Cannabis sativa neurotoxicity and impacts on the brain tissue morphology

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Bárbara da Silva Santos
Marcelo Coertjens

Abstract

In order to understand psychological and behavioral impact among Cannabis sativa users, experiments have been developed by analyzing the relationship between the intensity of the use with injury and inflammation biomarkers. Therefore, this paper aimed to carry out a literature review, relating biochemical markers of neurotoxicity and their impact on morphology of brain tissue in Cannabis sativa users, during the exposure to Δ9-THC intravenously and in in vitro studies. This is a narrative review whose bibliographic research was managed in PubMed, SciELO and Google Scholar databases, using the following terms as inclusion criterion: “Cannabis sativa”, “marijuana”, “maconha”, “Δ9-THC”, “neurotrophins”, “neurotrofinas”, “prostaglandins”, “prostaglandinas”, “BDNF” and “NGF”. Thereby, 40 articles were selected to integrate the present review, dated from 1987 to 2013. The period of this literature review was from August 2011 to May 2013. It was possible to identify the types and the magnitude of morphological and biochemical changes resulting from the Cannabis sativa use or exposure to Δ9-THC. In general, a reduction was found in gray and white brain mass, in density of hippocampus, in the volume of nerve cells, among others. We also observed changes in serum levels of neurotrophins and in prostaglandin biosynthesis, in accordance with methodology used or the evaluated area. These findings could be related to behavioral changes observed in Cannabis sativa users, clarifying, for instance, many psychological symptoms reported in literature.

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How to Cite
Santos, B. da S., & Coertjens, M. (2014). Cannabis sativa neurotoxicity and impacts on the brain tissue morphology. ABCS Health Sciences, 39(1). https://doi.org/10.7322/abcshs.v39i1.250
Section
Review Articles

References

1. United Nations Office for Drug Control and Crime Prevention. World drug report. Geneva: United Nations Publications; 2013.

2. Crippa JA, Lacerda ALT, Amaro E, Filho GB, Zuardi AW, Bressan RA. Efeitos cerebrais da maconha: resultados dos estudos de neuroimagem. Rev Bras Psiquiatr. 2005;27(1):70-8. http://dx.doi.org/10.1590/S1516-44462005000100016


3. Chan GCK, Hinds TR, Impey S, Storm DR. Hippocampal neurotoxicity of ∆9-tetrahydrocannabinol. J Neurosci. 1998;18(14):5322-32.

4. Lawston J, Borella A, Robinson JK, Whitaker-Azmitia PM. Changes in hippocampal morphology following chronic treatment with the synthetic cannabinoid WIN 55,212-2. Brain Res. 2000;877(2):407-10. http://dx.doi.org/10.1016/S0006-8993(00)02739-6

5. Schlaepfer TE, Lancaster E, Heidbreder R, Strain EC, Kosel M, Fisch HU, et al. Decreased frontal white-matter volume in chronic substance abuse. Int J Neuropsychopharmacol. 2006;9(2):147-53. http://dx.doi.org/10.1017/S1461145705005705

6. Yücel M, Solowij N, Respondek C, Whittle S, Fornito A, Pantelis C, et al. Regional brain abnormalities associated with long-term heavy Cannabis use. Arch Gen Psychiatry. 2008;65(6):694-701. http://dx.doi.org/10.1001/archpsyc.65.6.694

7. Shimizu E, Hashimoto K, Watanabe H, Komatsu N, Okamura N, Koike K, et al. Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenia are indistinguishable from controls. Neurosci Lett. 2003;351(2):111-14. http://dx.doi.org/10.1016/j.neulet.2003.08.004

8. D'Souza DC, Pittman B, Perry E, Simen A. Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans. Psychopharmacology. 2009;202(4):569-78. http://dx.doi.org/10.1007/s00213-008-1333-2

9. Tuszynski MH, Blesch A. Nerve growth factor: from animal models of cholinergic neuronal degeneration to gene therapy in Alzheimer's disease. Prog Brain Res. 2004;146:441-9. http://dx.doi.org/10.1016/S0079-6123(03)46028-7

10. Kozak KR, Crews BC, Morrow JD, Wang LH, Ma YH, Weinander R, et al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem. 2002;277(47):44877-85. http://dx.doi.org/10.1074/jbc.M206788200

11. Veldhuis WB, van der Stelt M, Wadman MW, van Zadelhoff G, Maccarrone M, Fezza F, et al. V. Neuroprotection by the endogenous cannabinoid anandamide and arvanil against in vivo excitotoxicity in the rat: role of vanilloid receptors and lipoxygenases. J Neurosci. 2003;23(10):4127-33.

12. Wilson W, Mathew R, Turkington T, Hawk T, Coleman RE, Provenzale J. Brain morphological changes and early marijuana use: a magnetic resonance and positron emission tomography study. J Addict Dis. 2000;19(1):1-22. http://dx.doi.org/10.1300/J069v19n01_01

13. Matochik JA, Eldreth DA, Cadet JL, Bolla KI. Altered brain tissue composition in heavy marijuana users. Drug Alcohol Depend. 2005;77(1):23-30. http://dx.doi.org/10.1016/j.drugalcdep.2004.06.011

14. Block RI, O'Leary DS, Ehrhardt JC, Augustinack JC, Ghoneim MM, Arndt S, et al. Effects of frequent marijuana use on brain tissue volume and composition. Neuroreport. 2000;11(3):491-6. http://dx.doi.org/10.1097/00001756-200002280-00013

15. Scallet AC, Uemura E, Andrews A, Ali SF, McMillan DE, Paule MG, et al. Morphometric studies of the rat hippocampus following chronic delta-9-tetrahydrocannabinol (THC). Brain Res.1987;436(1):193-8. http://dx.doi.org/10.1016/0006-8993(87)91576-9

16. Landfield PW, Cadwallader LB, Vinsant S. Quantitative changes in hippocampal structure following long-term exposure to ∆9-tetrahydrocannabinol: possible mediation by glucocorticoid systems. Brain Res. 1988;443(1-2):47-62. http://dx.doi.org/10.1016/0006-8993(88)91597-1

17. Allen SJ, Dawbarn D. Clinical relevance of the neurotrophins and their receptors. Clin Sci. 2006;110(2):175-91. http://dx.doi.org/10.1042/CS20050161

18. Madduri S, Papaloïzos M, Gander B. Synergistic effect of GDNF and NGF on axonal branching and elongation in vitro. Neurosci Res. 2009;65(1): 88-97. http://dx.doi.org/10.1016/j.neures.2009.06.003

19. Schmidt HD, Duman RS. Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models. Neuropsychopharmacol. 2010;35(12):2378-91. http://dx.doi.org/10.1038/npp.2010.114

20. Angelucci F, Ricci V, Spalletta G, Pomponi M, Tonioni F, Caltagirone C, et al. Reduced serum concentrations of nerve growth factor, but not brain-derived neurotrophic factor, in chronic cannabis abusers. Eur Neuropsychopharmacol. 2008;18(12):882-7. http://dx.doi.org/10.1016/j.euroneuro.2008.07.008

21. Jockers-Scherübl MC, Matthies U, Danker-Hopfe H, Lang UE, Mahlberg R, Hellweg R. Chronic cannabis abuse raises nerve growth factor serum concentrations in drug-naive schizophrenic patients. J Psychopharmacol. 2003;17(4):439-45. http://dx.doi.org/10.1177/0269881103174007

22. Toyooka K, Asama K, Watanabe Y, Muratake T, Takahashi M, Someya T, et al. Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients. Psychiatry Res. 2002;110(3):249-57. http://dx.doi.org/10.1016/S0165-1781(02)00127-0

23. Yamamoto H, Gurney ME. Human platelets contain brain-derived neurotrophic factor. J Neurosci. 1990;10(11):3469-78.

24. Jockers-Scherübl MC, Danker-Hopfe H, Mahlberg R, Selig F, Rentzsch J, Schurer F, et al. Brain-derived neurotrophic factor serum concentrations are increased in drug-naive schizophrenic patients with chronic Cannabis abuse and multiple substance abuse. Neurosci Lett. 2004;371(1):79-83. http://dx.doi.org/10.1016/j.neulet.2004.08.045

25. Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362(25):2389-98. http://dx.doi.org/10.1056/NEJMcp1000274

26. Jockers-Scherübl MC, Zouboulis CC, Boegner F, Hellweg R. Is nerve growth factor a serum marker for neurological and psychiatric complications in Behçet's disease? Lancet. 1996;347(9006):982. http://dx.doi.org/10.1016/S0140-6736(96)91476-2

27. Wu VW, Mo Q, Yabe T, Schwartz JP, Robinson SE. Perinatal opioids reduce striatal nerve growth factor content in rat striatum. Eur J Pharmacol. 2001;414(2-3):211-4. http://dx.doi.org/10.1016/S0014-2999(01)00807-X

28. Aloe L, Tuveri MA, Guerra G, Pinna L, Tirassa P, Micera A, et al. Changes in human plasma nerve growth factor level after chronic alcohol consumption and withdrawal. Alcohol Clin Exp Res. 1996;20(3):462-5. http://dx.doi.org/10.1111/j.1530-0277.1996.tb01076.x

29. Zhang XY, Xiu MH, Chen C, Yang FD, Wu GY, Lu L, et al. Nicotine dependence and serum BDNF levels in male patients with schizophrenia. Psychopharmacology. 2010;212(3):301-7. http://dx.doi.org/10.1007/s00213-010-1956-y

30. McCarthy DM, Zhang X, Darnell SB, Sangrey GR, Yanagawa Y, Sadri-Vakili G, et al. Cocaine alters BDNF expression and neuronal migration in the embryonic mouse forebrain. J Neurosci. 2011;31(38):13400-11. http://dx.doi.org/10.1523/JNEUROSCI.2944-11.2011

31. Anggadiredja K, Yamaguchi T, Tanaka H, Shoyama Y, Watanabe S, Yamamoto T. Decrease in prostaglandin level is a prerequisite for the expression of cannabinoid withdrawal: a quasi abstinence approach. Brain Res. 2005;1066(1-2):201-5. http://dx.doi.org/10.1016/j.brainres.2005.10.065

32. Sang N, Zhang J, Chen C. COX-2 oxidative metabolite of endocannabinoid 2-AG enhances excitatory glutamatergic synaptic transmission and induces neurotoxicity. J Neurochem. 2007;102(6):1966-77. http://dx.doi.org/10.1111/j.1471-4159.2007.04668.x

33. Păunescu H, Coman OA, Coman L, Ghiţă I, Georgescu SR, Drăghia F, et al. Cannabinoid system and cyclooxygenases inhibitors. J Med Life. 2011;4(1):11-20.

34. Mitchell MD, Sato TA, Wang A, Keelan JA, Ponnampalam AP, Glass M. Cannabinoids stimulate prostaglandin production by human gestational tissues through a tissue and CB1 receptor specific mechanism. Am J Physiol Endocrinol Metab. 2008;294(2):E352-6. http://dx.doi.org/10.1152/ajpendo.00495.2007

35. Ruhaak LR, Felth J, Karlsson PC, Rafter JJ, Verpoorte R, Bohlin L. Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull. 2011;34(5):774-8. http://dx.doi.org/10.1248/bpb.34.774

36. Qamri Z, Preet A, Nasser MW, Bass CE, Leone G, Barsky SH, et al. Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol Cancer Ther. 2009;8(11):3117-29. http://dx.doi.org/10.1158/1535-7163.MCT-09-0448

37. Guindon J, Hohmann AG. The endocannabinoid system and cancer: therapeutic implication. Br J Pharmacol. 2011;163(7):1447-63. http://dx.doi.org/10.1111/j.1476-5381.2011.01327.x

38. Romero TR, Resende LC, Duarte ID. The neuronal NO synthase participation in the peripheral antinociception mechanism induced by several analgesic drugs. 2001. Nitric Oxide. 2011;25(4):431-5. http://dx.doi.org/10.1016/j.niox.2011.08.002

39. Zalesky A, Solowij N, Yücel M, Lubman DI, Takagi M, Harding IH, et al. Effect of long-term cannabis use on axonal fibre connectivity. Brain. 2012;135(Pt 7):2245-55. http://dx.doi.org/10.1093/brain/aws136

40. Batalla A, Bhattacharyya S, Yücel M, Fusar-Poli P, Crippa JA, Nogué S, et al. Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings. PLoS One. 2013;8(2):e55821.