The Epigenetic Legacy of Illicit Drugs: Developmental Exposures and Late-life Phenotypes

Overview

Journal Environ Epigenet

Publisher Oxford University Press

Date 2019 Nov 29

PMID 31777665

Citations 15

Authors

Nicole M Wanner

Mathia L Colwell

Christopher Faulk

Affiliations

Soon will be listed here.

Abstract

The effects of exposure to illicit drugs on adult offspring are a significant and widespread but understudied global health concern, particularly in light of the growing opioid epidemic and emerging therapeutic uses for cannabis, ketamine, and MDMA. Epigenetic mechanisms including DNA methylation, histone modifications, and expression of non-coding RNAs provide a mechanistic link between the prenatal environment and health consequences years beyond the original exposure, and shifts in the epigenome present in early life or adolescence can lead to disease states only appearing during adulthood. The current review summarizes the literature assessing effects of perinatal illicit drug exposure on adult disease phenotypes as mediated by perturbations of the epigenome. Both behavioral and somatic phenotypes are included and studies reporting clinical data in adult offspring, epigenetic readouts in offspring of any age, or both phenotypic and epigenetic measures are prioritized. Studies of licit substances of abuse (i.e. alcohol, nicotine) are excluded with a focus on cannabis, psychostimulants, opioids, and psychedelics; current issues in the field and areas of interest for further investigation are also discussed.

Citing Articles

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Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans.

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Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes.

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References

McLaughlin P, Mactier H, Gillis C, Hickish T, Parker A, Liang W . Increased DNA Methylation of ABCB1, CYP2D6, and OPRM1 Genes in Newborn Infants of Methadone-Maintained Opioid-Dependent Mothers. J Pediatr. 2017; 190:180-184.e1. DOI: 10.1016/j.jpeds.2017.07.026. View

Martin A, Chao L . Semantic memory and the brain: structure and processes. Curr Opin Neurobiol. 2001; 11(2):194-201. DOI: 10.1016/s0959-4388(00)00196-3. View

Bergamaschi M, Queiroz R, Chagas M, de Oliveira D, De Martinis B, Kapczinski F . Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 2011; 36(6):1219-26. PMC: 3079847. DOI: 10.1038/npp.2011.6. View

Horvath S, Raj K . DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018; 19(6):371-384. DOI: 10.1038/s41576-018-0004-3. View

Lea A, Tung J, Archie E, Alberts S . Developmental plasticity: Bridging research in evolution and human health. Evol Med Public Health. 2018; 2017(1):162-175. PMC: 5798083. DOI: 10.1093/emph/eox019. View

Solowij N, Battisti R . The chronic effects of cannabis on memory in humans: a review. Curr Drug Abuse Rev. 2009; 1(1):81-98. DOI: 10.2174/1874473710801010081. View

Sundram S . Cannabis and neurodevelopment: implications for psychiatric disorders. Hum Psychopharmacol. 2006; 21(4):245-54. DOI: 10.1002/hup.762. View

Walker C, Ho S . Developmental reprogramming of cancer susceptibility. Nat Rev Cancer. 2012; 12(7):479-86. PMC: 3820510. DOI: 10.1038/nrc3220. View

Shalev I, Lerer E, Israel S, Uzefovsky F, Gritsenko I, Mankuta D . BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions. Psychoneuroendocrinology. 2008; 34(3):382-8. DOI: 10.1016/j.psyneuen.2008.09.017. View

10.

Zhao Q, Hou J, Chen B, Shao X, Zhu R, Bu Q . Prenatal cocaine exposure impairs cognitive function of progeny via insulin growth factor II epigenetic regulation. Neurobiol Dis. 2015; 82:54-65. DOI: 10.1016/j.nbd.2015.05.014. View

11.

Campos A, Moreira F, Gomes F, Del Bel E, Guimaraes F . Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci. 2012; 367(1607):3364-78. PMC: 3481531. DOI: 10.1098/rstb.2011.0389. View

12.

Molina-Holgado F, Alvarez F, Gonzalez I, Antonio M, Leret M . Maternal exposure to delta 9-tetrahydrocannabinol (delta 9-THC) alters indolamine levels and turnover in adult male and female rat brain regions. Brain Res Bull. 1997; 43(2):173-8. DOI: 10.1016/s0361-9230(96)00434-0. View

13.

Hunt R, Tzioumi D, Collins E, Jeffery H . Adverse neurodevelopmental outcome of infants exposed to opiate in-utero. Early Hum Dev. 2007; 84(1):29-35. DOI: 10.1016/j.earlhumdev.2007.01.013. View

14.

de Mello Schier A, de Oliveira Ribeiro N, Coutinho D, Machado S, Arias-Carrion O, Crippa J . Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa. CNS Neurol Disord Drug Targets. 2014; 13(6):953-60. DOI: 10.2174/1871527313666140612114838. View

15.

Skinner M, Guerrero-Bosagna C . Environmental signals and transgenerational epigenetics. Epigenomics. 2010; 1(1):111-117. PMC: 2886501. DOI: 10.2217/epi.09.11. View

16.

Hu Z, Chen K, Xia Z, Chavez M, Pal S, Seol J . Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging. Genes Dev. 2014; 28(4):396-408. PMC: 3937517. DOI: 10.1101/gad.233221.113. View

17.

Church M, Holmes P, Tilak J, Hotra J . Prenatal cocaine exposure influences the growth and life span of laboratory rats. Neurotoxicol Teratol. 2004; 26(3):429-41. DOI: 10.1016/j.ntt.2004.02.004. View

18.

Haj-Dahmane S, Shen R . Endocannabinoids suppress excitatory synaptic transmission to dorsal raphe serotonin neurons through the activation of presynaptic CB1 receptors. J Pharmacol Exp Ther. 2009; 331(1):186-96. PMC: 2766225. DOI: 10.1124/jpet.109.153858. View

19.

Nielsen D, Utrankar A, Reyes J, Simons D, Kosten T . Epigenetics of drug abuse: predisposition or response. Pharmacogenomics. 2012; 13(10):1149-60. PMC: 3463407. DOI: 10.2217/pgs.12.94. View

20.

Pothuizen H, Zhang W, Jongen-Relo A, Feldon J, Yee B . Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memory. Eur J Neurosci. 2004; 19(3):705-12. DOI: 10.1111/j.0953-816x.2004.03170.x. View