Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway

Renard, Justine; Loureiro, Michaël; Rosen, Laura G.; Zunder, Jordan; Oliveira, Cleusa De; Schmid, Susanne; Rushlow, Walter; Laviolette, Steven R.

doi:10.1523/jneurosci.3387-15.2016

Cited by 112 publications

(115 citation statements)

References 62 publications

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“…42 Seus sintomas incluem delírios, alucinações e distúrbios cognitivos, 39 com manifestações tipicamente no início da idade adulta ou no final da adolescência. 56 Desde a introdução clínica da última geração de antipsicóticos atípicos na década de 1990, poucas opções clinicamente significativas de tratamento novo para a esquizofrenia emergiram, a despeito de ser uma doença incapacitante, multidimensional e, portanto, de necessidade premente por novos fármacos seguros e eficazes.…”

Section: Esquizofreniaunclassified

“…42 Os fármacos atualmente disponíveis, atuam primariamente no bloqueio dos receptores dopaminérgicos do subtipo D2 mesolímbico e mesocortical, um mecanismo que não é entendido para tratar a causa subjacente ou distúrbio neuroquímico. 28,39 Os fármacos antipsicóticos típicos, a exemplo do haloperidol (18), exibem elevada afinidade nos receptores D2, induzindo a efeitos motores secundários (e.g. tremor), enquanto que os antipsicóticos atípicos, representados pela clozapina (19,Figura 11), são terapeuticamente eficazes não exibindo nenhum efeito secundário.…”

Section: Esquizofreniaunclassified

“…36 O efeito do CBD (2) é comparável ao haloperidol em termos de redução do tônus induzido pela apomorfina, porém sem os efeitos colaterais extrapiramidais, mesmo em altas doses. 11,39 Dada à necessidade de reduzir os efeitos colaterais dos antipsicóticos comerciais e contornar sua baixa eficácia em alguns sintomas esquizofrênicos, os canabinoides, especialmente o THC e o CBD têm sido sugeridos como candidatos promissores ao tratamento alternativo da esquizofrenia. 39 12 Neste sentido, já há dados que mostram que a concentração de receptores CB1 nas áreas associadas à fisiopatologia da doença é aumentada em indivíduos esquizofrênicos.…”

Section: Esquizofreniaunclassified

“…11,39 Dada à necessidade de reduzir os efeitos colaterais dos antipsicóticos comerciais e contornar sua baixa eficácia em alguns sintomas esquizofrênicos, os canabinoides, especialmente o THC e o CBD têm sido sugeridos como candidatos promissores ao tratamento alternativo da esquizofrenia. 39 12 Neste sentido, já há dados que mostram que a concentração de receptores CB1 nas áreas associadas à fisiopatologia da doença é aumentada em indivíduos esquizofrênicos. 56 De um modo geral, o foco atual dos estudos da ação do CBD (2) tem sido direcionado, principalmente, nos combate aos sintomas positivos e negativos da esquizofrenia, em detrimento dos sintomas cognitivos, contra os quais os antipsicóticos atuais não tem grande eficácia.…”

Section: Esquizofreniaunclassified

“…41 Outros estudos comportamentais e neuroquímicos sugerem que CBD (2) tem um perfil farmacológico semelhante ao dos antipsicóticos atípicos. 36,39,42 Neste contexto, os resultados já disponíveis fortalecem a necessidade de avanços e investimentos em pesquisa nesta área, buscando um melhor entendimento do sistema canabinoide, de sua farmacologia e na busca por novos canabinoides naturais e sintéticos, visando sua aplicação clínica e ampliação do arsenal terapêutico disponível em doenças psíquicas e neurodegenerativas.…”

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The Contribution of Studies with Canabidiol and Synthetic Analogues in the Design of New Drug Candidates for Neuropsychiatric Disorders and Neurodegenerative Diseases

Viegas¹,

Franco²

2017

Rev. Virtual Quim.

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Abstract:The first documented use of Cannabis for therapeutic purposes is dated from 2300 BC, with indications for the treatment of constipation, gout, beriberi, malaria, rheumatism and menstrual impairment. The search for therapeutic effects of Cannabis has already been pursued by scientists for over 50 years, and in the last 10 years, a new phase studies has started about marijuana constituents, such as Δ 9 -tetrahydrocannabinol (THC, 1) and cannabidiol (CBD, 2) for medicinal application. CBD is present in about 40% in the crude extract of Cannabis sativa, besides other 60 types of cannabinoids and a number of noncannabinoid constituents, accounting for approximately three hundred secondary metabolites. In spite of CBD being a constituent of Cannabis, it is deprived of the typical effects of the plant, differently from THC that induces anxiety and psychotic effects, being its main psychoactive component. Recent studies suggest that CBD could acts as a THC modulator in the brain, exhibiting anxiolytic and/or antipsychotic effects, antagonizing some undesirable effects of THC, as well as contributing with analgesic, antiemetic and antineoplastic, also affecting synapsis plasticity and facilitating neurogenesis. In this context, the scientific literature reinforces the need of advances and more investments in this research field, aiming a better knowledge about endocannabinoid system and the search for new natural and synthetic cannabinoids, supporting their use in the clinics and improving the available therapeutic arsenal for psychiatric and neurodegenerative diseases. Current data from studies dedicated to an improved understanding of its pharmacology and potential therapeutic applications, suggest that CBD and its analogues could play a singular role in the modulation of molecular targets related to central nervous system disorders, making possible the development of innovative, safer and efficient drugs for the treatment of non-responsive patients to the conventional clinics, with significant improvement in life quality and, perhaps, their cure.Keywords: Cannabidiol; cannabinoids; neuropsychiatric disorders; neurodegenerative diseases. ResumoO primeiro uso documentado da Cannabis para fins terapêuticos é datado de aproximadamente 2300 a.C., para o tratamento de constipação, gota, beribéri, malária, reumatismo e problemas menstruais. A busca por efeitos terapêuticos da Cannabis já recebe atenção de cientistas há mais de 50 anos, sendo que nos últimos 10 anos, tem-se observado uma nova fase de estudos acerca dos o po e tes da a o ha, a e e plo do Δ 9 -tetraidrocanabinol (THC, 1) e do canabidiol (CBD, 2) para uso medicinal. O CBD ocorre em cerca de 40% no extrato bruto de Cannabis sativa, além de outros 60 tipos de canabinoides e inúmeros constituintes não-canabinoides, totalizando cerca de 300 metabólitos secundários. O CBD, apesar de ser um constituinte da Cannabis, é desprovido dos efeitos típicos da planta, diferentemente do THC que induz a ansiedade e efeitos psicóticos, sendo o principal ingrediente psico...

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Section: Esquizofreniaunclassified

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The Contribution of Studies with Canabidiol and Synthetic Analogues in the Design of New Drug Candidates for Neuropsychiatric Disorders and Neurodegenerative Diseases

Viegas¹,

Franco²

2017

Rev. Virtual Quim.

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Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine

Spelta,

Real,

Bruno

et al. 2024

J of Neuroscience Research

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Despite evidence of the beneficial effects of cannabidiol (CBD) in animal models of cocaine use disorder (CUD), CBD neuronal mechanisms remain poorly understood. This study investigated the effects of CBD treatment on brain glucose metabolism, in a CUD animal model, using [18F]FDG positron emission tomography (PET). Male C57Bl/6 mice were injected with cocaine (20 mg/kg, i.p.) every other day for 9 days, followed by 8 days of CBD administration (30 mg/kg, i.p.). After 48 h, animals were challenged with cocaine. Control animals received saline/vehicle. [18F]FDG PET was performed at four time points: baseline, last day of sensitization, last day of withdrawal/CBD treatment, and challenge. Subsequently, the animals were euthanized and immunohistochemistry was performed on the hippocampus and amygdala to assess the CB1 receptors, neuronal nuclear protein, microglia (Iba1), and astrocytes (GFAP). Results showed that cocaine administration increased [18F]FDG uptake following sensitization. CBD treatment also increased [18F]FDG uptake in both saline and cocaine groups. However, animals that were sensitized and challenged with cocaine, and those receiving only an acute cocaine injection during the challenge phase, did not exhibit increased [18F]FDG uptake when treated with CBD. Furthermore, CBD induced modifications in the integrated density of NeuN, Iba, GFAP, and CB1R in the hippocampus and amygdala. This is the first study addressing the impact of CBD on brain glucose metabolism in a preclinical model of CUD using PET. Our findings suggest that CBD disrupts cocaine‐induced changes in brain energy consumption and activity, which might be correlated with alterations in neuronal and glial function.

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Proteomics and Lipidomics in the Elucidation of Endocannabinoid Signaling in Healthy and Schizophrenia Brains

et al. 2018

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Interest in the modulation of endocannabinoid signaling has increased since the discovery of receptors for compounds of Cannabis sativa. Endocannabinoids are crucial neuromodulators of many brain functions and changes in the ligands and their receptors have been associated with psychiatric disorders, such as schizophrenia. Genetic, neuroimaging, and behavioral studies have reinforced the role of endocannabinoids in the pathobiology of schizophrenia. However, molecular pathways and biological processes involved in cannabinoid effects are not totally understood. Additionally, the endocannabinoid signaling network with other non-cannabinoid targets, and the effects of phytocannabinoids increase the complexity to understand their role in schizophrenia and homeostasis conditions. Thus, proteomic studies can provide evidence about the involvement of cannabinoid receptors, as well as the metabolic and synthetic enzymes of the endocannabinoids in these disorders. Additionally, quantification of endocannabinoids in the blood serum or cerebrospinal fluid can be a useful approach to identify new biomarkers in schizophrenia, and lipidomic techniques can be used to quantify these compounds. Herein, the authors review proteomic and lipidomic studies that have been used for analysis of the endocannabinoid system in healthy and schizophrenia function. The findings may contribute to understand the involvement of endocannabinoids in the brain and in the neurobiological basis of schizophrenia.

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Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway

Cited by 112 publications

References 62 publications

The Contribution of Studies with Canabidiol and Synthetic Analogues in the Design of New Drug Candidates for Neuropsychiatric Disorders and Neurodegenerative Diseases

The Contribution of Studies with Canabidiol and Synthetic Analogues in the Design of New Drug Candidates for Neuropsychiatric Disorders and Neurodegenerative Diseases

Impact of cannabidiol on brain glucose metabolism of C57Bl/6 male mice previously exposed to cocaine

Proteomics and Lipidomics in the Elucidation of Endocannabinoid Signaling in Healthy and Schizophrenia Brains

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