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1.
Support Care Cancer ; 29(1): 49-66, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32734392

RESUMEN

PURPOSE: Taste and smell disturbances in patients affected by cancer are very common, but often under-recognized symptoms. If not addressed properly, they may impact nutritional status, food enjoyment, and quality of life. Treatment tools available for clinicians to manage chemosensory alterations are limited and are often based on personal clinical experiences. The aim of this study was to assess current oncological and palliative care literature through a scoping review, in order to identify available treatments for taste and smell alterations in cancer patients. METHODS: Medline, Embase, CINAHL, ProQuest Dissertations and Theses, and Google Scholar were searched from inception until January 2020, with subject headings relevant to the domains of chemosensory alterations, palliative, and cancer care. A total of 10,718 English and French language publications were reviewed, yielding 43 articles on the researched topic. RESULTS: The heterogeneity of selected articles led to difficulties in interpretation and analysis of the available evidence. Included publications differed in study design, population sample, anticancer treatments, and measures of assessment for taste and smell disturbances. A broad variety of treatment options were described including zinc and polaprezinc, radio-protectors, vitamins and supplements, anti-xerostomia agents, active swallowing exercises, nutritional interventions, delta-9-tetrahydrocannabinol, and photobiomodulation. CONCLUSION: This scoping review identifies the current state of knowledge regarding chemosensory alterations within supportive cancer care. Despite not reaching firm conclusions, this article offers therapeutic venues to further explore in larger and more methodologically sound studies.


Asunto(s)
Trastornos del Olfato/tratamiento farmacológico , Olfato/fisiología , Trastornos del Gusto/tratamiento farmacológico , Gusto/fisiología , Adulto , Amifostina/uso terapéutico , Carnosina/análogos & derivados , Carnosina/uso terapéutico , Dronabinol/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Estado Nutricional/fisiología , Trastornos del Olfato/patología , Compuestos Organometálicos/uso terapéutico , Cuidados Paliativos/métodos , Calidad de Vida/psicología , Selenio/uso terapéutico , Trastornos del Gusto/patología , Compuestos de Zinc/uso terapéutico
2.
Brasília; CONITEC; nov. 2020.
No convencional en Portugués | BRISA/RedTESA | ID: biblio-1145537

RESUMEN

INTRODUÇÃO: Esclerose múltipla (EM) é uma doença neurológica crônica, inflamatória, que ocorre em pessoas geneticamente suscetíveis. A doença é caracterizada por infiltração de células imunes, perda de mielina e axônios e formação de placas multifocais no cérebro e medula espinhal. A prevalência média global da EM é de 33 por 100.000 pessoas, com variação entre os diferentes países. As taxas de prevalência no Brasil variaram de 1,36/100.000 a 27,2/100.000 habitantes dependendo da região. A espasticidade, percebida pelos pacientes como rigidez e espasmos musculares, é um sintoma comum na EM e está associado ao comprometimento funcional que pode exacerbar outros sintomas e reduzir a qualidade de vida. A espasticidade ocorre entre 60 a 84% dos pacientes, sendo os sintomas mais comuns associados: rigidez, espasmos e restrições de mobilidade, que ocorrem em cerca de três quartos dos pacientes, avaliados pelos médicos. Outros sintomas comuns incluem fadiga, dor e disfunção da bexiga. O tratamento não farmacológico geralmente inclui evitar fatores desencadeantes e fisioterapia regular. No Sistema Único de Saúde (SUS) está disponível para tratamento da espasticidade, de acordo com o Protocolo Clínico e Diretrizes Terapêuticas de Espasticidade, duas apresentações de toxina botulínica tipo A. A literatura descreve outros tratamentos como baclofeno, tizanidina e gabapentina. PERGUNTA: Tetraidrocanabinol + canabidiol (Mevatyl®) é eficaz e seguro para o tratamento da espasticidade moderada à grave associada à EM em pacientes adultos? EVIDÊNCIAS CLÍNICAS: Após a análise das evidências apresentadas pelo demandante foram incluídos sete ensaios clínicos, uma análise derivada de ensaio clínico e uma revisão sistemática. O demandante apresentou uma meta-análise, no entanto, como alguns estudos permitiram doses superiores a 12 sprays/dia, mesmo que a dose média dos estudos tenha sido menor que a estabelecida em bula, a Secretaria Executiva da Conitec optou por refazer as análises separando estes estudos. Em todas as avaliações, o THC:CBD foi associado a uma melhora média maior da espasticidade quando avaliada pela escala de Ashworth em comparação com o placebo, mão não foi estatisticamente significativo. Quando avaliada pela escala subjetiva foi associado a uma melhora significativa. Adicionalmente, o THC:CBD proporcionou uma redução significativa de ≥ 30% no escore de espasticidade avaliada pela escala NRS, considerada uma diferença clinicamente importante. A evidência foi considerada de baixa qualidade. AVALIAÇÃO ECONÔMICA: Com o preço proposto para incorporação de R$ 1.445,24, o custo mensal de THC:CBD como adjuvante a terapia padrão seria de R$ 1.597,36. Foi estimado um ganho de 0,55 anos de vida ajustados pela qualidade a mais com o tratamento com THC:CBD comparado ao tratamento padrão isolado, e 1,98 meses de controle da doença a mais que a terapia padrão. O custo incremental do tratamento com THC:CBD ao longo de 30 anos foi estimado em R$ 11.724,82 a mais que o custo do tratamento padrão, resultando em uma RCEI de R$21.271,79/QALY. O custo incremental por mês de controle da doença foi de R$ 5.438,76, resultando em uma RCEI de R$2.743,29/mês de espasticidade controlada. Há incertezas no desfecho por QALY pois a na estimativa da utilidade não incluiu população brasileira. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: O demandante estimou que entre 823 a 859 pacientes seriam elegíveis e teriam acesso ao medicamento em cinco anos, com impacto orçamentário ao SUS estimado entre R$ 1,3 milhões, chegando a R$ 9,1 milhões no último ano dependendo da difusão de mercado adotada (Caso-base: 10% ao ano e Caso-alternativo: primeiro ano de 25%, com crescimento de 10% ao ano até 65% em 5 anos). Entretanto, foram identificadas algumas discrepâncias na população do modelo apresentado pelo demandante, com a população passando para 918 no primeiro ano a 958 no quinto ano. O impacto orçamentário utilizando a distribuição de mercado do caso-base, no primeiro ano seria de R$ 1,49 milhão, chegando a R$ 7,8 milhões em cinco anos. Já para o cenário do caso alternativo, no primeiro ano o impacto seria de 3,7 milhões e no quinto ano, com 65% dos pacientes recebendo o tratamento, 10,14 milhões. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Para a elaboração desta seção, realizaram-se buscas estruturadas nos campos de pesquisa das bases de dados ClinicalTrials.gov e Cortellis™, a fim de localizar medicamentos potenciais para tratamento sintomático da espasticidade moderada a grave relacionada à esclerose múltipla. Dessa forma, foram detectados dois medicamentos potenciais para a indicação terapêutica em questão, o arbaclofeno e o dronabinol. CONSIDERAÇÕES FINAIS: O THC:CBD proporciona uma diminuição da espasticidade subjetiva quando comparados com placebo, mas não apresentou nenhuma alteração na espasticidade medida objetivamente (escalas de Ashworth e Ashworth modificada). Embora o número total de eventos adversos seja maior que o placebo, o medicamento foi seguro no tratamento da espasticidade em pacientes com EM. As evidências foram consideradas de baixa qualidade. Não há evidências de estudos que avaliem a eficácia de canabinoides em comparação com outros tratamentos ativos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: No dia 06 de agosto de 2020, em sua 89ª reunião de plenário, os membros da Conitec recomendaram preliminarmente a não incorporação da associação tetraidrocanabinol + canabidiol como tratamento adjuvante para melhoria dos sintomas de pacientes adultos com espasticidade moderada a grave devido à esclerose múltipla que não responderam adequadamente a outra terapia. O plenário considerou que o medicamento só apresentou benefício quando avaliado por escala subjetiva e a ausência de eficácia do fitofármaco na redução da espasticidade por escala objetiva comparado ao placebo, além disso os estudos apresentaram médio a alto risco de viés, o que tornou a evidência de baixa qualidade. A matéria foi disponibilizada em consulta pública. CONSULTA PÚBLICA: o Relatório de Recomendação da Conitec foi disponibilizado por meio da Consulta Pública nº 04/2020 entre os dias 15/09/2020 e 05/10/2020. Foram recebidas 306 contribuições, sendo 4 técnico-científicas e 302 contribuições de experiência ou opinião. Os principais temas presentes nas contribuições de experiência e opinião foram referentes a: eficácia; qualidade de vida; melhora da dor e segurança do tratamento. Foram recebidas referências estudos científicos, no entanto não foram consideradas no presente documento por não se enquadrarem na pergunta PICO. A Beaufour Ipsen Ltda - empresa fabricante da tecnologia avaliada reforçou os dados de eficácia do THC:CBD na redução da gravidade da espasticidade relacionada à EM e sintomas associados, como espasmos ou distúrbios do sono. Também abordaram a validade da escala NRS, por se tratar de muitas vezes ser desfecho primário dos estudos clínicos, incluindo ensaios controlados e de vida real e se tratar de um desfecho centrado no paciente com relevância clínica. Com relação a parte econômica, o demandante retrata que realizou vários cenários na avaliação de custo-efetividade: 1) inclusão de probabilidade e de custos relacionados a eventos adversos; 2) utilização do desfecho clínico NRS ≥ 30% (diferença clinicamente importante); 3) sub análise considerando o fornecimento gratuito de Mevatyl® no primeiro mês de tratamento; 5) comparador baclofeno, tizanidina e diazepam. No entanto, de modo geral, os resultados sofreram poucas alterações em relação àquelas apresentadas no documento de submissão. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da Conitec presentes na 92ª reunião ordinária, no dia 03 de novembro de 2020, deliberaram por unanimidade recomendar a não incorporação tetraidrocanabinol (THC) 27 mg/ml + canabidiol (CBD) 25 mg/ml como tratamento adjuvante para melhoria dos sintomas de pacientes adultos com espasticidade moderada a grave devido à esclerose múltipla que não responderam adequadamente a outra terapia. Os membros presentes na reunião consideraram que não houve evidências adicionais para mudar a recomendação preliminar e que ainda há incertezas sobre a eficácia do fitofármaco. Também foi pontuado que existem outros tratamentos para espasticidade, assim há uma necessidade de avaliação ampla dessas tecnologias. Foi assinado o Registro de Deliberação nº 572/2020. DECISÃO: Não incorporar o tetraidrocanabinol 27mg/ml + canabidiol 25mg/ml para o tratamento sintomático da espasticidade moderada a grave relacionada à esclerose múltipla, no âmbito do Sistema Único de Saúde - SUS, conforme Portaria nº 59, publicada no Diário Oficial da União nº 228, seção 1, página 717, em 1º de dezembro de 2020.


Asunto(s)
Humanos , Dronabinol/uso terapéutico , Cannabidiol/uso terapéutico , Esclerosis Múltiple/etiología , Espasticidad Muscular/tratamiento farmacológico , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía
3.
Int J Mol Sci ; 21(17)2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32872332

RESUMEN

Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.


Asunto(s)
Apoptosis/efectos de los fármacos , Betacoronavirus/fisiología , Agonistas de Receptores de Cannabinoides/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Citocinas/inmunología , Dronabinol/uso terapéutico , Neumonía Viral/tratamiento farmacológico , /tratamiento farmacológico , Anciano , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Enterotoxinas/efectos adversos , Femenino , Humanos , Pulmón/inmunología , Pulmón/virología , Masculino , Ratones , Ratones Endogámicos C3H , MicroARNs/genética , Persona de Mediana Edad , Pandemias , Neumonía/tratamiento farmacológico , Neumonía/virología , Neumonía Viral/mortalidad , Neumonía Viral/virología , /virología , Transducción de Señal/efectos de los fármacos
4.
J Pharmacol Exp Ther ; 374(3): 462-468, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32561684

RESUMEN

Attenuating emesis elicited by both disease and medical treatments of disease remains a critical public health challenge. Although cannabinergic medications have been used in certain treatment-resistant populations, Food and Drug Administration-approved cannabinoid antiemetics are associated with undesirable side effects, including cognitive disruption, that limit their prescription. Previous studies have shown that a metabolically stable analog of the endocannabinoid anandamide, methanandamide (mAEA), may produce lesser cognitive disruption than that associated with the primary psychoactive constituent in cannabis, Δ9-tetrahydrocannabinol (Δ9-THC), raising the possibility that endocannabinoids may offer a therapeutic advantage over currently used medications. The present studies were conducted to evaluate this possibility by comparing the antiemetic effects of Δ9-THC (0.032-0.1 mg/kg) and mAEA (3.2-10.0 mg/kg) against nicotine- and lithium chloride (LiCl)-induced emesis and prodromal hypersalivation in squirrel monkeys. Pretreatment with 0.1 mg/kg Δ9-THC blocked nicotine-induced emesis and reduced hypersalivation in all subjects and blocked LiCl-induced emesis and reduced hypersalivation in three of four subjects. Pretreatment with 10 mg/kg mAEA blocked nicotine-induced emesis in three of four subjects and LiCl-induced emesis in one of four subjects and reduced both nicotine- and LiCl-induced hypersalivation. Antiemetic effects of Δ9-THC and mAEA were reversed by rimonabant pretreatment, providing verification of cannabinoid receptor type 1 mediation. These studies systematically demonstrate for the first time the antiemetic effects of cannabinoid agonists in nonhuman primates. Importantly, although Δ9-THC produced superior antiemetic effects, the milder cognitive effects of mAEA demonstrated in previous studies suggest that it may provide a favorable treatment option under clinical circumstances in which antiemetic efficacy must be balanced against side effect liability. SIGNIFICANCE STATEMENT: Emesis has significant evolutionary value as a defense mechanism against ingested toxins; however, it is also one of the most common adverse symptoms associated with both disease and medical treatments of disease. The development of improved antiemetic pharmacotherapies has been impeded by a paucity of animal models. The present studies systematically demonstrate for the first time the antiemetic effects of the phytocannabinoid Δ9-tetrahydrocannabinol and endocannabinoid analog methanandamide in nonhuman primates.


Asunto(s)
Antieméticos/farmacología , Agonistas de Receptores de Cannabinoides/farmacología , Animales , Antieméticos/uso terapéutico , Ácidos Araquidónicos/farmacología , Ácidos Araquidónicos/uso terapéutico , Agonistas de Receptores de Cannabinoides/uso terapéutico , Dronabinol/farmacología , Dronabinol/uso terapéutico , Interacciones Farmacológicas , Masculino , Receptor Cannabinoide CB1/agonistas , Saimiri , Salivación/efectos de los fármacos , Vómitos/tratamiento farmacológico
5.
Orv Hetil ; 161(25): 1035-1041, 2020 06.
Artículo en Húngaro | MEDLINE | ID: mdl-32516121

RESUMEN

Cannabis belongs to the highly prominent soft drugs; after coffee, tobacco and alcohol, it is considered to be the fourth most consumed psychoactive substance. The two most common cannabinoids are the strictly regulated psychotropic delta-9-tetrahydrocannabinol and the dietary supplement cannabidiol, which is non-psychoactive, only subject to reporting obligation and accessible in Hungary since 2004. In relation to the application of medical cannabis, especially in oncological indications, many misconceptions have arisen. In our review, we summarize the history of cannabis, the mechanism of action, the current evidences for application in oncological indications, the legal regulations, and highlight the potential concerns regarding cannabis administration. Orv Hetil. 2020; 161(25): 1035-1041.


Asunto(s)
Cannabinoides , Cannabis , Dronabinol/uso terapéutico , Marihuana Medicinal , Neoplasias/terapia , Humanos , Hungría , Oncología Médica
6.
Obstet Gynecol ; 135(6): 1289-1295, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32459420

RESUMEN

OBJECTIVE: To evaluate whether prophylactic dronabinol, a synthetic tetrahydrocannabinol, reduces pain during medical abortion. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of women undergoing medical abortion with mifepristone and misoprostol up through 70 days of gestation. All participants received 800 mg of ibuprofen and were randomized to either 5 mg of oral dronabinol or a placebo 30 minutes before misoprostol administration. Participants used a text messaging service to report pain on a numeric rating scale from 0 to 10 (0=no pain, 10=worst pain). The primary outcome was maximum pain experienced during the 24 hours after misoprostol administration. Secondary outcomes were pain scores at 0, 6, and 24 hours after misoprostol administration; maximum anxiety and nausea scores; use of additional pain medication; reported side effects; and satisfaction (yes or no). We needed 68 participants (34 per group) to have 80% power to detect a 2-point difference in maximum pain on a numeric rating scale. RESULTS: From November 2018 to May 2019, we randomized 70 women (dronabinol=35, placebo=35). Participants in the study arms had comparable baseline characteristics. We found no difference between groups in the median maximum pain score reported (dronabinol 7 [interquartile range 6-8], placebo 7 [interquartile range 5-8], P=.82) or median pain scores at any timepoint. Groups were also no different in mean maximum anxiety (dronabinol 3.33 [SD 3.06], placebo 3.23 [SD 2.53], P=.88) or nausea scores (dronabinol 2.21 [SD 2.32], placebo 2.72 [SD 2.64], P=.41). Most women were satisfied with their pain management (76% dronabinol, 82% placebo, P=.51). CONCLUSION: Dronabinol does not reduce the maximum level of pain experienced by women undergoing medical abortion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03604341.


Asunto(s)
Aborto Inducido/efectos adversos , Analgésicos no Narcóticos/uso terapéutico , Dronabinol/uso terapéutico , Ibuprofeno/uso terapéutico , Dolor/prevención & control , Adulto , Analgésicos no Narcóticos/administración & dosificación , Método Doble Ciego , Dronabinol/administración & dosificación , Femenino , Humanos , Ibuprofeno/administración & dosificación , Dolor/etiología , Manejo del Dolor , Embarazo , Adulto Joven
9.
Psychopharmacology (Berl) ; 237(6): 1813-1826, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32162103

RESUMEN

RATIONALE: Excessive fear and anxiety, coupled with corticolimbic dysfunction, are core features of stress- and trauma-related psychopathology, such as posttraumatic stress disorder (PTSD). Interestingly, low doses of ∆9-tetrahydrocannabinol (THC) can produce anxiolytic effects, reduce threat-related amygdala activation, and enhance functional coupling between the amygdala and medial prefrontal cortex and adjacent rostral cingulate cortex (mPFC/rACC) during threat processing in healthy adults. Together, these findings suggest the cannabinoid system as a potential pharmacological target in the treatment of excess fear and anxiety. However, the effects of THC on corticolimbic functioning in response to threat have not be investigated in adults with trauma-related psychopathology. OBJECTIVE: To address this gap, the present study tests the effects of an acute low dose of THC on corticolimbic responses to threat in three groups of adults: (1) non-trauma-exposed healthy controls (HC; n = 25), (2) trauma-exposed adults without PTSD (TEC; n = 27), and (3) trauma-exposed adults with PTSD (n = 19). METHODS: Using a randomized, double-blind, placebo-controlled, between-subjects design, 71 participants were randomly assigned to receive either THC or placebo (PBO) and subsequently completed a well-established threat processing paradigm during functional magnetic resonance imaging. RESULTS: In adults with PTSD, THC lowered threat-related amygdala reactivity, increased mPFC activation during threat, and increased mPFC-amygdala functional coupling. CONCLUSIONS: These preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.


Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Dronabinol/farmacología , Miedo/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Trastornos por Estrés Postraumático/tratamiento farmacológico , Adulto , Amígdala del Cerebelo/diagnóstico por imagen , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Método Doble Ciego , Dronabinol/uso terapéutico , Miedo/psicología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Corteza Prefrontal/diagnóstico por imagen , Trastornos por Estrés Postraumático/diagnóstico por imagen , Trastornos por Estrés Postraumático/psicología
10.
Arch. argent. pediatr ; 118(1): 64-67, 2020-02-00.
Artículo en Inglés, Español | LILACS, BINACIS | ID: biblio-1095682

RESUMEN

En los últimos años, se ha observado un incremento significativo en el interés por la prescripción del cannabis medicinal. En el siguiente artículo, se informa acerca de la escasa base científica que avala la prescripción de estos compuestos en un listado amplio y diverso de patologías médicas. Se considera fundamental que cualquier sustancia que vaya a ser utilizada en humanos siga un protocolo de aprobación estricto y científico, que pueda desligarse de modas o de resultados individuales. Es necesario que, antes de la prescripción de una droga en personas, deba tenerse un panorama claro de cuáles son los usos del compuesto en cuestión, pero, sobre todo, de su seguridad, que es prácticamente desconocida en el cannabis medicinal.


In recent years, the interest in medical cannabis prescription has increased significantly. This article provides information about the little scientific basis supporting the prescription of these products for a wide and diverse range of medical conditions. It is critical for any substance to be used in human beings to follow a strict scientific approval protocol, detached from any trend or individual outcome. Before prescribing any drug to human beings, it is necessary to have a clear picture of its uses, especially its safety, which is practically unknown in the case of medical cannabis.


Asunto(s)
Humanos , Cannabidiol/efectos adversos , Cannabidiol/uso terapéutico , Marihuana Medicinal/efectos adversos , Marihuana Medicinal/uso terapéutico , Seguridad , Dronabinol/uso terapéutico , Cannabidiol/farmacología , Ensayos de Uso Compasivo , Legislación de Medicamentos
11.
Support Care Cancer ; 28(5): 2095-2103, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31916006

RESUMEN

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a burdensome adverse event frequently associated with chemotherapy treatment of cancer. Evidence suggests that cannabinoid CB2 receptors are present in brainstem neurons, and thus, there may exist a role for cannabinoids to counter CINV. The aim of this paper is to conduct a systematic review and meta-analysis of the efficacy and safety of oral cannabinoids compared with other treatments as documented in randomized controlled trials (RCTs). METHODS: A literature search was conducted using Ovid MEDLINE up until December 31, 2018; Embase Classic and Embase up until 2018 week 53; and Cochrane Central Register of Controlled Trials up until November 2018. Study data were extracted and included in this meta-analysis if they reported on at least one of the following efficacy endpoints: no nausea and no vomiting, no nausea, and no vomiting. The Mantel-Haenszel method and random effects analysis model were used, to generate odds ratio (OR) and accompanying 95% confidence intervals (CI). RESULTS: In the setting of prophylactic treatment against both nausea and vomiting, oral cannabinoid was more efficacious than placebo or other studied antiemetic treatments. When controlling for vomiting, oral cannabinoid was equally as efficacious as others. Against nausea, oral cannabinoid was equally as effective as other treatments. A greater percentage of patients administered oral cannabinoid for CINV experienced dysphoria, euphoria, and sedation. CONCLUSION: Although there exists some evidence suggesting that oral cannabinoids may have a role in controlling for emesis from a neurophysiological perspective, these conclusions are currently not mirrored in the published RCTs to date. However, there exists only a limited number of RCTs, comparisons with older treatment regimens and a lack of standard reporting practice across published literature. Further RCTs should investigate the efficacy and safety of oral cannabinoids, to secure a better picture of the efficacy of oral cannabinoids against CINV.


Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Cannabinoides/uso terapéutico , Náusea/tratamiento farmacológico , Vómitos/tratamiento farmacológico , Adulto , Dronabinol/análogos & derivados , Dronabinol/uso terapéutico , Humanos , Quimioterapia de Inducción/efectos adversos , Náusea/inducido químicamente , Neoplasias/tratamiento farmacológico , Receptor Cannabinoide CB2/efectos de los fármacos , Vómitos/inducido químicamente
12.
Clin Toxicol (Phila) ; 58(2): 124-128, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31111749

RESUMEN

Introduction: Although over half of US states have legalized marijuana for medical indications, there is limited research in use in the pediatric population. The objective was to evaluate the disposition of oral tetrahydrocannabinol (THC) in children receiving cannabis extracts for pediatric epilepsy.Methods: Prospective, observational study, evaluating the disposition of oral THC in children receiving cannabis extracts. Subjects were less than 18 years of age, receiving oral cannabis for pediatric epilepsy. Subjects included in the study had at least 2 detectable THC and related metabolite plasma concentrations during serial blood draw over a 10-12 h study period.Results: Nine subjects with a median age of 11 years (IQR 4.75) were included in the study, with oral doses ranging from 0.02 mg/kg to 1.59 mg/kg. Peak plasma concentrations (0.8 to 3.6 ng/ml) in most patients were achieved within 2 hours, while acute phase elimination half-life ranged from 1 to 5 hours. THC-COOH and glucuronide remained elevated through the study period. There was significant variation between the dose ingested and peak concentrations (R2 = 0.05).Conclusion: In pediatric patients receiving oral THC cannabis extracts, mean time to peak plasma concentrations was 2-7 hours, while mean acute phase elimination half-life was 4.0 hours. THC-COOH and THC-COOH glucuronide metabolites persisted throughout the 10-12 hour study period. Large variation and no correlation was noted between dose of THC by weight and peak concentrations, suggesting variation of bioavailability amongst pediatric population or inaccurate reporting of THC contents.


Asunto(s)
Dronabinol/sangre , Epilepsia/tratamiento farmacológico , Marihuana Medicinal/sangre , Administración Oral , Disponibilidad Biológica , Niño , Dronabinol/uso terapéutico , Epilepsia/sangre , Semivida , Humanos , Marihuana Medicinal/uso terapéutico , Tasa de Depuración Metabólica , Estudios Prospectivos , Distribución Tisular
13.
J Geriatr Psychiatry Neurol ; 33(4): 175-184, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31547752

RESUMEN

The endocannabinoid system has been a target of interest for agitation in Alzheimer disease (AD) because of potential behavioral effects and its potential impact on mechanisms implicated in AD such as oxidative stress (OS) and neuroinflammation. We explored whether serum markers of OS and neuroinflammation were associated with response to the cannabinoid nabilone in agitated patients with AD (N = 38). All participants were enrolled in a 14-week, double-blind, cross-over trial comparing nabilone to placebo (6 weeks each) with a 1-week washout between phases. Samples were collected at the start and end of each phase. The cross-sectional relationship agitation (Cohen Mansfield Agitation Inventory) and OS and inflammatory markers were investigated to select markers of interest. Significant markers were then explored for their relationship with response. The OS marker, 4-hydroxynonenal (4-HNE; F1, 35 = 6.41, P = .016), and the proinflammatory cytokine, tumor necrosis factor-α (TNF-α; F1, 29 = 3.97, P = .06), were associated with agitation severity, and TNF-α remained significantly associated (F2, 25 = 3.69, P = .04) after adjustment for cognition. In the placebo phase, lower baseline 4-HNE was associated with decreases in agitation severity only (b = 0.01, P = .01), while lower baseline TNF-α was associated with decreases in agitation severity in the nabilone phase only (b = 1.14, P = .045). Changes in 4-HNE were not associated with changes in agitation severity in either phase. In the nabilone phase, lower baseline TNF-α was associated with decreases in agitation severity (b = 1.14, P = .045), and decreases in TNF-α were associated with decreases in agitation severity (b = 1.12, P = .006). These findings suggest that OS and neuroinflammation may be associated with agitation severity, while nabilone may have anti-inflammatory effects.


Asunto(s)
Enfermedad de Alzheimer/complicaciones , Cognición/efectos de los fármacos , Citocinas/uso terapéutico , Dronabinol/análogos & derivados , Estrés Oxidativo/fisiología , Agitación Psicomotora/tratamiento farmacológico , Anciano , Biomarcadores/sangre , Dronabinol/uso terapéutico , Femenino , Humanos , Masculino , Agitación Psicomotora/complicaciones
14.
Nat Rev Neurol ; 16(1): 9-29, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31831863

RESUMEN

Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the endocannabinoidome - that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma.


Asunto(s)
Cannabinoides/metabolismo , Endocannabinoides/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/metabolismo , Analgésicos/metabolismo , Analgésicos/uso terapéutico , Animales , Cannabidiol/metabolismo , Cannabidiol/uso terapéutico , Cannabinoides/uso terapéutico , Dronabinol/metabolismo , Dronabinol/uso terapéutico , Combinación de Medicamentos , Endocannabinoides/uso terapéutico , Humanos , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB2/metabolismo
15.
Psychopharmacology (Berl) ; 237(2): 479-490, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31712969

RESUMEN

RATIONALE: Depression is common among individuals with cannabis use disorder (CUD), particularly individuals who present to CUD treatment. Treatments that consider this comorbidity are essential. OBJECTIVES: The goal of this secondary analysis was to examine whether N-acetylcysteine (NAC) reduced depressive symptoms among adults (age 18-50) with CUD (N = 302) and whether the effect of NAC on cannabis cessation varied as a result of baseline levels of depression. Bidirectional associations between cannabis use amount and depression were also examined. METHODS: Data for this secondary analysis were from a National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) multi-site clinical trial for CUD. Adults with CUD (N = 302) were randomized to receive 2400 mg of NAC daily or matched placebo for 12 weeks. All participants received abstinence-based contingency management. Cannabis quantity was measured by self-report, and weekly urinary cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) confirmed abstinence. Depressive symptoms were measured by the Hospital Anxiety and Depression Scale. RESULTS: Depressive symptoms did not differ between the NAC and placebo groups during treatment. There was no significant interaction between treatment and baseline depression predicting cannabis abstinence during treatment. Higher baseline depression was associated with decreased abstinence throughout treatment and a significant gender interaction suggested that this may be particularly true for females. Cross-lagged panel models suggested that depressive symptoms preceded increased cannabis use amounts (in grams) during the subsequent month. The reverse pathway was not significant (i.e., greater cannabis use preceding depressive symptoms). CONCLUSIONS: Results from this study suggest that depression may be a risk factor for poor CUD treatment outcome and therefore should be addressed in the context of treatment. However, results do not support the use of NAC to concurrently treat co-occurring depressive symptoms and CUD in adults. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01675661.


Asunto(s)
Acetilcisteína/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/psicología , Abuso de Marihuana/tratamiento farmacológico , Abuso de Marihuana/psicología , Acetilcisteína/farmacología , Adulto , Cannabis , Comorbilidad , Depresión/epidemiología , Método Doble Ciego , Dronabinol/uso terapéutico , Femenino , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/uso terapéutico , Humanos , Masculino , Abuso de Marihuana/epidemiología , Motivación/efectos de los fármacos , Motivación/fisiología , Resultado del Tratamiento , Adulto Joven
16.
Clin Toxicol (Phila) ; 58(2): 75-81, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31062643

RESUMEN

Background: Tetrahydrocannabinol (THC) is a psychoactive cannabinoid that has been used to treat various conditions. However, due to various adverse effects, its widespread promotion and use has been controversial. It is this aspect (encouraged by various state legislatures) that forms the basis for an edited debate between an Integrative Family Medicine physician and a Medical Toxicologist.Methods: Pro/Con debate with literature review and commentary.Discussion: Medical THC is beneficial for various conditions (especially pain relief). However the dosing, titration and delivery system has of yet to be precisely defined. There is a paucity of studies focusing on cannabidiol (CBD) efficacy without THC, which further complicates medical cannabis clinical studies. Cannabis toxicity tends to be cumulative, which makes it more difficult to identify at the bedside.Conclusion: There is conflicting data regarding the efficacy and toxicity of medical use of THC.


Asunto(s)
Dronabinol , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Marihuana Medicinal , Dronabinol/uso terapéutico , Dronabinol/toxicidad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Humanos , Marihuana Medicinal/uso terapéutico , Marihuana Medicinal/toxicidad
17.
Am J Drug Alcohol Abuse ; 45(6): 580-595, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31687845

RESUMEN

Background: Pain is the most frequent indication for which medical cannabis treatment is sought.Objectives: The clinical potential of cannabis and cannabis-derived products (CDPs) relies on their efficacy to treat an indication and potential adverse effects that impact outcomes, including abuse liability and neurocognitive effects. To ascertain the extent to which these effects impact therapeutic utility, studies investigating cannabis and CDPs for pain were reviewed for analgesic efficacy and assessments of abuse liability and neurocognitive effects.Methods: A comprehensive review of placebo-controlled studies investigating cannabis and CDP analgesia was performed. Methods and findings related to adverse effects, abuse liability, and neurocognitive effects were extracted.Results: Thirty-eight studies were reviewed; 29 assessed cannabis and CDPs for chronic pain, 1 for acute pain, and 8 used experimental pain tests. Most studies ascertained adverse effects through self-report (N = 27). Fewer studies specifically probed abuse liability (N = 7) and cognitive and psychomotor effects (N = 12). Many studies related to chronic and experimental pain (N = 18 and N = 5, respectively) found cannabis and CDPs to reduce pain. Overall, adverse effects were mild to moderate, and dose-related. Studies investigating the impact of cannabis and CDPs on abuse liability and neurocognitive endpoints were mostly limited to inhaled administration and confirmed dose-related effects.Conclusion: Few studies investigating cannabis and CDP analgesia assess abuse liability and cognitive endpoints, adverse effects that impact the long-term clinical utility of these drugs. Future studies should include these measures to optimize research and clinical care related to cannabis-based therapeutics.


Asunto(s)
Analgésicos no Narcóticos/uso terapéutico , Cannabinoides/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Marihuana Medicinal/uso terapéutico , Dolor Agudo/tratamiento farmacológico , Cannabidiol/uso terapéutico , Dronabinol/uso terapéutico , Humanos , Abuso de Marihuana/etiología , Pruebas de Estado Mental y Demencia , Desempeño Psicomotor , Ensayos Clínicos Controlados Aleatorios como Asunto
18.
Eur J Pharmacol ; 865: 172806, 2019 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-31738934

RESUMEN

Δ9-THC suppresses cisplatin-induced vomiting through activation of cannabinoid CB1 receptors. Cisplatin-evoked emesis is predominantly due to release of serotonin and substance P (SP) in the gut and the brainstem which subsequently stimulate their corresponding 5-HT3-and neurokinin NK1-receptors to induce vomiting. Δ9-THC can inhibit vomiting caused either by the serotonin precursor 5-HTP, or the 5-HT3 receptor selective agonist, 2-methyserotonin. In the current study, we explored whether Δ9-THC and related CB1/CB2 receptor agonists (WIN55,212-2 and CP55,940) inhibit vomiting evoked by SP (50 mg/kg, i.p.) or the NK1 receptor selective agonist GR73632 (5 mg/kg, i.p.). Behavioral methods were employed to determine the antiemetic efficacy of cannabinoids in least shrews. Our results showed that administration of varying doses of Δ9-THC (i.p. or s.c.), WIN55,212-2 (i.p.), or CP55,940 (i.p.) caused significant suppression of SP-evoked vomiting in a dose-dependent manner. When tested against GR73632, Δ9-THC also dose-dependently reduced the evoked emesis. The antiemetic effect of Δ9-THC against SP-induced vomiting was prevented by low non-emetic doses of the CB1 receptor inverse-agonist/antagonist SR141716A (<10 mg/kg). We also found that the NK1 receptor antagonist netupitant can significantly suppress vomiting caused by a large emetic dose of SR141716A (20 mg/kg). In sum, Δ9-THC and related cannabinoids suppress vomiting evoked by the nonselective (SP) and selective (GR73632) neurokinin NK1 receptor agonists via stimulation of cannabinoid CB1 receptors.


Asunto(s)
Benzoxazinas/uso terapéutico , Agonistas de Receptores de Cannabinoides/uso terapéutico , Cannabinoides/uso terapéutico , Ciclohexanoles/uso terapéutico , Dronabinol/uso terapéutico , Morfolinas/uso terapéutico , Naftalenos/uso terapéutico , Receptores de Neuroquinina-1/fisiología , Vómitos/tratamiento farmacológico , Animales , Femenino , Masculino , Fragmentos de Péptidos/farmacología , Musarañas , Sustancia P/análogos & derivados , Sustancia P/farmacología , Vómitos/inducido químicamente
19.
Int J Mol Sci ; 20(21)2019 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-31661848

RESUMEN

A history of allergies doubles the risk of vulvodynia-a chronic pain condition of unknown etiology often accompanied by increases in numbers of vulvar mast cells. We previously established the biological plausibility of this relationship in mouse models where repeated exposures to the allergens oxazolone or dinitrofluorobenzene on the labiar skin or inside the vaginal canal of ND4 Swiss Webster outbred mice led to persistent tactile sensitivity and local increases in mast cells. In these models, depletion of mast cells alleviated pain. While exposure to cleaning chemicals has been connected to elevated vulvodynia risk, no single agent has been linked to adverse outcomes. We sensitized female mice to methylisothiazolinone (MI)-a biocide preservative ubiquitous in cosmetics and cleaners-dissolved in saline on their flanks, and subsequently challenged them with MI or saline for ten consecutive days in the vaginal canal. MI-challenged mice developed persistent tactile sensitivity, increased vaginal mast cells and eosinophils, and had higher serum Immunoglobulin E. Therapeutic and preventive intra-vaginal administration of Δ9-tetrahydrocannabinol reduced mast cell accumulation and tactile sensitivity. MI is known to cause skin and airway irritation in humans, and here we provide the first pre-clinical evidence that repeated MI exposures can also provoke allergy-driven genital pain.


Asunto(s)
Cosméticos/toxicidad , Dermatitis Alérgica por Contacto/etiología , Mastocitos/efectos de los fármacos , Conservadores Farmacéuticos/toxicidad , Tiazoles/toxicidad , Vagina/efectos de los fármacos , Alérgenos , Animales , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Dermatitis Alérgica por Contacto/epidemiología , Dronabinol/uso terapéutico , Femenino , Humanos , Inmunoglobulina E/sangre , Mastocitos/metabolismo , Ratones , Membrana Mucosa , Dolor/inducido químicamente , Piel , Vagina/inmunología
20.
Integr Cancer Ther ; 18: 1534735419881498, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31595793

RESUMEN

Background: Cancer-related cachexia and anorexia syndrome (CACS) is a common phenomenon in cancer patients. Cannabis has been suggested to stimulate appetite but research on this issue has yielded mixed results. The current study aimed to evaluate the effect of dosage-controlled cannabis capsules on CACS in advanced cancer patients. Methods: The cannabis capsules used in this study contained two fractions of oil-based compounds. The planned treatment was 2 × 10 mg per 24 hours for six months of tetrahydrocannabinol (THC) 9.5 mg and cannabidiol (CBD) 0.5 mg. If patients suffered from side effects, dosage was reduced to 5 mg × 2 per day (THC 4.75 mg, CBD 0.25 mg). Participants were weighed on every physician visit. The primary objective of the study was a weight gain of ≥10% from baseline. Results: Of 24 patients who signed the consent form, 17 started the cannabis capsules treatment, but only 11 received the capsules for more than two weeks. Three of six patients who completed the study period met the primary end-point. The remaining three patients had stable weights. In quality of life quaternaries, patients reported less appetite loss after the cannabis treatment (p=0.05). Tumor necrosis factor-α (TNF-α) levels decreased after the cannabis treatment but without statistical significance. According to patients' self-reports, improvement in appetite and mood as well as a reduction in pain and fatigue was demonstrated. Conclusions: Despite various limitations, this preliminary study demonstrated a weight increase of ≥10% in 3/17 (17.6%) patients with doses of 5mgx1 or 5mgx2 capsules daily, without significant side effects. The results justify a larger study with dosage-controlled cannabis capsules in CACS.


Asunto(s)
Anorexia/tratamiento farmacológico , Caquexia/tratamiento farmacológico , Cannabidiol/uso terapéutico , Cannabis/química , Cápsulas/uso terapéutico , Dronabinol/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Analgésicos/uso terapéutico , Anorexia/etiología , Caquexia/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Proyectos Piloto , Calidad de Vida , Autoinforme
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