Pollyana Mendonça de Assis
1 
, Eduarda Gomes Ferrarini
2,3, Gabriela Mantovani Baldasso
2, Rodrigo Sebben Paes
2, Murilo Chaves Gouvêa
4, Carlos Espínola Neto Segundo
4, Francesca Borrelli
5, Marcos Antônio Fernandes Brandão
1, Raffaelle Capasso
6,7, Rafael Cypriano Dutra
2,3* , Nádia Rezende Barbosa Raposo
1* 1 Center of Research and Innovation in Health Sciences (NUPICS), School of Pharmacy, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-330, Brazil.
2 Laboratory of Autoimmunity and Immunopharmacology (LAIF), Department of Health Sciences, Campus Araranguá, Universidade Federal de Santa Catarina, Araranguá 88906-072, Brazil.
3 Post-Graduate Program of Neuroscience, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, Brazil.
4 Associação Brasileira de Apoio Cannabis e Esperança – ABRACE, Parque Sólon de Lucena, 697, João Pessoa 58028-470, Brazil.
5 Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.
6 Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy.
7 Endocannabinoid Research Group, Naples, Italy.
Abstract
Background: Posttraumatic stress disorder (PTSD) is a psychiatric condition that manifests through a broad range of symptoms and shares several phenotypes with anxiety and depression. Refractory PTSD affects 10–30% of the patients and highlights the need for alternative pharmacotherapy. The suggested involvement of the endocannabinoid system (ECS) with the emotional processes has enlightened the use of Cannabis sp. Then, this study aimed to evaluate the therapeutic effects of a broad-spectrum Cannabis oil on anxiety- and depressive-like behaviors triggered by stressors from combined nature. In addition, this study investigated the effect of the oil on central cannabinoid receptor 1 and serum levels of cytokines, chemokines, and growth factors.
Methods: Mice were randomized into five groups (vehicle; Cannabis oil; fluoxetine; single oral dose) and submitted to acute restraint and chronic unpredictable stress. Then, they were behaviorally assessed in the elevated plus-maze test (EPMT), forced swimming test (FST), splash test (ST), and open field test (OFT). The tetrad cannabinoid assay evaluated the central effect of the oil. Serum biomarkers levels were measured by a multiplex bead-based assay.
Results: Cannabis oil (0.1 mg/kg, p.o.) significantly reduced the anxiety-like behavior in EPMT in the acute restraint stress model (p < 0.05) as compared to vehicle. Moreover, compared to the vehicle, Cannabis oil significantly reverted the despair and anhedonic-like behaviors in FST (p < 0.05) and ST (p < 0.05), respectively, in chronically stressed mice. Yet, compared to vehicle, therapy with Cannabis oil did not induce cannabinoid-tetrad (p < 0.0001); downregulated granulocyte-macrophage colony-stimulating factor (GM-CSF; p < 0.01) and advanced glycation end-products (RAGE; p < 0.0001); and upregulated vascular endothelial growth factor (VEGF; p < 0.01) serum levels.
Conclusion: Altogether, our data suggest the potential of the broad-spectrum Cannabis oil to improve symptoms related to anxiety and depression caused by traumatic events.