Canabis in the Development and Homeostasis of the Nerve System

Authors: J. Blahoš Jr 1,2
Authors‘ workplace: Oddělení molekulární farmakologie, Ústav molekulární genetiky AV ČR v. v. i. 1;  Farmakologický ústav 2. LF UK v Praze 2
Published in: Cesk Slov Neurol N 2013; 76/109(5): 559-564
Category: Review Article

Vzniklo za podpory Grantové agentury Akademie věd GAAV500390701.
Marihuana je jednou z nejčastěji požívaných ilegálních drog mezi dospívající mládeží a mladými dospělými. Tím koliduje expozice psychoaktivních látek z konopí, především pak delta 9- tetrahydrokanabinolu (THC), s kritickými vývojovými stadii mozku. U matek‑ dosavadních kuřaček marihuany může docházet k ovlivnění plodu THC i po zahájení abstinence v rámci rozpoznání těhotenství, neboť lipofilní THC akumuluje v tukové tkáni a je uvolňován při jejím odbourávání.


Marihuana is one of the most frequently abused illicit drugs among adolescents and young adults. As such, exposure to psychoactive ingredients, with delta 9-tetrahydrocanabinol (THC) being the most prevalent, collide with critical periods of brain development. Firstly, in mothers who cease to abuse cannabis at the onset of pregnancy, THC and other lipid-soluble substances might still circulate in their blood at levels that may interfere with the brain development of the fetus. This is due to the chemical nature of THC and related substances; these are lipophilic and accumulate in the body fat. During pregnancy, the fat redistribution leads to release of cannabinoids into the blood stream. These substances readily cross placental barrier and enter fetal circulation. The second period of brain maturation that is influenced by THC exposure in many smokers is during puberty and is associated with an increased risk of neuropsychiatric consequences. The third negative aspect of cannabis abuse giving rise to neurodevelopmental disturbances is related to the „quality“ of the newly developed species of the cannabis sativa plant with as much as 25 times higher concentration of THC than in the samples obtained a decade ago, not mentioning the availability of new synthetic cannabinoid-like ligands of obscure, usually Chinese origin. Legalization of cannabis may be beneficial in certain medical indications but, on the other hand, it might bring false anticipation of harmlessness. The purpose of this review article is to discuss potential side effects of marihuana use during periods of nervous system development both in utero and in adolescence.

Key words:
endocannabinoid – cannabis – pregnancy

The author declare he has no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.


1. Kano M, Ohno‑ Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid‑ mediated control of synaptic transmission. Physiol Rev 2009; 89(1): 309– 380.

2. Mackie K. Cannabinoid receptors: where they are and what they do. J Neuroendocrinol 2008; 20 (Suppl 1):10– 14.

3. Gómez‑ Ruiz M, Hernández M, de Miguel R, Ramos JA. An overview on the bio­chemistry of the cannabinoid system. Mol Neurobio­l 2007; 36(1): 3– 14.

4. Mackie K. Signaling via CNS cannabinoid receptors. Mol Cell Endocrinol 2008; 286 (1– 2 Suppl 1): S60– S65.

5. Mackie K. Cannabinoid receptor homo‑  and heterodimerization. Life Sci 2005; 77(14): 1667– 1673.

6. Mikasova L, Groc L, Choquet D, Manzoni OJ. Altered surface trafficking of presynaptic cannabinoid type 1 receptor in and out synaptic terminals parallels receptor desensitization. Proc Natl Acad Sci U S A 2008; 105(47): 18596– 18601.

7. Keimpema E, Mackie K, Harkany T. Molecular model of cannabis sensitivity in developing neuronal circuits. Trends Pharmacol Sci 2011; 32(9): 551– 561.

8. Fernández‑ Ruiz J, Berrendero F, Hernández ML, Ramos JA. The endogenous cannabinoid system and brain development. Trends Neurosci 2000; 23(1): 14– 20.

9. Harkany T, Mackie K, Doherty P. Wiring and firing neuronal networks: endocannabinoids take center stage. Curr Opin Neurobio­l 2008; 18(3): 338– 345.

10. Morris CV, DiNieri JA, Szutorisz H, Hurd YL. Molecular mechanisms of maternal cannabis and cigarette use on human neurodevelopment. Eur J Neurosci 2011; 34(10): 1574– 1583.

11. Glass M, Dragunow M, Faull RL. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 1997; 77(2): 299– 318.

12. Psychoyos D, Vinod KY, Cao J, Xie S, Hyson RL, Wlodarczyk B et al. Cannabinoid Receptor 1 Signaling in Embryo Neurodevelopment. Birth Defects Res B Dev Reprod Toxicol 2012; 95(2): 137– 150.

13. Day NL, Leech SL, Goldschmidt L. The effects of prenatal marijuana exposure on delinquent behaviors are mediated by measures of neurocognitive functioning. Neurotoxicol Teratol 2011; 33(1): 129– 136.

14. Fried PA, Watkinson B, Gray R. Differential effects on cognitive functioning in 13-  to 16‑year‑ olds prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol 2003; 25(4): 427– 436.

15. Goldschmidt L, Richardson GA, Willford J, Day NL. Prenatal marijuana exposure and intelligence test performance at age 6. J Am Acad Child Adolesc Psychiatry 2008; 47(3): 254– 263.

16. McGrath J, Welham J, Scott J, Varghese D, Degenhardt L, Hayatbakhsh MR et al. Association between cannabis use and psychosis‑related outcomes using sibling pair analysis in a cohort of young adults. Arch Gen Psychiatry 2010; 67(5): 440– 447.

17. Fergusson DM, Horwood LJ, Swain‑Campbell NR. Cannabis dependence and psychotic symptoms in young people. Psychol Med 2003; 33(1): 15– 21.

18. Mackie K. Understanding cannabinoid psychoactivity with mouse genetic models. PLoS Biol 2007; 5(10): e280.

19. Fried PA, Watkinson B, Gray R. Neurocognitive consequences of marihuana – a comparison with pre‑drug performance. Neurotoxicol Teratol 2005; 27(2): 231– 239.

20. El Marroun H, Tiemeier H, Jaddoe VW, Hofman A, Mackenbach JP, Steegers EA et al. Demographic, emotional and social determinants of cannabis use in early pregnancy: the Generation R study. Drug Alcohol Depend 2008; 98(3): 218– 226.

21. Gray KA, Day NL, Leech S, Richardson GA. Prenatal marijuana exposure: effect on child depressive symptoms at ten years of age. Neurotoxicol Teratol 2005; 27(3): 439– 448.

22. Arseneault L, Cannon M, Poulton R, Murray R, Caspi A, Moffitt TE. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 2002; 325(7374): 1212– 1213.

23. Dinieri JA, Hurd YL. Rat models of prenatal and adolescent cannabis exposure. Methods Mol Biol 2012; 829: 231– 242.

24. Trezza V, Campolongo P, Manduca A, Morena M, Palmery M, Vanderschuren LJ et al. Altering endocan­nabinoid neurotransmission at critical developmental ages: impact on rodent emotionality and cognitive performance. Front Behav Neurosci 2012; 6: 2.

25. Day NL, Goldschmidt L, Thomas CA. Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14. Addiction 2006; 101(9): 1313– 1322.

Paediatric neurology Neurosurgery Neurology

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Czech and Slovak Neurology and Neurosurgery

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