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1.
Arch Toxicol ; 98(6): 1877-1890, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38494580

RESUMO

Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship.


Assuntos
Canabidiol , Cannabis , Relação Dose-Resposta a Droga , Emulsões , Fígado , Ratos Wistar , Animais , Masculino , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Canabidiol/toxicidade , Canabidiol/administração & dosagem , Cannabis/química , Dronabinol/toxicidade , Dronabinol/administração & dosagem , Ratos , Nanopartículas/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia
2.
Biochem Pharmacol ; 157: 294-303, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30077641

RESUMO

The increased use of cannabis as a therapeutic drug in recent years has raised some concerns due to its potential effects on reproductive health. With regards to the male, the endocannabinoid system is involved in the spermatogenesis and in the sperm function. The chronic use of tetrahidrocannabinol (THC) has been associated with sperm anomalies, decreased sperm motility and structural changes in the testis. However, whether THC affects sperms ability to fertilize and to generate embryos remains unclear. The aim of this study was to evaluate this effect using a mice model of THC chronic treatment. For this purpose, a chronic treatment with THC was carried out. Mice were randomly allocated into two groups: an experimental group treated with a daily dose of 10 mg/kg-body weight THC for a period of 30 days and a control group treated with a vehicle. The THC-mice cortex showed a significant decrease of mRNA of Cnr1 compared to control-mice while, in the testis, the expression of Cnr1 was not affected. The weight of testis and epididymis and the histological analysis did not show any change between groups. On the other hand, no changes were observed in the sperm motility or the sperm concentration. The chronic use of THC did not generate any methylation change in the three CpG regions of Cnn1 analysed, neither in the brain nor in the embryos generated by in vitro fertilization (IVF). Finally, the embryo production by IVF was no different using spermatozoa from both THC and control mice. This work contradicts the belief that THC consumption has a negative effect on male reproductive processes.


Assuntos
Dronabinol/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Apoptose , Peso Corporal/efeitos dos fármacos , Encéfalo/metabolismo , Dronabinol/farmacocinética , Embrião de Mamíferos/metabolismo , Epididimo/anatomia & histologia , Epigênese Genética , Fertilização in vitro/efeitos dos fármacos , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Regiões Promotoras Genéticas , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Testículo/anatomia & histologia , Testículo/metabolismo
3.
Braz J Psychiatry ; 30(1): 69-76, 2008 Mar.
Artigo em Português | MEDLINE | ID: mdl-18373021

RESUMO

OBJECTIVE: Cannabis is the most used illicit drug worldwide, however only a few studies have examined cognitive deficits related to its use. Clinical manifestations associated with those deficits include a motivational syndrome, impairment in cognitive flexibility, inattention, deficits in abstract reasoning and concept formation, aspects intimately related to the executive functions, which potentially exert a central role in substance dependence. The objective was to make a review about consequences of cannabis use in executive functioning. METHOD: This review was carried out on reports drawn from MedLine, SciELO, and Lilacs. DISCUSSION: In studies investigating acute use effects, higher doses of tetrahydrocannabinol are associated to impairments in performance of nonsevere users in planning and control impulse tasks. However, chronic cannabis users do not show those impairments. Although demonstration of residual effects of cannabis in the executive functioning is controversial, persistent deficits seem to be present at least in a subgroup of chronic users after 28 days of abstinence. CONCLUSIONS: The neuropsychological studies found did not have as a main aim the evaluation of executive functioning. A criterial selection of standardized neuropsychological tests, more appropriate study designs as well as concomitant investigations with structural and functional neuroimaging techniques may improve the understanding of eventual neurotoxicity associated with cannabis use.


Assuntos
Canabinoides/farmacologia , Transtornos Cognitivos/induzido quimicamente , Cognição/efeitos dos fármacos , Abuso de Maconha/psicologia , Fumar Maconha/efeitos adversos , Atenção/efeitos dos fármacos , Transtornos Cognitivos/fisiopatologia , Formação de Conceito/efeitos dos fármacos , Tomada de Decisões , Dronabinol/toxicidade , Lobo Frontal/efeitos dos fármacos , Humanos , Comportamento Impulsivo/induzido quimicamente , Comportamento Impulsivo/fisiopatologia , Comportamento Impulsivo/psicologia , Fumar Maconha/fisiopatologia , Fumar Maconha/psicologia , Testes Neuropsicológicos
4.
Artigo em Português | LILACS | ID: lil-482130

RESUMO

OBJETIVO: A maconha é a droga ilícita mais consumida no mundo, porém ainda existem poucos estudos examinando eventuais prejuízos cognitivos relacionados ao seu uso. As manifestações clínicas associadas a esses déficits incluem síndrome amotivacional, prejuízo na flexibilidade cognitiva, desatenção, dificuldade de raciocínio abstrato e formação de conceitos, aspectos intimamente ligados às funções executivas, as quais potencialmente exercem um papel central na dependência de substâncias. O objetivo do estudo foi fazer uma revisão a respeito das implicações do uso da maconha no funcionamento executivo. MÉTODO: Esta revisão foi conduzida utilizando-se bases de dados eletrônicas (MedLine, Pubmed, SciELO and Lilacs). DISCUSSÃO: Em estudos de efeito agudo, doses maiores de tetrahidrocanabinol encontram-se associadas a maior prejuízo no desempenho de usuários leves em tarefas de controle inibitório e planejamento; porém, este efeito dose-resposta não ocorre em usuários crônicos. Embora haja controvérsias no que se refere a efeitos residuais da maconha, déficits persistentes parecem estar presentes após 28 dias de abstinência, ao menos em um subgrupo de usuários crônicos. CONCLUSÕES: Os estudos encontrados não tiveram como objetivo principal a avaliação das funções executivas. A seleção de testes padronizados, desenhos de estudos mais apropriados e o uso concomitante com técnicas de neuroimagem estrutural e funcional podem auxiliar na melhor compreensão das conseqüências deletérias do uso crônico da maconha no funcionamento executivo.


OBJECTIVE: Cannabis is the most used illicit drug worldwide, however only a few studies have examined cognitive deficits related to its use. Clinical manifestations associated with those deficits include amotivational syndrome, impairment in cognitive flexibility, inattention, deficits in abstract reasoning and concept formation, aspects intimately related to the executive functions, which potentially exert a central role in substance dependence. The objective was to make a review about consequences of cannabis use in executive functioning. METHOD: This review was carried out on reports drawn from MedLine, SciELO, and Lilacs. DISCUSSION: In studies investigating acute use effects, higher doses of tetrahydrocannabinol are associated to impairments in performance of nonsevere users in planning and control impulse tasks. However, chronic cannabis users do not show those impairments. Although demonstration of residual effects of cannabis in the executive functioning is controversial, persistent deficits seem to be present at least in a subgroup of chronic users after 28 days of abstinence. CONCLUSIONS: The neuropsychological studies found did not have as a main aim the evaluation of executive functioning. A criterial selection of standardized neuropsychological tests, more appropriate study designs as well as concomitant investigations with structural and functional neuroimaging techniques may improve the understanding of eventual neurotoxicity associated with cannabis use.


Assuntos
Humanos , Canabinoides/farmacologia , Transtornos Cognitivos/induzido quimicamente , Cognição/efeitos dos fármacos , Abuso de Maconha/psicologia , Fumar Maconha/efeitos adversos , Atenção/efeitos dos fármacos , Transtornos Cognitivos/fisiopatologia , Formação de Conceito/efeitos dos fármacos , Tomada de Decisões , Lobo Frontal/efeitos dos fármacos , Comportamento Impulsivo/induzido quimicamente , Comportamento Impulsivo/fisiopatologia , Comportamento Impulsivo/psicologia , Fumar Maconha/fisiopatologia , Fumar Maconha/psicologia , Testes Neuropsicológicos , Dronabinol/toxicidade
5.
Rev. farm. bioquim. Univ. Säo Paulo ; 29(2): 55-61, jul.-dez. 1993. ilus, tab
Artigo em Português | LILACS | ID: lil-135288

RESUMO

A Cannabis (maconha) tem sido utilizada como droga de abuso por varias decadas, ocupando o primeiro lugar entre as drogas ilicitas usadas atualmente em todo o mundo. Sendo seu uso proibido entre nos, e de importancia forense a identificacao do usuario atraves da analise toxicologica do componente principal responsavel pela psicoatividade da droga (THC) bem como de seu principal produto de biotransformacao (THC-COOH) em amostras biologicas. Com a finalidade de fornecer informacoes a respeito dos aspectos botanicos, quimicos, farmacologicos, toxicologicos bem como da legislacao vigente de aspecto legal preparou-se esta monografia


Assuntos
Humanos , Botânica , Cannabis , Química , Canabinoides/farmacologia , Dronabinol/toxicidade , Drogas Ilícitas
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