{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:06:35Z","timestamp":1790175995447,"version":"4.1.0"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T00:00:00Z","timestamp":1590105600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T00:00:00Z","timestamp":1590105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Envir Health Rpt"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Purpose of Review<\/jats:title>\n<jats:p>Cannabis exposure during critical windows of development may have intergenerational physiological consequences disrupting epigenetic programming and marks. This review examines the literature relating to pre-gestational and prenatal cannabinoid exposure and its effect on genes and molecular pathways related to the development of psychiatric disease.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Recent Findings<\/jats:title>\n<jats:p>Developmental cannabis exposure alters epigenetic processes with functional gene consequences. These include potentially heritable alterations in genes and molecular pathways critical for brain development and associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia, addiction, and other psychiatric diseases.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Summary<\/jats:title>\n<jats:p>Cannabis consumption and mental health illness in adolescents and young adults are increasing in the United States (U.S.), and recent studies suggest that cannabis consumption during critical periods of brain development could contribute to mental health illness through epigenetic mechanisms. These findings warrant future studies and consideration by regulators and health communicators.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s40572-020-00275-4","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T23:05:37Z","timestamp":1590102337000},"page":"325-342","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Cannabis Exposure During Critical Windows of Development: Epigenetic and Molecular Pathways Implicated in Neuropsychiatric Disease"],"prefix":"10.1007","volume":"7","author":[{"given":"Anna","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farla","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha S.","family":"Sandy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Cardenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,22]]},"reference":[{"key":"275_CR1","unstructured":"Bose J Key Substance Use and Mental Health Indicators in the United States: Results from the 2017 National Survey on Drug Use and Health. 2017:124."},{"issue":"12","key":"275_CR2","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1111\/add.13886","volume":"112","author":"R Smart","year":"2017","unstructured":"Smart R, Caulkins JP, Kilmer B, Davenport S, Midgette G. Variation in cannabis potency and prices in a newly legal market: evidence from 30 million cannabis sales in Washington state: legal cannabis potency and price variation. Addiction. 2017;112(12):2167\u201377. https:\/\/doi.org\/10.1111\/add.13886.","journal-title":"Addiction."},{"key":"275_CR3","unstructured":"DrugFacts: Nationwide Trends | National Institute on Drug Abuse (NIDA)."},{"key":"275_CR4","unstructured":"Marijuana Use in Adolescence. HHSgov. 2018."},{"issue":"2","key":"275_CR5","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1001\/jama.2019.7982","volume":"322","author":"ND Volkow","year":"2019","unstructured":"Volkow ND, Han B, Compton WM, McCance-Katz EF. Self-reported medical and nonmedical cannabis use among pregnant women in the United States. JAMA. 2019;322(2):167\u20139. https:\/\/doi.org\/10.1001\/jama.2019.7982.","journal-title":"JAMA."},{"issue":"10","key":"275_CR6","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1016\/S2215-0366(16)30208-5","volume":"3","author":"WM Compton","year":"2016","unstructured":"Compton WM, Han B, Jones CM, Blanco C, Hughes A. Marijuana use and use disorders in adults in the USA, 2002\u201314: analysis of annual cross-sectional surveys. Lancet Psychiatry. 2016;3(10):954\u201364. https:\/\/doi.org\/10.1016\/S2215-0366(16)30208-5.","journal-title":"Lancet Psychiatry"},{"issue":"5","key":"275_CR7","doi-asserted-by":"publisher","first-page":"282","DOI":"10.7326\/M18-0810","volume":"169","author":"S Keyhani","year":"2018","unstructured":"Keyhani S, Steigerwald S, Ishida J, Vali M, Cerd\u00e1 M, Hasin D, et al. Risks and benefits of marijuana Use: A National Survey of U.S. Adults. Ann Intern Med. 2018;169(5):282. https:\/\/doi.org\/10.7326\/M18-0810.","journal-title":"Ann Intern Med"},{"issue":"6","key":"275_CR8","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1177\/2045125312457586","volume":"2","author":"Z Atakan","year":"2012","unstructured":"Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol. 2012;2(6):241\u201354. https:\/\/doi.org\/10.1177\/2045125312457586.","journal-title":"Ther Adv Psychopharmacol"},{"issue":"4","key":"275_CR9","first-page":"149","volume":"7","author":"P Sharma","year":"2012","unstructured":"Sharma P, Murthy P, Bharath MMS. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149\u201356.","journal-title":"Iran J Psychiatry"},{"issue":"7","key":"275_CR10","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00406-009-0027-z","volume":"259","author":"D Jutras-Aswad","year":"2009","unstructured":"Jutras-Aswad D, DiNieri JA, Harkany T, Hurd YL. Neurobiological consequences of maternal cannabis on human fetal development and its neuropsychiatric outcome. Eur Arch Psychiatry Clin Neurosci. 2009;259(7):395\u2013412. https:\/\/doi.org\/10.1007\/s00406-009-0027-z.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"issue":"4","key":"275_CR11","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/s0306-4522(97)00348-5","volume":"82","author":"NE Buckley","year":"1998","unstructured":"Buckley NE, Hansson S, Harta G, Mezey E. Expression of the CB1 and CB2 receptor messenger RNAs during embryonic development in the rat. Neuroscience. 1998;82(4):1131\u201349. https:\/\/doi.org\/10.1016\/s0306-4522(97)00348-5.","journal-title":"Neuroscience."},{"issue":"3","key":"275_CR12","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.0021-8782.2004.00325.x","volume":"205","author":"J Begbie","year":"2004","unstructured":"Begbie J, Doherty P, Graham A. Cannabinoid receptor, CB1, expression follows neuronal differentiation in the early chick embryo. J Anat. 2004;205(3):213\u20138. https:\/\/doi.org\/10.1111\/j.0021-8782.2004.00325.x.","journal-title":"J Anat"},{"issue":"2","key":"275_CR13","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/bdrb.20348","volume":"95","author":"D Psychoyos","year":"2012","unstructured":"Psychoyos D, Vinod KY, Cao J, Hyson RL, Wlodarczyk B, He W, et al. Cannabinoid receptor 1 signaling in embryo neurodevelopment. Birth Defects Res B Dev Reprod Toxicol. 2012;95(2):137\u201350. https:\/\/doi.org\/10.1002\/bdrb.20348.","journal-title":"Birth Defects Res B Dev Reprod Toxicol"},{"issue":"3","key":"275_CR14","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/S0306-4522(03)00020-4","volume":"118","author":"X Wang","year":"2003","unstructured":"Wang X, Dow-Edwards D, Keller E, Hurd YL. Preferential limbic expression of the cannabinoid receptor mRNA in the human fetal brain. Neuroscience. 2003;118(3):681\u201394. https:\/\/doi.org\/10.1016\/S0306-4522(03)00020-4.","journal-title":"Neuroscience."},{"issue":"1","key":"275_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-53579-3","volume":"9","author":"E Innocenzi","year":"2019","unstructured":"\u2022\u2022 Innocenzi E, De Domenico E, Ciccarone F, Zampieri M, Rossi G, Cicconi R, et al. Paternal activation of CB 2 cannabinoid receptor impairs placental and embryonic growth via an epigenetic mechanism. Sci Rep. 2019;9(1):1\u201313. https:\/\/doi.org\/10.1038\/s41598-019-53579-3Demonstrated role of CBR2 agonist in inducing epigenetic alterations in male gametes that are retained in the placenta.","journal-title":"Sci Rep"},{"issue":"2","key":"275_CR16","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1097\/00001756-199302000-00005","volume":"4","author":"F Rodr\u00edguez de Fonseca","year":"1993","unstructured":"Rodr\u00edguez de Fonseca F, Ramos JA, Bonnin A, Fern\u00e1ndez-Ruiz JJ. Presence of cannabinoid binding sites in the brain from early postnatal ages. Neuroreport. 1993;4(2):135\u20138. https:\/\/doi.org\/10.1097\/00001756-199302000-00005.","journal-title":"Neuroreport."},{"issue":"4","key":"275_CR17","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1002\/syn.20844","volume":"65","author":"L Heng","year":"2011","unstructured":"Heng L, Beverley JA, Steiner H, Tseng KY. Differential developmental trajectories for CB1 cannabinoid receptor expression in limbic\/associative and sensorimotor cortical areas. Synapse. 2011;65(4):278\u201386. https:\/\/doi.org\/10.1002\/syn.20844.","journal-title":"Synapse."},{"issue":"9","key":"275_CR18","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.tips.2011.05.004","volume":"32","author":"E Keimpema","year":"2011","unstructured":"Keimpema E, Mackie K, Harkany T. Molecular model of cannabis sensitivity in developing neuronal circuits. Trends Pharmacol Sci. 2011;32(9):551\u201361. https:\/\/doi.org\/10.1016\/j.tips.2011.05.004.","journal-title":"Trends Pharmacol Sci"},{"issue":"3","key":"275_CR19","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1037\/abn0000410","volume":"128","author":"JM Twenge","year":"2019","unstructured":"Twenge JM, Cooper AB, Joiner TE, Duffy ME, Binau SG. Age, period, and cohort trends in mood disorder indicators and suicide-related outcomes in a nationally representative dataset, 2005-2017. J Abnorm Psychol. 2019;128(3):185\u201399. https:\/\/doi.org\/10.1037\/abn0000410.","journal-title":"J Abnorm Psychol"},{"issue":"10","key":"275_CR20","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1111\/j.1460-9568.2011.07884.x","volume":"34","author":"CV Morris","year":"2011","unstructured":"Morris CV, DiNieri JA, Szutorisz H, Hurd YL. Molecular mechanisms of maternal cannabis and cigarette use on human neurodevelopment: prenatal cannabis and cigarette molecular mechanisms. Eur J Neurosci. 2011;34(10):1574\u201383. https:\/\/doi.org\/10.1111\/j.1460-9568.2011.07884.x.","journal-title":"Eur J Neurosci"},{"key":"275_CR21","doi-asserted-by":"publisher","unstructured":"Chadwick B, Miller ML, Hurd YL. Cannabis use during adolescent development: susceptibility to psychiatric illness. Front Psychiatry. 2013;4. https:\/\/doi.org\/10.3389\/fpsyt.2013.00129.","DOI":"10.3389\/fpsyt.2013.00129"},{"issue":"7","key":"275_CR22","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.biopsych.2015.09.014","volume":"79","author":"H Szutorisz","year":"2016","unstructured":"Szutorisz H, Hurd YL. Epigenetic effects of cannabis exposure. Biol Psychiatry. 2016;79(7):586\u201394. https:\/\/doi.org\/10.1016\/j.biopsych.2015.09.014.","journal-title":"Biol Psychiatry"},{"key":"275_CR23","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.ntt.2016.05.005","volume":"58","author":"H Szutorisz","year":"2016","unstructured":"Szutorisz H, Egerv\u00e1ri G, Sperry J, Carter JM, Hurd YL. Cross-generational THC exposure alters the developmental sensitivity of ventral and dorsal striatal gene expression in male and female offspring. Neurotoxicol Teratol. 2016;58:107\u201314. https:\/\/doi.org\/10.1016\/j.ntt.2016.05.005.","journal-title":"Neurotoxicol Teratol"},{"issue":"6","key":"275_CR24","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1038\/npp.2013.352","volume":"39","author":"H Szutorisz","year":"2014","unstructured":"Szutorisz H, DiNieri JA, Sweet E, Egervari G, Michaelides M, Carter JM, et al. Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation. Neuropsychopharmacol. 2014;39(6):1315\u201323. https:\/\/doi.org\/10.1038\/npp.2013.352.","journal-title":"Neuropsychopharmacol."},{"issue":"13","key":"275_CR25","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.1038\/npp.2015.155","volume":"40","author":"CT Watson","year":"2015","unstructured":"Watson CT, Szutorisz H, Garg P, Martin Q, Landry JA, Sharp AJ, et al. Genome-wide DNA methylation profiling reveals epigenetic changes in the rat nucleus accumbens associated with cross-generational effects of adolescent THC exposure. Neuropsychopharmacol. 2015;40(13):2993\u20133005. https:\/\/doi.org\/10.1038\/npp.2015.155.","journal-title":"Neuropsychopharmacol."},{"key":"275_CR26","doi-asserted-by":"publisher","first-page":"106806","DOI":"10.1016\/j.ntt.2019.04.003","volume":"74","author":"ED Levin","year":"2019","unstructured":"Levin ED, Hawkey AB, Hall BJ, Cauley M, Slade S, Yazdani E, et al. Paternal THC exposure in rats causes long-lasting neurobehavioral effects in the offspring. Neurotoxicol Teratol. 2019;74:106806. https:\/\/doi.org\/10.1016\/j.ntt.2019.04.003.","journal-title":"Neurotoxicol Teratol"},{"key":"275_CR27","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.neubiorev.2017.05.011","volume":"85","author":"H Szutorisz","year":"2018","unstructured":"Szutorisz H, Hurd YL. High times for cannabis: epigenetic imprint and its legacy on brain and behavior. Neurosci Biobehav Rev. 2018;85:93\u2013101. https:\/\/doi.org\/10.1016\/j.neubiorev.2017.05.011.","journal-title":"Neurosci Biobehav Rev"},{"issue":"12","key":"275_CR28","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1080\/15592294.2018.1554521","volume":"13","author":"SK Murphy","year":"2018","unstructured":"\u2022\u2022 Murphy SK, Itchon-Ramos N, Visco Z, Huang Z, Grenier C, Schrott R, et al. Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics. 2018;13(12):1208\u201321. https:\/\/doi.org\/10.1080\/15592294.2018.1554521Found correlations between THC exposure levels in human sperm and methylation of 177 genes, as well as substantial overlap in THC target genes in rat sperm and genes reported as having altered methylation in the brains of pre-gestationally exposed rats.","journal-title":"Epigenetics"},{"issue":"11","key":"275_CR29","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1080\/15592294.2019.1633868","volume":"14","author":"AS Reece","year":"2019","unstructured":"Reece AS, Hulse GK. Impacts of cannabinoid epigenetics on human development: reflections on Murphy et. al. \u2018cannabinoid exposure and altered DNA methylation in rat and human sperm\u2019 epigenetics 2018; 13: 1208\u20131221. Epigenetics. 2019;14(11):1041\u201356. https:\/\/doi.org\/10.1080\/15592294.2019.1633868.","journal-title":"Epigenetics."},{"issue":"19","key":"275_CR30","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1161\/CIRCULATIONAHA.110.956839","volume":"123","author":"DE Handy","year":"2011","unstructured":"Handy DE, Castro R, Loscalzo J. Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Circulation. 2011;123(19):2145\u201356. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.110.956839.","journal-title":"Circulation."},{"key":"275_CR31","doi-asserted-by":"publisher","unstructured":"Wen K-X, Mili\u00e7 J, El-Khodor B, Dhana K, Nano J, Pulido T, et al. The role of DNA methylation and histone modifications in neurodegenerative diseases: a systematic review. PLoS One. 2016;11(12). https:\/\/doi.org\/10.1371\/journal.pone.0167201.","DOI":"10.1371\/journal.pone.0167201"},{"key":"275_CR32","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/978-1-4939-3378-5_21","volume-title":"Long Non-Coding RNAs: Methods and Protocols. Methods in Molecular Biology","author":"MD Paraskevopoulou","year":"2016","unstructured":"Paraskevopoulou MD, Hatzigeorgiou AG. Analyzing MiRNA\u2013LncRNA Interactions. In: Feng Y, Zhang L, editors. Long Non-Coding RNAs: Methods and Protocols. Methods in Molecular Biology. New York: Springer; 2016. p. 271\u201386."},{"key":"275_CR33","unstructured":"Reference GH. What are genomic imprinting and uniparental disomy? Genetics Home Reference."},{"issue":"1","key":"275_CR34","doi-asserted-by":"publisher","first-page":"42","DOI":"10.2527\/af.2015-0007","volume":"5","author":"C O'Neill","year":"2015","unstructured":"O'Neill C. The epigenetics of embryo development. Anim Front. 2015;5(1):42\u20139. https:\/\/doi.org\/10.2527\/af.2015-0007.","journal-title":"Anim Front"},{"issue":"6","key":"275_CR35","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.cell.2015.05.039","volume":"161","author":"F von Meyenn","year":"2015","unstructured":"von Meyenn F, Reik W. Forget the parents: epigenetic reprogramming in human germ cells. Cell. 2015;161(6):1248\u201351. https:\/\/doi.org\/10.1016\/j.cell.2015.05.039.","journal-title":"Cell."},{"issue":"11","key":"275_CR36","doi-asserted-by":"publisher","first-page":"e199-e","DOI":"10.1038\/tp.2012.122","volume":"2","author":"KA Gleason","year":"2012","unstructured":"Gleason KA, Birnbaum SG, Shukla A, Ghose S. Susceptibility of the adolescent brain to cannabinoids: long-term hippocampal effects and relevance to schizophrenia. Transl Psychiatry. 2012;2(11):e199-e. https:\/\/doi.org\/10.1038\/tp.2012.122.","journal-title":"Transl Psychiatry"},{"issue":"10","key":"275_CR37","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.biopsych.2012.04.026","volume":"72","author":"HC Tomasiewicz","year":"2012","unstructured":"Tomasiewicz HC, Jacobs MM, Wilkinson MB, Wilson SP, Nestler EJ, Hurd YL. Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability. Biol Psychiatry. 2012;72(10):803\u201310. https:\/\/doi.org\/10.1016\/j.biopsych.2012.04.026.","journal-title":"Biol Psychiatry"},{"key":"275_CR38","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.bbi.2016.02.021","volume":"56","author":"SL Hollins","year":"2016","unstructured":"Hollins SL, Zavitsanou K, Walker FR, Cairns MJ. Alteration of transcriptional networks in the entorhinal cortex after maternal immune activation and adolescent cannabinoid exposure. Brain Behav Immun. 2016;56:187\u201396. https:\/\/doi.org\/10.1016\/j.bbi.2016.02.021.","journal-title":"Brain Behav Immun"},{"issue":"9","key":"275_CR39","doi-asserted-by":"publisher","first-page":"e452-e","DOI":"10.1038\/tp.2014.99","volume":"4","author":"SL Hollins","year":"2014","unstructured":"Hollins SL, Zavitsanou K, Walker FR, Cairns MJ. Alteration of imprinted Dlk1-Dio3 miRNA cluster expression in the entorhinal cortex induced by maternal immune activation and adolescent cannabinoid exposure. Transl Psychiatry. 2014;4(9):e452-e. https:\/\/doi.org\/10.1038\/tp.2014.99.","journal-title":"Transl Psychiatry"},{"issue":"4","key":"275_CR40","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/s41380-018-0243-x","volume":"24","author":"ML Miller","year":"2019","unstructured":"\u2022 Miller ML, Chadwick B, Dickstein DL, Purushothaman I, Egervari G, Rahman T, et al. Adolescent exposure to \u03949-tetrahydrocannabinol alters the transcriptional trajectory and dendritic architecture of prefrontal pyramidal neurons. Mol Psychiatry. 2019;24(4):588\u2013600. https:\/\/doi.org\/10.1038\/s41380-018-0243-xFound differential expression of genes in brain tissue, which were implicated in neurodevelopment and psychiatric disorders, in rat adolescents exposed to THC.","journal-title":"Mol Psychiatry"},{"key":"275_CR41","doi-asserted-by":"publisher","unstructured":"\u2022\u2022 Gerra MC, Jayanthi S, Manfredini M, Walther D, Schroeder J, Phillips KA, et al. Gene variants and educational attainment in cannabis use: mediating role of DNA methylation. Transl Psychiatry. 2018;8. https:\/\/doi.org\/10.1038\/s41398-017-0087-1DNA methylation higher in cannabis users, compared to controls, in exon 8 of DRD2 gene in peripheral whole blood of human subjects, which could underly reward deficit condition.","DOI":"10.1038\/s41398-017-0087-1"},{"issue":"6","key":"275_CR42","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1111\/adb.12446","volume":"22","author":"J Tomas-Roig","year":"2017","unstructured":"\u2022 Tomas-Roig J, Benito E, Agis-Balboa R, Piscitelli F, Hoyer-Fender S, Di Marzo V, et al. Chronic exposure to cannabinoids during adolescence causes long-lasting behavioral deficits in adult mice: Long-lasting WIN55212.2 effect. Addict Biol. 2017;22(6):1778\u201389. https:\/\/doi.org\/10.1111\/adb.12446Mice exposed to CBR1 agonist had hypermethylation of Rgs7 in the hippocampus, compared to controls, which could have implications for memory, motor control, vision, and reward behavior.","journal-title":"Addict Biol"},{"issue":"6","key":"275_CR43","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1097\/AOG.0000000000002619","volume":"131","author":"B Dickson","year":"2018","unstructured":"Dickson B, Mansfield C, Guiahi M, Allshouse AA, Borgelt LM, Sheeder J, et al. Recommendations from cannabis dispensaries about first-trimester Cannabis use. Obstet Gynecol. 2018;131(6):1031\u20138. https:\/\/doi.org\/10.1097\/AOG.0000000000002619.","journal-title":"Obstet Gynecol"},{"issue":"6","key":"275_CR44","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/jp.2013.180","volume":"34","author":"SC Jaques","year":"2014","unstructured":"Jaques SC, Kingsbury A, Henshcke P, Chomchai C, Clews S, Falconer J, et al. Cannabis, the pregnant woman and her child: weeding out the myths. J Perinatol. 2014;34(6):417\u201324. https:\/\/doi.org\/10.1038\/jp.2013.180.","journal-title":"J Perinatol"},{"issue":"3","key":"275_CR45","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S0892-0362(00)00066-0","volume":"22","author":"L Goldschmidt","year":"2000","unstructured":"Goldschmidt L, Day NL, Richardson GA. Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicol Teratol. 2000;22(3):325\u201336. https:\/\/doi.org\/10.1016\/S0892-0362(00)00066-0.","journal-title":"Neurotoxicol Teratol"},{"issue":"1","key":"275_CR46","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.ntt.2011.08.009","volume":"34","author":"L Goldschmidt","year":"2012","unstructured":"Goldschmidt L, Richardson GA, Willford JA, Severtson SG, Day NL. School achievement in 14-year-old youths prenatally exposed to marijuana. Neurotoxicol Teratol. 2012;34(1):161\u20137. https:\/\/doi.org\/10.1016\/j.ntt.2011.08.009.","journal-title":"Neurotoxicol Teratol"},{"issue":"3","key":"275_CR47","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.ntt.2005.02.001","volume":"27","author":"JS Noland","year":"2005","unstructured":"Noland JS, Singer LT, Short EJ, Minnes S, Arendt RE, Lester Kirchner H, et al. Prenatal drug exposure and selective attention in preschoolers. Neurotoxicol Teratol. 2005;27(3):429\u201338. https:\/\/doi.org\/10.1016\/j.ntt.2005.02.001.","journal-title":"Neurotoxicol Teratol"},{"issue":"2","key":"275_CR48","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1097\/01.chi.0000184930.18552.4d","volume":"45","author":"SL Leech","year":"2006","unstructured":"Leech SL, Larkby CA, Day R, Day NL. Predictors and correlates of high levels of depression and anxiety symptoms among children at age 10. J Am Acad Child Adolesc Psychiatry. 2006;45(2):223\u201330. https:\/\/doi.org\/10.1097\/01.chi.0000184930.18552.4d.","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"4","key":"275_CR49","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1097\/AOG.0000000000001649","volume":"128","author":"SN Conner","year":"2016","unstructured":"Conner SN, Bedell V, Lipsey K, Macones GA, Cahill AG, Tuuli MG. Maternal marijuana use and adverse neonatal outcomes: a systematic review and meta-analysis. Obstet Gynecol. 2016;128(4):713\u201323. https:\/\/doi.org\/10.1097\/AOG.0000000000001649.","journal-title":"Obstet Gynecol"},{"key":"275_CR50","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.reprotox.2016.04.021","volume":"62","author":"SY Leemaqz","year":"2016","unstructured":"Leemaqz SY, Dekker GA, McCowan LM, Kenny LC, Myers JE, Simpson NAB, et al. Maternal marijuana use has independent effects on risk for spontaneous preterm birth but not other common late pregnancy complications. Reprod Toxicol. 2016;62:77\u201386. https:\/\/doi.org\/10.1016\/j.reprotox.2016.04.021.","journal-title":"Reprod Toxicol"},{"issue":"1","key":"275_CR51","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/mp.2016.17","volume":"22","author":"GA Vargish","year":"2017","unstructured":"Vargish GA, Pelkey KA, Yuan X, Chittajallu R, Collins D, Fang C, et al. Persistent inhibitory circuit defects and disrupted social behaviour following in utero exogenous cannabinoid exposure. Mol Psychiatry. 2017;22(1):56\u201367. https:\/\/doi.org\/10.1038\/mp.2016.17.","journal-title":"Mol Psychiatry"},{"key":"275_CR52","doi-asserted-by":"publisher","unstructured":"Ryan SA, Ammerman SD, O\u2019Connor ME. Prevention CoSUA, Breastfeeding SO. Marijuana use during pregnancy and breastfeeding: implications for neonatal and childhood outcomes. Pediatrics. 2018;142(3). https:\/\/doi.org\/10.1542\/peds.2018-1889.","DOI":"10.1542\/peds.2018-1889"},{"issue":"12","key":"275_CR53","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1097\/CHI.0b013e3181bfa8ee","volume":"48","author":"H El Marroun","year":"2009","unstructured":"El Marroun H, Tiemeier H, Steegers EAP, Jaddoe VWV, Hofman A, Verhulst FC, et al. Intrauterine Cannabis exposure affects fetal growth trajectories: the generation R study. J Am Acad Child Adolesc Psychiatry. 2009;48(12):1173\u201381. https:\/\/doi.org\/10.1097\/CHI.0b013e3181bfa8ee.","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"9","key":"275_CR54","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1373\/clinchem.2010.147876","volume":"56","author":"TR Gray","year":"2010","unstructured":"Gray TR, Eiden RD, Leonard KE, Connors GJ, Shisler S, Huestis MA. Identifying prenatal Cannabis exposure and effects of concurrent tobacco exposure on neonatal growth. Clin Chem. 2010;56(9):1442\u201350. https:\/\/doi.org\/10.1373\/clinchem.2010.147876.","journal-title":"Clin Chem"},{"issue":"8","key":"275_CR55","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.biopsych.2011.06.027","volume":"70","author":"JA DiNieri","year":"2011","unstructured":"DiNieri JA, Wang X, Szutorisz H, Spano SM, Kaur J, Casaccia P, et al. Maternal Cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry. 2011;70(8):763\u20139. https:\/\/doi.org\/10.1016\/j.biopsych.2011.06.027.","journal-title":"Biol Psychiatry"},{"issue":"1","key":"275_CR56","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0149-7634(99)00065-2","volume":"24","author":"DS Zahm","year":"2000","unstructured":"Zahm DS. An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbens. Neurosci Biobehav Rev. 2000;24(1):85\u2013105. https:\/\/doi.org\/10.1016\/S0149-7634(99)00065-2.","journal-title":"Neurosci Biobehav Rev"},{"issue":"22","key":"275_CR57","doi-asserted-by":"publisher","first-page":"35933","DOI":"10.18632\/oncotarget.16411","volume":"8","author":"Z Zhu","year":"2017","unstructured":"Zhu Z, Wang G, Ma K, Cui S, Wang J-H. GABAergic neurons in nucleus accumbens are correlated to resilience and vulnerability to chronic stress for major depression. Oncotarget. 2017;8(22):35933\u201345. https:\/\/doi.org\/10.18632\/oncotarget.16411.","journal-title":"Oncotarget"},{"issue":"12","key":"275_CR58","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1016\/j.biopsych.2004.10.015","volume":"56","author":"X Wang","year":"2004","unstructured":"Wang X, Dow-Edwards D, Anderson V, Minkoff H, Hurd YL. In utero marijuana exposure associated with abnormal amygdala dopamine D2 gene expression in the human fetus. Biol Psychiatry. 2004;56(12):909\u201315. https:\/\/doi.org\/10.1016\/j.biopsych.2004.10.015.","journal-title":"Biol Psychiatry"},{"issue":"4","key":"275_CR59","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/sj.tpj.6500375","volume":"6","author":"X Wang","year":"2006","unstructured":"Wang X, Dow-Edwards D, Anderson V, Minkoff H, Hurd YL. Discrete opioid gene expression impairment in the human fetal brain associated with maternal marijuana use. Pharmacogenomics J. 2006;6(4):255\u201364. https:\/\/doi.org\/10.1038\/sj.tpj.6500375.","journal-title":"Pharmacogenomics J"},{"issue":"1","key":"275_CR60","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/npp.2014.147","volume":"40","author":"EJ Ross","year":"2015","unstructured":"Ross EJ, Graham DL, Money KM, Stanwood GD. Developmental consequences of fetal exposure to drugs: what we know and what we still must learn. Neuropsychopharmacol. 2015;40(1):61\u201387. https:\/\/doi.org\/10.1038\/npp.2014.147.","journal-title":"Neuropsychopharmacol."},{"issue":"4","key":"275_CR61","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.biopsych.2006.03.073","volume":"61","author":"MS Spano","year":"2007","unstructured":"Spano MS, Ellgren M, Wang X, Hurd YL. Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood. Biol Psychiatry. 2007;61(4):554\u201363. https:\/\/doi.org\/10.1016\/j.biopsych.2006.03.073.","journal-title":"Biol Psychiatry"},{"issue":"6","key":"275_CR62","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1080\/00952990.2017.1314488","volume":"43","author":"PD Fransquet","year":"2017","unstructured":"\u2022 Fransquet PD, Hutchinson D, Olsson CA, Allsop S, Elliott EJ, Burns L, et al. Cannabis use by women during pregnancy does not influence infant DNA methylation of the dopamine receptor DRD4. Am J Drug Alcohol Abuse. 2017;43(6):671\u20137. https:\/\/doi.org\/10.1080\/00952990.2017.1314488DNA methylation of DRD4 was not influenced by human gestational cannabis use, but null findings could be due to use of buccal cells and not neuronal cells.","journal-title":"Am J Drug Alcohol Abuse"},{"issue":"6","key":"275_CR63","doi-asserted-by":"publisher","first-page":"516","DOI":"10.4161\/epi.5.6.12226","volume":"5","author":"CCY Wong","year":"2010","unstructured":"Wong CCY, Caspi A, Williams B, Craig IW, Houts R, Ambler A, et al. A longitudinal study of epigenetic variation in twins. Epigenetics. 2010;5(6):516\u201326. https:\/\/doi.org\/10.4161\/epi.5.6.12226.","journal-title":"Epigenetics."},{"issue":"1","key":"275_CR64","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1111\/ajad.12320","volume":"25","author":"TT Mallard","year":"2016","unstructured":"Mallard TT, Doorley J, Esposito-Smythers CL, McGeary JE. Dopamine D4 receptor VNTR polymorphism associated with greater risk for substance abuse among adolescents with disruptive behavior disorders: preliminary results. Am J Addict. 2016;25(1):56\u201361. https:\/\/doi.org\/10.1111\/ajad.12320.","journal-title":"Am J Addict"},{"key":"275_CR65","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.ijdevneu.2018.11.007","volume":"72","author":"Z Ibn Lahmar Andaloussi","year":"2019","unstructured":"\u2022 Ibn Lahmar Andaloussi Z, Taghzouti K, Abboussi O. Behavioural and epigenetic effects of paternal exposure to cannabinoids during adolescence on offspring vulnerability to stress. Int J Dev Neurosci. 2019;72:48\u201354. https:\/\/doi.org\/10.1016\/j.ijdevneu.2018.11.007Pre-gestational exposure to cannbinoids during adolescence can promote stress-induced anxiety and alter the epigenetic programming of offspring in rats.","journal-title":"Int J Dev Neurosci"},{"issue":"4","key":"275_CR66","doi-asserted-by":"publisher","first-page":"462","DOI":"10.18632\/oncotarget.497","volume":"3","author":"D Jjingo","year":"2012","unstructured":"Jjingo D, Conley AB, Yi SV, Lunyak VV, Jordan IK. On the presence and role of human gene-body DNA methylation. Oncotarget. 2012;3(4):462\u201374. https:\/\/doi.org\/10.18632\/oncotarget.497.","journal-title":"Oncotarget"},{"key":"275_CR67","unstructured":"GeneCards - Human Genes | Gene Database | Gene Search."},{"issue":"11","key":"275_CR68","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1177\/0269881113503504","volume":"27","author":"FM Vassoler","year":"2013","unstructured":"Vassoler FM, Johnson NL, Byrnes EM. Female adolescent exposure to cannabinoids causes transgenerational effects on morphine sensitization in female offspring in the absence of in utero exposure. J Psychopharmacol. 2013;27(11):1015\u201322. https:\/\/doi.org\/10.1177\/0269881113503504.","journal-title":"J Psychopharmacol"},{"key":"275_CR69","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13041-017-0324-9","volume":"10","author":"AH Rasmussen","year":"2017","unstructured":"Rasmussen AH, Rasmussen HB, Silahtaroglu A. The DLGAP family: neuronal expression, function and role in brain disorders. Mol Brain. 2017;10:43. https:\/\/doi.org\/10.1186\/s13041-017-0324-9.","journal-title":"Mol Brain"},{"key":"275_CR70","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/2040-2392-4-26","volume":"4","author":"W-H Chien","year":"2013","unstructured":"Chien W-H, Gau SS-F, Liao H-M, Chiu Y-N, Wu Y-Y, Huang Y-S, et al. Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders. Mol Autism. 2013;4:26. https:\/\/doi.org\/10.1186\/2040-2392-4-26.","journal-title":"Mol Autism"},{"issue":"4","key":"275_CR71","doi-asserted-by":"publisher","first-page":"170066","DOI":"10.1503\/jpn.170066","volume":"43","author":"J Soler","year":"2018","unstructured":"Soler J, Fa\u00f1an\u00e1s L, Parellada M, Krebs M-O, Rouleau GA, Fatj\u00f3-Vilas M. Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review. J Psychiatry Neurosci. 2018;43(4):170066\u2013244. https:\/\/doi.org\/10.1503\/jpn.170066.","journal-title":"J Psychiatry Neurosci"},{"issue":"0","key":"275_CR72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15592294.2019.1656158","volume":"0","author":"R Schrott","year":"2019","unstructured":"\u2022\u2022 Schrott R, Acharya K, Itchon-Ramos N, Hawkey AB, Pippen E, Mitchell JT, et al. Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm. Epigenetics. 2019;0(0):1\u201313. https:\/\/doi.org\/10.1080\/15592294.2019.1656158Identified region of Dlgap2, which is strongly implicated in the development of autism, with differential methylation in eight CpG sites in THC exposed rat sperm, which was consistent in human sperm.","journal-title":"Epigenetics"},{"issue":"6","key":"275_CR73","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/j.cell.2015.04.053","volume":"161","author":"WC Tang Walfred","year":"2015","unstructured":"Tang Walfred WC, Dietmann S, Irie N, Leitch Harry G, Floros Vasileios I, Bradshaw Charles R, et al. A unique gene regulatory network resets the human germline epigenome for development. Cell. 2015;161(6):1453\u201367. https:\/\/doi.org\/10.1016\/j.cell.2015.04.053.","journal-title":"Cell."},{"key":"275_CR74","unstructured":"Lipari RN. Key Substance Use and Mental Health Indicators in the United States: Results from the 2018 National Survey on Drug Use and Health. 2018:82."},{"issue":"7","key":"275_CR75","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/j.biopsych.2016.01.004","volume":"79","author":"MA ElSohly","year":"2016","unstructured":"ElSohly MA, Mehmedic Z, Foster S, Gon C, Chandra S, Church JC. Changes in Cannabis potency over the last 2 decades (1995\u20132014): analysis of current data in the United States. Biol Psychiatry. 2016;79(7):613\u20139. https:\/\/doi.org\/10.1016\/j.biopsych.2016.01.004.","journal-title":"Biol Psychiatry"},{"key":"275_CR76","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.pharmthera.2017.08.014","volume":"182","author":"KS Grant","year":"2018","unstructured":"Grant KS, Petroff R, Isoherranen N, Stella N, Burbacher TM. Cannabis use during pregnancy: pharmacokinetics and effects on child development. Pharmacol Ther. 2018;182:133\u201351. https:\/\/doi.org\/10.1016\/j.pharmthera.2017.08.014.","journal-title":"Pharmacol Ther"},{"issue":"1","key":"275_CR77","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-23612-y","volume":"8","author":"MB Maamar","year":"2018","unstructured":"Maamar MB, Sadler-Riggleman I, Beck D, Skinner MK. Epigenetic Transgenerational inheritance of altered sperm histone retention sites. Sci Rep. 2018;8(1):1\u201310. https:\/\/doi.org\/10.1038\/s41598-018-23612-y.","journal-title":"Sci Rep"}],"container-title":["Current Environmental Health Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40572-020-00275-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40572-020-00275-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40572-020-00275-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T23:37:12Z","timestamp":1621640232000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40572-020-00275-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,22]]},"references-count":77,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["275"],"URL":"https:\/\/doi.org\/10.1007\/s40572-020-00275-4","relation":{},"ISSN":["2196-5412"],"issn-type":[{"value":"2196-5412","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,22]]},"assertion":[{"value":"22 May 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"AS and AC report grants and non-financial support from Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental Protection Agency, during the conduct of the study. MS and FK report no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights and Informed Consent"}}]}}