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1.
Viruses ; 13(7)2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206839

RESUMO

The persistence of human immunodeficiency virus-1 (HIV)-associated neurocognitive disorders (HAND) in the era of effective antiretroviral therapy suggests that modern HIV neuropathogenesis is driven, at least in part, by mechanisms distinct from the viral life cycle. Identifying more subtle mechanisms is complicated by frequent comorbidities in HIV+ populations. One of the common confounds is substance abuse, with cannabis being the most frequently used psychoactive substance among people living with HIV. The psychoactive effects of cannabis use can themselves mimic, and perhaps magnify, the cognitive deficits observed in HAND; however, the neuromodulatory and anti-inflammatory properties of cannabinoids may counter HIV-induced excitotoxicity and neuroinflammation. Here, we review our understanding of the cross talk between HIV and cannabinoids in the central nervous system by exploring both clinical observations and evidence from preclinical in vivo and in vitro models. Additionally, we comment on recent advances in human, multi-cell in vitro systems that allow for more translatable, mechanistic studies of the relationship between cannabinoid pharmacology and this uniquely human virus.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Canabinoides/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/terapia , HIV-1/efeitos dos fármacos , Doenças Neuroinflamatórias/terapia , Animais , Fármacos Anti-HIV/farmacologia , Canabinoides/farmacologia , Canabinoides/normas , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Técnicas In Vitro , Camundongos , Psicotrópicos/farmacologia , Psicotrópicos/normas , Psicotrópicos/uso terapêutico
2.
Clin Chem Lab Med ; 58(5): 673-681, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-31527291

RESUMO

Background The widespread availability of cannabis raises concerns regarding its effect on driving performance and operation of complex equipment. Currently, there are no established safe driving limits regarding ∆9-tetrahydrocannabinol (THC) concentrations in blood or breath. Daily cannabis users build up a large body burden of THC with residual excretion for days or weeks after the start of abstinence. Therefore, it is critical to have a sensitive and specific analytical assay that quantifies THC, the main psychoactive component of cannabis, and multiple metabolites to improve interpretation of cannabinoids in blood; some analytes may indicate recent use. Methods A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to quantify THC, cannabinol (CBN), cannabidiol (CBD), 11-hydroxy-THC (11-OH-THC), (±)-11-nor-9-carboxy-Δ9-THC (THCCOOH), (+)-11-nor-Δ9-THC-9-carboxylic acid glucuronide (THCCOOH-gluc), cannabigerol (CBG), and tetrahydrocannabivarin (THCV) in whole blood (WB). WB samples were prepared by solid-phase extraction (SPE) and quantified by LC-MS/MS. A rapid and simple method involving methanol elution of THC in breath collected in SensAbues® devices was optimized. Results Lower limits of quantification ranged from 0.5 to 2 µg/L in WB. An LLOQ of 80 pg/pad was achieved for THC concentrations in breath. Calibration curves were linear (R2>0.995) with calibrator concentrations within ±15% of their target and quality control (QC) bias and imprecision ≤15%. No major matrix effects or drug interferences were observed. Conclusions The methods were robust and adequately quantified cannabinoids in biological blood and breath samples. These methods will be used to identify cannabinoid concentrations in an upcoming study of the effects of cannabis on driving.


Assuntos
Canabinoides/análise , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Testes Respiratórios , Canabidiol/análise , Canabidiol/sangue , Canabidiol/isolamento & purificação , Canabidiol/normas , Canabinoides/sangue , Canabinoides/isolamento & purificação , Canabinoides/normas , Cromatografia Líquida de Alta Pressão/normas , Ácido Cítrico/química , Dronabinol/análise , Dronabinol/sangue , Dronabinol/isolamento & purificação , Dronabinol/normas , Glucose/análogos & derivados , Glucose/química , Humanos , Limite de Detecção , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Fumar , Extração em Fase Sólida , Espectrometria de Massas em Tandem/normas , Estudos de Validação como Assunto
3.
Medicina (Kaunas) ; 55(11)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752240

RESUMO

Background and Objectives: Neuroinflammation is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this study, we investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of two non-psychoactive phytocannabinoids, cannabigerol (CBG) and cannabidiol (CBD). Materials and Methods: The motoneuron-like cell line NSC-34 differentiated by serum deprivation and with the additional treatment of all-trans retinoic acid (RA) is a valid model to investigate molecular events linked to neurodegeneration in ALS. Results: Pre-treatment with CBG (at 2.5 and 5 µM doses) alone and in combination with CBD (at 2.5 and 5 µM doses) was able to reduce neuroinflammation induced by a culture medium of LPS-stimulated macrophages. In particular, the pre-treatment with CBD at a 5 µM dose decreased TNF-α levels and increased IL10 and IL-37 expression. CBG-CBD association at a 5 µM dose also reduced NF-kB nuclear factor activation with low degradation of the inhibitor of kappaB alpha (IkBα). CBG and CBD co-administered at a 5 µM dose decreased iNOS expression and increased Nrf2 levels. Furthermore, the pre-treatment with the association of two non-psychoactive cannabinoids downregulated Bax protein expression and upregulated Bcl-2 expression. Our data show the anti-inflammatory, anti-oxidant, and anti-apoptotic effects PPARγ-mediated. Conclusions: Our results provide preliminary support on the potential therapeutic application of a CBG-CBD combination for further preclinical studies.


Assuntos
Canabinoides/normas , Quimioterapia Combinada/normas , Inflamação/prevenção & controle , Neurônios/efeitos dos fármacos , Canabidiol/normas , Canabidiol/uso terapêutico , Canabinoides/uso terapêutico , Técnicas de Cultura de Células/métodos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Humanos , Fatores de Proteção
4.
Pain Manag Nurs ; 20(2): 107-112, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31036325

RESUMO

The current landscape contains conflicting reports regarding the use of medical marijuana, creating fields of misinformation and lack of understanding by health care providers about cannabinoids. In this article we provide a dispassionate look at medical marijuana, while providing a clinical overview focusing on pain management. We examine the mechanisms of the endocannabinoid system, along with the pharmacology of cannabinoids. Current research on the use of marijuana for the treatment of pain is reviewed. Finally, recommendations for pain management nurses on integrating research, clinical practice, and U.S. drug policy are made.


Assuntos
Canabinoides/normas , Manejo da Dor/tendências , Analgésicos/uso terapêutico , Canabinoides/uso terapêutico , Humanos , Manejo da Dor/métodos
5.
Pain Manag Nurs ; 20(3): 185-191, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30527857

RESUMO

OBJECTIVE: The objective of this paper is to review the available literature regarding the use of cannabis and cannabinoids in adult oncologic pain management. DESIGN AND DATA SOURCES: A integrative review was conducted on March 1, 2018 using PubMed, MEDLINE, CINAHL, Embase, and Scopus. A snowball method was used to extract studies included in systematic reviews that were not included in the primary literature search. REVIEW METHOD: Articles reviewed address the use of cannabinoids or cannabis for pain management in oncology patients, either as stand- alone or adjuvant therapy. RESULTS: The final number of articles included is nine articles. Of the nine studies reviewed, eight reviewed the effect of the cannabinoid THC on cancer pain, and one study reviewed the use of medicinally available whole plant cannabis. The following study types were included: multiple multi-center, randomized, placebo- controlled trials and two prospective observational survey studies. RESULTS AND CONCLUSIONS: Of the eight studies that reviewed the effect of the cannabinoid THC, five found THC to be more effective than placebo, one found THC to be more effective than placebo in American patients but ineffective in patients from other countries, and two found THC to be no more effective than placebo. The study that reviewed the effect of the whole plant cannabis found that there was a significant decrease in pain among those patients smoking cannabis. NURSING PRACTICE IMPLICATIONS: The lack of evidence in this field of research suggests a need to change policy surrounding cannabis research.


Assuntos
Dor do Câncer/tratamento farmacológico , Canabinoides/uso terapêutico , Cannabis/efeitos adversos , Adulto , Analgésicos/uso terapêutico , Dor do Câncer/fisiopatologia , Canabinoides/normas , Humanos , Manejo da Dor/efeitos adversos , Manejo da Dor/métodos , Manejo da Dor/normas
6.
Artigo em Inglês | MEDLINE | ID: mdl-29936369

RESUMO

In this study, we describe the development of a SFC-MS method for the quality control of cannabis plants that could be potentially adulterated with synthetic cannabinoids. Considering the high number of already available synthetic cannabinoids and the high rate of development of novel structures, we aimed to develop a generic method suitable for the analysis of a large panel of substances using seventeen synthetic cannabinoids from multiple classes as model compounds. Firstly, a suitable column was chosen after a screening phase. Secondly, optimal operating conditions were obtained following a robust optimization strategy based on a design of experiments and design space methodology (DoE-DS). Finally, the quantitative performances of the method were assessed with a validation according to the total error approach. The developed method has a run time of 9.4 min. It uses a simple modifier composition of methanol with 2% H2O and requires minimal sample preparation. It can chromatographically separate natural cannabinoids (except THC-A and CBD-A) from the synthetics assessed. Also, the use of mass spectrometry provides sensitivity and specificity. Moreover, this quality by design (QbD) approach permits the tuning of the method (within the DS) during routine analysis to achieve a desirable separation since the future compounds that should be analyzed could be unknown. The method was validated for the quantitation of a selected synthetic cannabinoid in fiber-type cannabis matrix over the range of 2.5% - 7.5% (w/w) with LOD value as low as 14.4 ng/mL. This generic method should be easy to implement in customs or QC laboratories in the context of counterfeit drugs tracking.


Assuntos
Canabinoides/análise , Cromatografia com Fluido Supercrítico/métodos , Espectrometria de Massas/métodos , Maconha Medicinal/análise , Maconha Medicinal/normas , Canabinoides/química , Canabinoides/normas , Contaminação de Medicamentos , Modelos Lineares , Reprodutibilidade dos Testes , Projetos de Pesquisa , Sensibilidade e Especificidade
8.
J Pharm Biomed Anal ; 150: 208-219, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29247961

RESUMO

There are at least 554 identified compounds in C. sativa L., among them 113 phytocannabinoids and 120 terpenes. Phytocomplex composition differences between the pharmaceutical properties of different medical cannabis chemotype have been attributed to strict interactions, defined as 'entourage effect', between cannabinoids and terpenes as a result of synergic action. The chemical complexity of its bioactive constituents highlight the need for standardised and well-defined analytical approaches able to characterise the plant chemotype, the herbal drug quality as well as to monitor the quality of pharmaceutical cannabis extracts and preparations. Hence, in the first part of this study an analytical procedures involving the combination of headspace-solid-phase microextraction (HS-SPME) coupled to GC-MS and High Resolution Mass-Spectrometry LC-HRMS (Orbitrap®) were set up, validated and applied for the in-depth profiling and fingerprinting of cannabinoids and terpenes in two authorised medical grade varieties of Cannabis sativa L. inflorescences (Bedrocan® and Bediol®) and in obtained macerated oils. To better understand the trend of all volatile compounds and cannabinoids during oil storage a new procedure for cannabis macerated oil preparation without any thermal step was tested and compared with the existing conventional methods to assess the potentially detrimental effect of heating on overall product quality.


Assuntos
Canabinoides/análise , Cannabis/química , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Inflorescência/química , Maconha Medicinal/análise , Extratos Vegetais/análise , Óleos de Plantas/análise , Microextração em Fase Sólida , Espectrometria de Massas por Ionização por Electrospray , Canabinoides/normas , Estabilidade de Medicamentos , Estudos de Viabilidade , Maconha Medicinal/normas , Extratos Vegetais/normas , Óleos de Plantas/normas , Controle de Qualidade , Reprodutibilidade dos Testes , Fatores de Tempo
10.
Clin Chem Lab Med ; 55(10): 1555-1563, 2017 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-28207408

RESUMO

BACKGROUND: Cannabis has been used since ancient times to relieve neuropathic pain, to lower intraocular pressure, to increase appetite and finally to decrease nausea and vomiting. The combination of the psychoactive cannabis alkaloid Δ9-tetrahydrocannabinol (THC) with the non-psychotropic alkaloids cannabidiol (CBD) and cannabinol (CBN) demonstrated a higher activity than THC alone. The Italian National Institute of Health sought to establish conditions and indications on how to correctly use nationally produced cannabis to guarantee therapeutic continuity in individuals treated with medical cannabis. METHODS: The evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil was conducted using an easy and fast ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. RESULTS: Extraction efficiency of oil was significantly higher than that of water with respect to the different cannabinoids. This was especially observed in the case of the pharmacologically active THC, CBD and their acidic precursors. Fifteen minutes boiling was sufficient to achieve the highest concentrations of cannabinoids in the cannabis tea solutions. At ambient temperature, a significant THC and CBD decrease to 50% or less of the initial concentration was observed over 3 and 7 days, respectively. When refrigerated at 4 °C, similar decreasing profiles were observed for the two compounds. The cannabinoids profile in cannabis oil obtained after pre-heating the flowering tops at 145 °C for 30 min in a static oven resulted in a complete decarboxylation of cannabinoid acids CBDA and THCA-A. Nevertheless, it was apparent that heat not only decarboxylated acidic compounds, but also significantly increased the final concentrations of cannabinoids in oil. The stability of cannabinoids in oil samples was higher than that in tea samples since the maximum decrease (72% of initial concentration) was observed in THC coming from unheated flowering tops at ambient temperature. In the case of the other cannabinoids, at ambient and refrigerated temperatures, 80%-85% of the initial concentrations were measured up to 14 days after oil preparation. CONCLUSIONS: As the first and most important aim of the different cannabis preparations is to guarantee therapeutic continuity in treated individuals, a strictly standardized preparation protocol is necessary to assure the availability of a homogeneous product of defined stability.


Assuntos
Canabinoides/análise , Cromatografia Líquida de Alta Pressão , Óleos de Plantas/química , Espectrometria de Massas em Tandem , Chá/química , Canabinoides/isolamento & purificação , Canabinoides/normas , Cannabis/química , Cannabis/metabolismo , Cromatografia Líquida de Alta Pressão/normas , Padrões de Referência , Espectrometria de Massas em Tandem/normas , Temperatura
11.
Ann Med ; 48(3): 128-41, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26912385

RESUMO

Herbal cannabis has been used for thousands of years for medical purposes. With elucidation of the chemical structures of tetrahydrocannabinol (THC) and cannabidiol (CBD) and with discovery of the human endocannabinoid system, the medical usefulness of cannabinoids has been more intensively explored. While more randomized clinical trials are needed for some medical conditions, other medical disorders, like chronic cancer and neuropathic pain and certain symptoms of multiple sclerosis, have substantial evidence supporting cannabinoid efficacy. While herbal cannabis has not met rigorous FDA standards for medical approval, specific well-characterized cannabinoids have met those standards. Where medical cannabis is legal, patients typically see a physician who "certifies" that a benefit may result. Physicians must consider important patient selection criteria such as failure of standard medical treatment for a debilitating medical disorder. Medical cannabis patients must be informed about potential adverse effects, such as acute impairment of memory, coordination and judgment, and possible chronic effects, such as cannabis use disorder, cognitive impairment, and chronic bronchitis. In addition, social dysfunction may result at work/school, and there is increased possibility of motor vehicle accidents. Novel ways to manipulate the endocannbinoid system are being explored to maximize benefits of cannabinoid therapy and lessen possible harmful effects.


Assuntos
Canabinoides/uso terapêutico , Cannabis/química , Endocanabinoides/metabolismo , Maconha Medicinal/uso terapêutico , Dor/tratamento farmacológico , Receptores de Canabinoides/metabolismo , Analgésicos não Narcóticos/uso terapêutico , Canabinoides/efeitos adversos , Canabinoides/normas , Controle de Medicamentos e Entorpecentes , Humanos , Abuso de Maconha/prevenção & controle , Maconha Medicinal/efeitos adversos , Maconha Medicinal/normas , Metanálise como Assunto , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos
13.
Bioanalysis ; 6(21): 2919-30, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25486237

RESUMO

BACKGROUND: Synthetic cannabinoids (SC) are widely-abused cannabimimetic drugs that do not screen positive in traditional cannabinoids immunoassays, making detection difficult. METHODS AND RESULTS: The first commercially-available immunoassay for urinary SC was validated. Limits of detection (5-20 µg/L), imprecision (<13.1% intra-, <37.7% inter-assay), and cross-reactivity profiles of 22 SC and 37 metabolites were obtained. A large negative bias (-80.8 to -28.0%) was observed. Sensitivity (98.3%), specificity (48.1%) and efficiency (53.9%) were determined from screening 20,017 urine specimens and confirming 1432 presumptive positive and 1069 selected negative specimens by LC-MS/MS. Cutoff optimization improved performance to 87.6% sensitivity, 85.2% specificity, and 85.4% efficiency. CONCLUSION: This high-throughput urine SC assay has good sensitivity and improved specificity and efficiency at modified cutoff concentrations.


Assuntos
Canabinoides/urina , Imunoensaio/métodos , Análise em Microsséries/métodos , Calibragem , Canabinoides/metabolismo , Canabinoides/normas , Reações Cruzadas , Humanos , Concentração de Íons de Hidrogênio , Imunoensaio/normas , Limite de Detecção , Análise em Microsséries/normas , Detecção do Abuso de Substâncias
14.
J Anal Toxicol ; 38(8): 563-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25217547

RESUMO

The case reports for 18 driving cases positive for the synthetic cannabinoid substances XLR-11 and/or UR-144 are discussed. Eleven of these cases had drug recognition expert evaluations performed. Slurred speech, lack of convergence and body and eyelid tremors were the most consistently noted interview characteristic. Pulse and blood pressure of the subjects were within the expected range. Most of the drivers contacted demonstrated poor driving; however, their performance on the standardized field sobriety tests yielded inconsistent diagnostic information. All cases were negative for other commonly detected drugs that affect the central nervous system, although one case was additionally positive for other synthetic cannabinoids. Of the studied cases, six were positive for only UR-144, whereas eight contained only XLR-11. Four cases were found to have both.


Assuntos
Condução de Veículo , Canabinoides/sangue , Indóis/sangue , Adolescente , Adulto , Alaska , Canabinoides/normas , Relação Dose-Resposta a Droga , Feminino , Humanos , Drogas Ilícitas/sangue , Indóis/normas , Masculino , Detecção do Abuso de Substâncias/métodos , Washington , Adulto Jovem
15.
AAPS PharmSciTech ; 12(2): 573-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21538213

RESUMO

The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P(oct) value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).


Assuntos
Benzimidazóis/farmacocinética , Biofarmácia/métodos , Canabinoides/farmacocinética , Permeabilidade da Membrana Celular/fisiologia , Absorção Intestinal , Absorção Cutânea/fisiologia , Animais , Animais Recém-Nascidos , Benzimidazóis/classificação , Benzimidazóis/normas , Biofarmácia/normas , Canabinoides/classificação , Canabinoides/normas , Permeabilidade da Membrana Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/normas , Absorção Intestinal/efeitos dos fármacos , Absorção Intestinal/fisiologia , Membranas Artificiais , Valor Preditivo dos Testes , Absorção Cutânea/efeitos dos fármacos , Suínos
16.
Phytochemistry ; 71(17-18): 2058-73, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21040939

RESUMO

Cannabis sativa L. is an important medicinal plant. In order to develop cannabis plant material as a medicinal product quality control and clear chemotaxonomic discrimination between varieties is a necessity. Therefore in this study 11 cannabis varieties were grown under the same environmental conditions. Chemical analysis of cannabis plant material used a gas chromatography flame ionization detection method that was validated for quantitative analysis of cannabis monoterpenoids, sesquiterpenoids, and cannabinoids. Quantitative data was analyzed using principal component analysis to determine which compounds are most important in discriminating cannabis varieties. In total 36 compounds were identified and quantified in the 11 varieties. Using principal component analysis each cannabis variety could be chemically discriminated. This methodology is useful for both chemotaxonomic discrimination of cannabis varieties and quality control of plant material.


Assuntos
Canabinoides/normas , Cannabis/química , Preparações Farmacêuticas/normas , Plantas Medicinais/química , Terpenos/provisão & distribuição , Canabinoides/análise , Canabinoides/química , Cannabis/classificação , Cromatografia Gasosa , Estrutura Molecular , Plantas Medicinais/classificação , Padrões de Referência , Terpenos/análise , Terpenos/química
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