EFEITO DO ESTRESSE NA INFÂNCIA SOBRE COMPORTAMENTOS DEPRESSIVOS NA VIDA ADULTA: POTENCIAL ESTRATÉGIA TERAPÊUTICA DO ÓLEO DE CANNABIS SATIVA DE ESPECTRO COMPLETO
DOI:
https://doi.org/10.58731/2965-0771.2025.104Abstract
Major Depressive Disorder (MDD) is a multifactorial psychiatric condition in which factors such as chronic stress and traumatic events lead to neural and systemic dysfunctions. Evidence indicates that early-life adversities, including maternal deprivation (MD), impair brain development and, when combined with social isolation (SI) in adulthood, increase vulnerability to depressive symptoms and resistance to conventional treatment. The limitations of current therapies drive the investigation of new approaches, including plant-based compounds with potential antidepressant effects. This study evaluated depressive-like behavior and modulation by the endocannabinoid system in rats subjected to stress induced by MD in the early days of life, followed by SI in adulthood, as well as the therapeutic effect of treatment with full-spectrum Cannabis sativa oil. Male Wistar rats were divided into four experimental groups (N=10 per group): non-stressed control + saline; MD+SI + saline; MD+SI + Escitalopram; and MD+SI + C. sativa full-spectrum oil. The stress protocol was followed by chronic treatment for 14 days and subsequent behavioral assessment through locomotor activity and forced swim tests. The results demonstrated that the MD+SI + saline group exhibited a significant increase in immobility time in the forced swim test compared to the control group, indicating a depressive-like phenotype. Treatment with C. sativa oil significantly reduced immobility time, suggesting an antidepressant effect similar to that of Escitalopram. The absence of differences in locomotor activity suggests that the depressive-like behavior identified in the forced swim test was not influenced by locomotor impairments. These findings highlight the therapeutic potential of C. sativa oil in managing MDD and reinforce the need for further studies to elucidate its mechanisms of action.
Keywords: Major depressive disorder; Maternal deprivation; Cannabis sativa
References
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. American Psychiatric Association; 2013.; doi: 10.1176/appi.books.9780890425596.
2. Evans-Lacko S, Aguilar-Gaxiola S, Al-Hamzawi A, et al. Socio-economic variations in the mental health treatment gap for people with anxiety, mood, and substance use disorders: results from the WHO World Mental Health (WMH) surveys. Psychol Med 2018;48(9):1560–1571; doi: 10.1017/S0033291717003336.
3. Franklin TB, Russig H, Weiss IC, et al. Epigenetic Transmission of the Impact of Early Stress Across Generations. Biol Psychiatry 2010;68(5):408–415; doi: 10.1016/j.biopsych.2010.05.036.
4. Nemeroff CB, Owens MJ. Treatment of mood disorders. Nat Neurosci 2002;5(S11):1068–1070; doi: 10.1038/nn943.
5. Frodl T, Reinhold E, Koutsouleris N, et al. Childhood Stress, Serotonin Transporter Gene and Brain Structures in Major Depression. Neuropsychopharmacology 2010;35(6):1383–1390; doi: 10.1038/npp.2010.8.
6. Maes M, Rachayon M, Jirakran K, et al. Role of T and B Lymphocyte Cannabinoid Type 1 and 2 Receptors in Major Depression and Suicidal Behaviors: Effects of in Vitro Cannabidiol Administration. 2023; doi: 10.1101/2023.04.19.23288847.
7. Morcuende A, García-Gutiérrez MS, Tambaro S, et al. Immunomodulatory Role of CB2 Receptors in Emotional and Cognitive Disorders. Front Psychiatry 2022;13:866052; doi: 10.3389/fpsyt.2022.866052.
8. Kupfer DJ, Frank E, Phillips ML. Major depressive disorder: new clinical, neurobiological, and treatment perspectives. The Lancet 2012;379(9820):1045–1055; doi: 10.1016/S0140-6736(11)60602-8.
9. Cunha MDF, Gandini RDC. Adesão e não-adesão ao tratamento farmacológico para depressão. Psicol Teor E Pesqui 2009;25(3):409–418; doi: 10.1590/S0102-37722009000300015.
10. Poleszak E, Wośko S, Sławińska K, et al. Cannabinoids in depressive disorders. Life Sci 2018;213:18–24; doi: 10.1016/j.lfs.2018.09.058.
11. Ferber SG, Namdar D, Hen-Shoval D, et al. The “Entourage Effect”: Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders. Curr Neuropharmacol 2020;18(2):87–96; doi: 10.2174/1570159X17666190903103923.
12. Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects. Br J Pharmacol 2011;163(7):1344–1364; doi: 10.1111/j.1476-5381.2011.01238.x.
13. Carvalho PM de M, Moreira MM, de Oliveira MNA, et al. The psychiatric impact of the novel coronavirus outbreak. Psychiatry Res 2020;286:112902; doi: 10.1016/j.psychres.2020.112902.
14. Ferrarini EG, Paes RS, Baldasso GM, et al. Broad-spectrum cannabis oil ameliorates reserpine-induced fibromyalgia model in mice. Biomed Pharmacother 2022;154:113552; doi: 10.1016/j.biopha.2022.113552.
15. Montgomery SA, Loft H, Sánchez C, et al. Escitalopram (S-Enantiomer of Citalopram): Clinical Efficacy and Onset of Action Predicted from a Rat Model: ESCITALOPRAM: CLINICAL EFFICACY AND ONSET OF ACTION. Pharmacol Toxicol 2008;88(5):282–286; doi: 10.1111/j.1600-0773.2001.880511.x.
16. Bertollo AG, Mingoti MED, Medeiros J, et al. Hydroalcoholic Extract of Centella Asiatica and Madecassic Acid Reverse Depressive-like Behaviors, Inflammation and Oxidative Stress in Adult Rats Submitted to Stress in Early Life. 2024; doi: 10.21203/rs.3.rs-3800401/v1.
17. Djordjevic J, Djordjevic A, Adzic M, et al. Chronic Social Isolation Compromises the Activity of Both Glutathione Peroxidase and Catalase in Hippocampus of Male Wistar Rats. Cell Mol Neurobiol 2010;30(5):693–700; doi: 10.1007/s10571-009-9493-0.
18. Vuralli D, Wattiez A-S, Russo AF, et al. Behavioral and cognitive animal models in headache research. J Headache Pain 2019;20(1):11; doi: 10.1186/s10194-019-0963-6.
19. Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977;229(2):327–336.
20. Anacker C, O’Donnell KJ, Meaney MJ. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function. Dialogues Clin Neurosci 2014;16(3):321–333; doi: 10.31887/DCNS.2014.16.3/canacker.
21. Ignácio ZM, Réus GZ, Abelaira HM, et al. Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation. Behav Brain Res 2017;320:225–232; doi: 10.1016/j.bbr.2016.11.044.
22. Marais L, van Rensburg SJ, van Zyl JM, et al. Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus. Neurosci Res 2008;61(1):106–112; doi: 10.1016/j.neures.2008.01.011.
23. Lukkes JL, Mokin MV, Scholl JL, et al. Adult rats exposed to early-life social isolation exhibit increased anxiety and conditioned fear behavior, and altered hormonal stress responses. Horm Behav 2009;55(1):248–256; doi: 10.1016/j.yhbeh.2008.10.014.
24. Bogdanova OV, Kanekar S, D’Anci KE, et al. Factors influencing behavior in the forced swim test. Physiol Behav 2013;118:227–239; doi: 10.1016/j.physbeh.2013.05.012.
25. Hoffman KL. What Can Animal Models Tell Us about Depressive Disorders? In: Modeling Neuropsychiatric Disorders in Laboratory Animals Elsevier; 2016; pp. 35–86; doi: 10.1016/B978-0-08-100099-1.00002-9.
26. Dionisie V, Ciobanu AM, Toma VA, et al. Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress. Int J Mol Sci 2021;22(14):7483; doi: 10.3390/ijms22147483.
27. Seo MK, Lee JG, Park SW. Effects of escitalopram and ibuprofen on a depression-like phenotype induced by chronic stress in rats. Neurosci Lett 2019;696:168–173; doi: 10.1016/j.neulet.2018.12.033.
28. Réus GZ, Stringari RB, Ribeiro KF, et al. Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala. Acta Neuropsychiatr 2011;23(5):241–248; doi: 10.1111/j.1601-5215.2011.00579.x.
29. Bhunia S, Kolishetti N, Arias AY, et al. Cannabidiol for neurodegenerative disorders: A comprehensive review. Front Pharmacol 2022;13:989717; doi: 10.3389/fphar.2022.989717.
30. Detke MJ, Johnson J, Lucki I. Acute and chronic antidepressant drug treatment in the rat forced swimming test model of depression. Exp Clin Psychopharmacol 1997;5(2):107–112; doi: 10.1037/1064-1297.5.2.107.
31. Page ME, Detke MJ, Dalvi A, et al. Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology (Berl) 1999;147(2):162–167; doi: 10.1007/s002130051156.
32. Abdul Aziz NU, Chiroma SM, Mohd Moklas MA, et al. Antidepressant-Like Properties of Fish Oil on Postpartum Depression-Like Rats Model: Involvement of Serotonergic System. Brain Sci 2020;10(10):733; doi: 10.3390/brainsci10100733.
33. Krügel U, Fischer J, Radicke S, et al. Antidepressant effects of TNF-α blockade in an animal model of depression. J Psychiatr Res 2013;47(5):611–616; doi: 10.1016/j.jpsychires.2013.01.007.
34. Khanzode SD, Dakhale GN, Khanzode SS, et al. Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep 2003;8(6):365–370; doi: 10.1179/135100003225003393.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Revista Brasileira de Cannabis
This work is licensed under a Creative Commons Attribution 4.0 International License.
