, and elimination from the fetal alcohol syndrome [Abstract]. doi:10.1002/bdra.23232
  3. Lange,, Probst, C., Gmel, G., Rehm, J., Burd, L., & Popova, S. (2017). Global Prevalence of Fetal Alcohol Spectrum Disorder Among Children and Youth: A Systematic Review and Meta-analysis. [Abstract]. doi:10.1001/jamapediatrics.2017
  4. Seleverstov, O., Tobiasz, A., Jackson, J., Sullivan, R., Ma, D., Sullivan, J., . . . Bukiya, A. (2017). Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors. [Abstract]. doi:10.1016/j.alcohol.2017.01.014
  5. Subbanna, S., Nagre, N., Umapathy, N., Pace, B., & Basavarajappa, B. (2015). Ethanol Exposure Induces Neonatal Neurodegeneration by Enhancing CB1R Exon1 Histone H4K8 Acetylation and Upregulating CB1R Function causing Neurobehavioral Abnormalities in Adult Mice. International Journal of Neuropsychopharmacology, 18(4) doi:10.1093/ijnp/pyu028
  6. Subbanna, S., Psychoyos, D., Xie, S., & Basavarajappa, B. (2015). Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice. Journal of Neurochemistry, 134(2) doi:10.1111/jnc.13120
  7. Subbanna, S., Shivakumar, M., Psychoyos, D., Xie, S., & Basavarajappa, B. (2013). Anandamide-CB1 receptor signaling contributes to postnatal ethanol-induced neonatal neurodegeneration, adult synaptic, and memory deficits. The Journal of Neuroscience, 33(15) doi:10.1523/JNEUROSCI.3786-12.2013