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1.
Am J Public Health ; 110(S3): S294-S299, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33001729

RESUMEN

Objectives. To use crowdfunding campaigns to better understand how cannabidiol (CBD) is represented (and misrepresented) as cancer-related care.Methods. We analyzed CBD-related crowdfunding campaigns (n = 155) created between January 2017 and May 2019 in multiple countries on GoFundme.com.Results. More than 81.9% of campaigns fundraised CBD for curative or life-prolonging reasons, and 25.2% fundraised for pain management.Conclusions. Most campaigns seeking funds for CBD for cancer-related care on GoFundMe are for curative or life-prolonging purposes and present CBD definitively as an effective treatment option. In general, campaigners supported their funding requests with anecdotal claims of efficacy and referenced sources of information that were either not evidence-based or that misrepresented existing evidence.Public Health Implications. Misinformation around CBD for cancer is widespread on medical crowdfunding campaigns. Given the potential adverse impact, crowdfunding platforms, like GoFundMe, must take steps to address their role in enabling and spreading this misinformation.


Asunto(s)
Cannabidiol/administración & dosificación , Comunicación , Colaboración de las Masas/tendencias , Financiación Personal , Neoplasias/terapia , Decepción , Salud Global , Humanos , Neoplasias/mortalidad
2.
J Med Internet Res ; 22(10): e21743, 2020 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-33001829

RESUMEN

BACKGROUND: The COVID-19 outbreak was designated a global pandemic on March 11, 2020. The relationship between vaping and contracting COVID-19 is unclear, and information on the internet is conflicting. There is some scientific evidence that vaping cannabidiol (CBD), an active ingredient in cannabis that is obtained from the hemp plant, or other substances is associated with more severe manifestations of COVID-19. However, there is also inaccurate information that vaping can aid COVID-19 treatment, as well as expert opinion that CBD, possibly administered through vaping, can mitigate COVID-19 symptoms. Thus, it is necessary to study the spread of inaccurate information to better understand how to promote scientific knowledge and curb inaccurate information, which is critical to the health of vapers. Inaccurate information about vaping and COVID-19 may affect COVID-19 treatment outcomes. OBJECTIVE: Using structural topic modeling, we aimed to map temporal trends in the web-based vaping narrative (a large data set comprising web-based vaping chatter from several sources) to indicate how the narrative changed from before to during the COVID-19 pandemic. METHODS: We obtained data using a textual query that scanned a data pool of approximately 200,000 different domains (4,027,172 documents and 361,100,284 words) such as public internet forums, blogs, and social media, from August 1, 2019, to April 21, 2020. We then used structural topic modeling to understand changes in word prevalence and semantic structures within topics around vaping before and after December 31, 2019, when COVID-19 was reported to the World Health Organization. RESULTS: Broadly, the web-based vaping narrative can be organized into the following groups or archetypes: harms from vaping; Vaping Regulation; Vaping as Harm Reduction or Treatment; and Vaping Lifestyle. Three archetypes were observed prior to the emergence of COVID-19; however, four archetypes were identified post-COVID-19 (Vaping as Harm Reduction or Treatment was the additional archetype). A topic related to CBD product preference emerged after COVID-19 was first reported, which may be related to the use of CBD by vapers as a COVID-19 treatment. CONCLUSIONS: Our main finding is the emergence of a vape-administered CBD treatment narrative around COVID-19 when comparing the web-based vaping narratives before and during the COVID-19 pandemic. These results are key to understanding how vapers respond to inaccurate information about COVID-19, optimizing treatment of vapers who contract COVID-19, and possibly minimizing instances of inaccurate information. The findings have implications for the management of COVID-19 among vapers and the monitoring of web-based content pertinent to tobacco to develop targeted interventions to manage COVID-19 among vapers.


Asunto(s)
Cannabidiol/administración & dosificación , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/etiología , Internet/estadística & datos numéricos , Neumonía Viral/epidemiología , Neumonía Viral/etiología , Vapeo/efectos adversos , Vapeo/epidemiología , Cannabidiol/efectos adversos , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/terapia , Humanos , Pandemias , Neumonía Viral/terapia , Fumadores/psicología , Fumadores/estadística & datos numéricos , Medios de Comunicación Sociales , Productos de Tabaco
3.
Farm. hosp ; 44(5): 222-229, sept.-oct. 2020. graf, tab
Artículo en Español | IBECS | ID: ibc-195149

RESUMEN

OBJETIVO: El objetivo del presente trabajo es brindar una revisión sistemática y actualizada acerca de la farmacología de cannabidiol, con especial énfasis en la farmacocinética, eventos adversos e interacciones, vinculada al uso de este fármaco en epilepsias refractarias. MÉTODO: Se realizó una revisión de los trabajos publicados y relaciona-dos con la farmacocinética y los eventos adversos e interacciones farmacológicas de cannabidiol utilizado para el tratamiento de las epilepsias refractarias mediante una búsqueda en PubMed y LILACS. RESULTADOS: Los estudios originales que describen la farmacocinética de cannabidiol de manera exhaustiva son limitados aunque informativos. La absorción de cannabidiol es rápida y se incrementa la biodisponibilidad por la ingesta conjunta de comidas ricas en grasas. El cannabidiol presenta farmacocinética lineal hasta dosis de 3.000 mg/día y se acumula por la administración continua. La semivida de eliminación se referencia entre 14 y 60 horas dependiendo de los tiempos de toma de muestra del estudio farmacocinético y no se descartan modificaciones en la eliminación por la administración en dosis múltiples. De las interacciones farmacológicas entre cannabidiol con otros fármacos antiepilépticos referenciadas hasta el momento, aquella con clobazam es la que presenta mayor evidencia científica. Los eventos adversos más frecuentes asociados al uso de cannabidiol fueron de gravedad leve o moderada e incluyeron somnolencia, principalmente por el uso conjunto de clobazam, y alteraciones gastrointestinales. Se evidenciaron asimismo anormalidades en la función hepática concomitantes con el uso de ácido valproico. CONCLUSIONES: Ante la creciente demanda de la utilización de cannabidiol en epilepsias refractarias, es fundamental el conocimiento de su farmacología por parte del equipo de salud. En especial, el farmacéutico clínico juega un papel primordial en la monitorización de su seguridad y eficacia. Esto permite la optimización del tratamiento clínico del cannabidiol administrado conjuntamente con otros fármacos antiepilépticos de mayor uso, lo que conduce a maximizar la actividad farmacológica y minimizar la aparición de eventos adversos al igual que de interacciones farmacológicas. El seguimiento clínico del paciente resulta fundamental para evitar la discontinuación del tratamiento o exacerbación de eventos adversos que afecten la calidad de vida del paciente


OBJECTIVE: The aim of this article is to provide a systematic and updated review on the pharmacology of cannabidiol in the context of refractory epilepsy, with special emphasis on its pharmacokinetics, adverse drug reactions and drug-drug interactions. METHOD: A review of the literature related to cannabidiol pharmacokinetics, adverse drug reactions and drug-drug interactions was carried out in the context of refractory epilepsy, through a search in PubMed and LILACS. RESULTS: Original studies that exhaustively describe the pharmacokinetics of cannabidiol are limited but informative. Cannabidiol is rapidly absorbed and its bioavailability increases when administered with high fat meals. Cannabidiol exhibits a linear pharmacokinetic profile for doses up to 3,000 mg/day and accumulates after multiple administrations. Elimination half-life has been reported between 14 h and 60 h depending on the sampling times of each study; changes in cannabidiol elimination due to continuous administration cannot be discarded. Of all reported drug-drug interactions with anticonvulsants or other co-administered drugs in patients with epilepsy, the strongest evidence is provided with clobazam. The most frequent cannabidiol-related adverse drug reactions were low to moderate and included somnolence, mainly related to concomitant administration of clobazam, and gastrointestinal alterations. Also, liver function abnormalities were reported during the use of cannabidiol and valproic acid. CONCLUSIONS: Given the increased use of cannabidiol in refractory epilepsy, a comprehensive understanding of its pharmacological profile is essential for the clinical team. Specifically, clinical pharmacists play an important role in monitoring cannabidiol's safety and efficacy. This approach leads to treatment optimization, allowing to maximizing the pharmacological activity and minimizing the occurrence of adverse events as well as drug-to-drug interactions. Clinical follow-up is essential to avoid discontinuation of treatment or exacerbation of adverse events, which may impair the patients' quality of life


Asunto(s)
Humanos , Animales , Epilepsia Refractaria/tratamiento farmacológico , Cannabidiol/farmacocinética , Cannabidiol/efectos adversos , Cannabidiol/administración & dosificación , Clobazam/administración & dosificación , Calidad de Vida
4.
Lancet Psychiatry ; 7(10): 865-874, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32735782

RESUMEN

Background A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design. METHODS: We did a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial at the Clinical Psychopharmacology Unit (University College London, London, UK). We used an adaptive Bayesian dose-finding design to identify efficacious or inefficacious doses at a-priori interim and final analysis stages. Participants meeting cannabis use disorder criteria from DSM-5 were randomly assigned (1:1:1:1) in the first stage of the trial to 4-week treatment with three different doses of oral cannabidiol (200 mg, 400 mg, or 800 mg) or with matched placebo during a cessation attempt by use of a double-blinded block randomisation sequence. All participants received a brief psychological intervention of motivational interviewing. For the second stage of the trial, new participants were randomly assigned to placebo or doses deemed efficacious in the interim analysis. The primary objective was to identify the most efficacious dose of cannabidiol for reducing cannabis use. The primary endpoints were lower urinary 11-nor-9-carboxy-δ-9-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with abstinence from cannabis during treatment, or both, evidenced by posterior probabilities that cannabidiol is better than placebo exceeding 0·9. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000361-36). FINDINGS: Between May 28, 2014, and Aug 12, 2015 (first stage), 48 participants were randomly assigned to placebo (n=12) and to cannabidiol 200 mg (n=12), 400 mg (n=12), and 800 mg (n=12). At interim analysis, cannabidiol 200 mg was eliminated from the trial as an inefficacious dose. Between May 24, 2016, and Jan 12, 2017 (second stage), randomisation continued and an additional 34 participants were allocated (1:1:1) to cannabidiol 400 mg (n=12), cannabidiol 800 mg (n=11), and placebo (n=11). At final analysis, cannabidiol 400 mg and 800 mg exceeded primary endpoint criteria (0·9) for both primary outcomes. For urinary THC-COOH:creatinine ratio, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9995 for cannabidiol 400 mg and 0·9965 for cannabidiol 800 mg. For days with abstinence from cannabis, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9966 for cannabidiol 400 mg and 0·9247 for cannabidiol 800 mg. Compared with placebo, cannabidiol 400 mg decreased THC-COOH:creatinine ratio by -94·21 ng/mL (95% interval estimate -161·83 to -35·56) and increased abstinence from cannabis by 0·48 days per week (0·15 to 0·82). Compared with placebo, cannabidiol 800 mg decreased THC-COOH:creatinine ratio by -72·02 ng/mL (-135·47 to -19·52) and increased abstinence from cannabis by 0·27 days per week (-0·09 to 0·64). Cannabidiol was well tolerated, with no severe adverse events recorded, and 77 (94%) of 82 participants completed treatment. INTERPRETATION: In the first randomised clinical trial of cannabidiol for cannabis use disorder, cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use. FUNDING: Medical Research Council.


Asunto(s)
Cannabidiol/administración & dosificación , Abuso de Marihuana/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias , Adolescente , Adulto , Teorema de Bayes , Cannabidiol/efectos adversos , Método Doble Ciego , Dronabinol/orina , Femenino , Alucinógenos/orina , Humanos , Londres , Masculino , Fumar Marihuana , Resultado del Tratamiento , Adulto Joven
5.
Br J Pharmacol ; 177(21): 4967-4970, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32519753

RESUMEN

Identifying drugs effective in the new coronavirus disease 2019 (COVID-19) is crucial, pending a vaccine against SARS-CoV2. We suggest the hypothesis that cannabidiol (CBD), a non-psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons:- (a) High-cannabidiol Cannabis sativa extracts are able to down-regulate the expression of the two key receptors for SARS-CoV2 in several models of human epithelia, (b) cannabidiol exerts a wide range of immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production responsible for acute lung injury, (c) being a PPARγ agonist, it can display a direct antiviral activity and (d) PPARγ agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by preclinical evidence, will inspire further targeted studies to test cannabidiol as a support drug against the COVID-19 pandemic. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.


Asunto(s)
Cannabidiol/administración & dosificación , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Animales , Betacoronavirus/efectos de los fármacos , Betacoronavirus/aislamiento & purificación , Cannabidiol/aislamiento & purificación , Cannabidiol/farmacología , Cannabis/química , Infecciones por Coronavirus/virología , Progresión de la Enfermedad , Humanos , Pandemias , Extractos Vegetales/química , Extractos Vegetales/farmacología , Neumonía Viral/virología , Índice de Severidad de la Enfermedad
6.
Am J Nurs ; 120(7): 18, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32590581
7.
Pediatrics ; 145(6)2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32444381

RESUMEN

The use of cannabidiol products in pediatric patients is becoming more frequent because of the increased ease of accessibility. This case report illustrates the potential for cannabidiol to interact with stable medication regimens. A 13-year-old girl with metastatic cancer and chronic pain presented with increased sleepiness and fatigue. She had been started on 7.5 mg of methadone by mouth twice daily 4 months earlier. Unbeknownst to her physicians, her parents had commenced her on cannabidiol and subsequently increased the dose leading up to her presentation, thinking it would result in tumor shrinkage. The initial serum methadone level was 271 ng/mL, which decreased to 125 ng/mL 14 days after discontinuing cannabidiol. The reduced serum methadone level coincided with improved sleepiness and fatigue. Cannabidiol inhibits CYP3A4 and CYP2C19, both of which are involved in the metabolism of methadone. Pediatricians should be aware of this potential interaction and inquire if their patients are receiving cannabidiol.


Asunto(s)
Analgésicos Opioides/sangre , Dolor en Cáncer/sangre , Dolor en Cáncer/tratamiento farmacológico , Cannabidiol/sangre , Metadona/sangre , Adolescente , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Cannabidiol/administración & dosificación , Cannabidiol/efectos adversos , Interacciones Farmacológicas/fisiología , Quimioterapia Combinada/métodos , Fatiga/sangre , Fatiga/inducido químicamente , Femenino , Humanos , Metadona/administración & dosificación , Metadona/efectos adversos
8.
Epilepsia ; 61(6): 1090-1098, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32452532

RESUMEN

OBJECTIVE: To evaluate the potential impact of concomitant clobazam (CLB) use on the efficacy of cannabidiol (CBD) treatment in patients with Dravet syndrome and Lennox-Gastaut syndrome using meta-analytical techniques. METHODS: We searched for randomized, placebo-controlled, single- or double-blinded trials. The proportion of patients who achieved ≥50% reduction from baseline in seizure frequency during the treatment period was assessed according to CLB status. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated. RESULTS: Four trials were included and enrolled 714 participants, 429 for the add-on CBD group and 285 for the add-on placebo group. Among CBD-treated patients, 240 (55.9%) were taking concomitant CLB (CLB-On) and 189 (44.1%) were not taking concomitant CLB (CLB-Off); in placebo-treated patients, 158 (55.4%) were CLB-On and 127 (44.6%) CLB-Off. The percentages of patients who had at least 50% reduction in seizure frequency during the treatment period were 29.1% in the CBD arm and 15.7% in the placebo group among CLB-Off patients (RR = 1.80, 95% CI = 1.12-2.90, P = .015). Among CBL-On patients, the ≥50% reduction in seizure frequency was found in 52.9% and 27.8% in the CBD and placebo groups, respectively (RR = 1.85, 95% CI = 1.40-2.44, P < .001). SIGNIFICANCE: CBD was associated with a higher rate of seizure response in comparison to placebo when added to the existing antiepileptic regimen both in patients taking and in those not taking concomitant CLB. The lack of randomization for CLB status and the limited sample size need to be considered in the interpretation of the findings.


Asunto(s)
Anticonvulsivantes/administración & dosificación , Cannabidiol/administración & dosificación , Clobazam/administración & dosificación , Convulsiones/tratamiento farmacológico , Anticonvulsivantes/sangre , Cannabidiol/sangre , Clobazam/sangre , Quimioterapia Combinada , Epilepsias Mioclónicas/sangre , Epilepsias Mioclónicas/tratamiento farmacológico , Humanos , Síndrome de Lennox Gastaut/sangre , Síndrome de Lennox Gastaut/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Convulsiones/sangre , Resultado del Tratamiento
9.
Epilepsia ; 61(6): 1082-1089, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32452568

RESUMEN

Four pivotal randomized placebo-controlled trials have demonstrated that adjunctive therapy with cannabidiol (CBD) improves seizure control in patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS). Between 47% and 68% of patients allocated to CBD treatment in these trials were receiving clobazam (CLB), which shows complex interactions with CBD resulting, in particular, in a 3.4- to 5-fold increase in plasma concentration of the active metabolite norclobazam. This raises concern as to the role played by these interactions in determining the reduction in seizure frequency in CBD-treated patients, and the question of whether CBD per se has clinically evident antiseizure effects. We appraised available evidence on the clinical consequences of the CBD-CLB interaction, focusing on subgroup analyses of seizure outcomes in patients on and off CLB comedication in the pivotal CBD trials, as provided by the European Medicines Agency Public Assessment Report. Evaluation of the results of individual trials clearly showed that improvement in seizure control over placebo was greater when CBD was added on to CLB than when it was added on to other medications. However, seizure control was also improved in patients off CLB, and despite the small sample size the difference vs placebo was statistically significant for the 10 mg/kg/d dose in one of the two LGS trials. Stronger evidence for an antiseizure effect of CBD independent of an interaction with CLB emerges from meta-analyses of seizure outcomes in the pooled population of LGS and DS patients not receiving CLB comedication. Although these results need to be interpreted taking into account methodological limitations, they provide the best clinical evidence to date that CBD exerts therapeutic effects in patients with epilepsy that are independent of its interaction with CLB. Greater antiseizure effects, and a greater burden of adverse effects, are observed when CBD is combined with CLB.


Asunto(s)
Anticonvulsivantes/administración & dosificación , Cannabidiol/administración & dosificación , Clobazam/administración & dosificación , Medicina Basada en la Evidencia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Convulsiones/tratamiento farmacológico , Anticonvulsivantes/sangre , Cannabidiol/sangre , Clobazam/sangre , Interacciones Farmacológicas/fisiología , Quimioterapia Combinada , Epilepsias Mioclónicas/sangre , Epilepsias Mioclónicas/tratamiento farmacológico , Humanos , Síndrome de Lennox Gastaut/sangre , Síndrome de Lennox Gastaut/tratamiento farmacológico , Convulsiones/sangre
10.
Clin Drug Investig ; 40(4): 319-326, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32130684

RESUMEN

INTRODUCTION: Multiple sclerosis (MS) is a highly symptomatic disease, with a wide range of disabilities affecting many bodily functions, even in younger persons with a short disease history. The availability of a cannabinoid oromucosal spray (Sativex) for the management of treatment-resistant MS spasticity has provided a new opportunity for many patients. OBJECTIVE: Our study aimed to assess the cost effectiveness of Sativex in Italian patients with treatment-resistant MS spasticity. The analysis was based on the real-world data of a large registry of Italian patients. METHODS: A cost-utility analysis was conducted using data collected prospectively from an electronic registry of all patients who began to use Sativex for MS-resistant spasticity between January 2014 and February 2015 in 30 specialized MS units across Italy and were followed up for ≤ 6 months. Data on drug consumption and spasticity/utility were used to estimate the incremental cost-effectiveness ratio (ICER) of Sativex, as compared with no intervention. No costs or spasticity/utility changes were assumed for no treatment intervention. The ICER was expressed as quality-adjusted life-years (QALYs) gained, using the Italian NHS perspective and a 6-month time horizon. RESULTS: Sativex effectiveness and consumption was estimated analyzing data of 1350 patients from the registry. These patients reported a mean (SD) utility increment of 0.087 (0.069) after 1 month of treatment, 0.118 (0.073) after 3 months' treatment and 0.127 (0.080) after 6 months' treatment. The 6-month cost of treating the entire population with Sativex was €1,361,266, with a €1008 cost and 0.0284 QALYs gained per patient. The estimated ICER was €35,516 per QALY gained, with little variability around the central estimate of cost-effectiveness, as shown by the cost-effectiveness acceptability curve. CONCLUSION: The use of Sativex could improve the quality of life of patients with a reasonable incremental cost resulting as a cost-effective option for patients with MS-resistant spasticity. These results could help clinicians and decision makers to develop improved management strategies for spasticity in patients with MS, optimizing the use of available resources.


Asunto(s)
Cannabidiol/administración & dosificación , Dronabinol/administración & dosificación , Esclerosis Múltiple/tratamiento farmacológico , Espasticidad Muscular/tratamiento farmacológico , Adulto , Análisis Costo-Beneficio , Combinación de Medicamentos , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida
11.
Pneumologie ; 74(2): 77-87, 2020 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-32016924

RESUMEN

Beginning in April of 2019, the US saw > 2,000 cases of hospitalized, often young, patients with severe acute lung injury, of which over 40 died, and the only existing connection between patients was their use of electronic cigarettes (e-cigarettes). The acronym EVALI ("e-cigarette, or vaping, product use associated lung injury") has since been established for the condition. This review article is intended to provide an overview of recent, mainly US literature on EVALI, including the case definition, epidemiology, clinical presentation, typical disease progression, as well as potential triggers. Ancillary to this, the review further provides a general overview of the basic function of e-cigarettes, the ingredients of the liquids used in these (e-liquids), as well as a brief description of the associated potential inhalation risks.


Asunto(s)
Lesión Pulmonar Aguda/inducido químicamente , Dronabinol/efectos adversos , Sistemas Electrónicos de Liberación de Nicotina , Vapeo/efectos adversos , Lesión Pulmonar Aguda/epidemiología , Cannabidiol/administración & dosificación , Cannabidiol/efectos adversos , Brotes de Enfermedades , Dronabinol/administración & dosificación , Humanos , Nicotina/administración & dosificación , Nicotina/efectos adversos , Factores de Riesgo
12.
Epileptic Disord ; 22(1): 1-14, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-32096470

RESUMEN

The growing interest in cannabidiol (CBD), specifically a pure form of CBD, as a treatment for epilepsy, among other conditions, is reflected in recent changes in legislation in some countries. Although there has been much speculation about the therapeutic value of cannabis-based products as an anti-seizure treatment for some time, it is only within the last two years that Class I evidence has been available for a pure form of CBD, based on placebo-controlled RCTs for patients with Lennox-Gastaut syndrome and Dravet syndrome. However, just as we are beginning to understand the significance of CBD as a treatment for epilepsy, in recent years, a broad spectrum of products advertised to contain CBD has emerged on the market. The effects of these products are fundamentally dependent on the purity, preparation, and concentration of CBD and other components, and consensus and standardisation are severely lacking regarding their preparation, composition, usage and effectiveness. This review aims to provide information to neurologists and epileptologists on the therapeutic value of CBD products, principally a purified form, in routine practice for patients with intractable epilepsy.


Asunto(s)
Cannabidiol/farmacología , Moduladores de Receptores de Cannabinoides/farmacología , Epilepsia Refractaria/tratamiento farmacológico , Epilepsias Mioclónicas/tratamiento farmacológico , Síndrome de Lennox Gastaut/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Cannabidiol/administración & dosificación , Cannabidiol/normas , Moduladores de Receptores de Cannabinoides/administración & dosificación , Moduladores de Receptores de Cannabinoides/normas , Humanos
13.
Psychopharmacology (Berl) ; 237(4): 1121-1130, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31915861

RESUMEN

RATIONALE: Stress is a risk factor for psychosis and treatments which mitigate its harmful effects are needed. Cannabidiol (CBD) has antipsychotic and anxiolytic effects. OBJECTIVES: We investigated whether CBD would normalise the neuroendocrine and anxiety responses to stress in clinical high risk for psychosis (CHR) patients. METHODS: Thirty-two CHR patients and 26 healthy controls (HC) took part in the Trier Social Stress Test (TSST) and their serum cortisol, anxiety and stress associated with public speaking were estimated. Half of the CHR participants were on 600 mg/day of CBD (CHR-CBD) and half were on placebo (CHR-P) for 1 week. RESULTS: One-way analysis of variance (ANOVA) revealed a significant effect of group (HC, CHR-P, CHR-CBD (p = .005) on cortisol reactivity as well as a significant (p = .003) linear decrease. The change in cortisol associated with experimental stress exposure was greatest in HC controls and least in CHR-P patients, with CHR-CBD patients exhibiting an intermediate response. Planned contrasts revealed that the cortisol reactivity was significantly different in HC compared with CHR-P (p = .003), and in HC compared with CHR-CBD (p = .014), but was not different between CHR-P and CHR-CBD (p = .70). Across the participant groups (CHR-P, CHR-CBD and HC), changes in anxiety and experience of public speaking stress (all p's < .02) were greatest in the CHR-P and least in the HC, with CHR-CBD participants demonstrating an intermediate level of change. CONCLUSIONS: Our findings show that it is worthwhile to design further well powered studies which investigate whether CBD may be used to affect cortisol response in clinical high risk for psychosis patients and any effect this may have on symptoms.


Asunto(s)
Ansiedad/tratamiento farmacológico , Cannabidiol/administración & dosificación , Trastornos Psicóticos/tratamiento farmacológico , Conducta Social , Estrés Psicológico/tratamiento farmacológico , Adolescente , Adulto , Ansiolíticos/administración & dosificación , Antipsicóticos/administración & dosificación , Ansiedad/sangre , Ansiedad/psicología , Método Doble Ciego , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Trastornos Psicóticos/sangre , Trastornos Psicóticos/psicología , Factores de Riesgo , Habla/efectos de los fármacos , Habla/fisiología , Estrés Psicológico/sangre , Estrés Psicológico/psicología , Resultado del Tratamiento , Adulto Joven
14.
Psychopharmacology (Berl) ; 237(3): 901-914, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31897571

RESUMEN

RATIONALE: This study evaluated the potential of combined cannabis constituents to reduce nausea. OBJECTIVES: Using the lithium chloride (LiCl)-induced conditioned gaping model of nausea in male rats, we aimed to: 1) Determine effective anti-nausea doses of cannabidiol (CBD) 2) Determine effectiveness and the mechanism of action of combined subthreshold doses of CBD and Δ9-tetrahydrocannabinol (THC) 3) Determine effective doses of synthetic cannabidiolic acid (CBDA) 4) Determine effective doses of synthetic tetrahydrocannabinolic acid (THCA) 5) Determine the mechanism of action for THCA 6) Determine effectiveness and the mechanism of action of combined subthreshold doses of CBDA and THCA RESULTS: CBD (0.5-5 mg/kg, intraperitoneal [i.p.]) reduces LiCl-induced conditioned gaping (but 0.1, 20, 40 mg/kg are ineffective). Combined subthreshold doses of CBD (0.1 mg/kg, i.p.) and THC (0.1 mg/kg, i.p.) produce suppression of conditioned gaping, and this effect is blocked by administration of either WAY100635 (a serotonin 1A [5-HT1A]) receptor antagonist or SR141716 (SR; a CB1 receptor antagonist). THCA (0.01 mg/kg, i.p.) reduces conditioned gaping and administration of MK886 (a peroxisome proliferator-activated receptor alpha [PPARα] antagonist) blocked THCA's anti-nausea effect. Combined subthreshold doses of CBDA (0.00001 mg/kg, i.p.) and THCA (0.001 mg/kg, i.p.) produce suppression of conditioned gaping, and this effect is blocked by administration of WAY100635 or MK886. CONCLUSION: Combinations of very low doses of CBD + THC or CBDA + THCA robustly reduce LiCl-induced conditioned gaping. Clinical trials are necessary to determine the efficacy of using single or combined cannabinoids as adjunct treatments with existing anti-emetic regimens to manage chemotherapy-induced nausea.


Asunto(s)
Antieméticos/administración & dosificación , Cannabidiol/administración & dosificación , Cannabinoides/administración & dosificación , Dronabinol/administración & dosificación , Náusea/tratamiento farmacológico , Animales , Agonistas de Receptores de Cannabinoides/administración & dosificación , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Masculino , Náusea/fisiopatología , Ratas , Ratas Sprague-Dawley
15.
Psychopharmacology (Berl) ; 237(4): 1063-1079, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31919563

RESUMEN

RATIONALE: The behavioural effects elicited by chemical constituents of Cannabis sativa, such as cannabidiol (CBD), on the ventromedial hypothalamus (VMH) are not well understood. There is evidence that VMH neurons play a relevant role in the modulation of unconditioned fear-related defensive behavioural reactions displayed by laboratory animals. OBJECTIVES: This study was designed to explore the specific pattern of distribution of the CB1 receptors in the VMH and to investigate the role played by this cannabinoid receptor in the effect of CBD on the control of defensive behaviours and unconditioned fear-induced antinociception. METHODS: A panic attack-like state was triggered in Wistar rats by intra-VMH microinjections of N-methyl-D-aspartate (NMDA). One of three different doses of CBD was microinjected into the VMH prior to local administration of NMDA. In addition, the most effective dose of CBD was used after pre-treatment with the CB1 receptor selective antagonist AM251, followed by NMDA microinjections in the VMH. RESULTS: The morphological procedures demonstrated distribution of labelled CB1 receptors on neuronal perikarya situated in dorsomedial, central and ventrolateral divisions of the VMH. The neuropharmacological approaches showed that both panic attack-like behaviours and unconditioned fear-induced antinociception decreased after intra-hypothalamic microinjections of CBD at the highest dose (100 nmol). These effects, however, were blocked by the administration of the CB1 receptor antagonist AM251 (100 pmol) in the VMH. CONCLUSION: These findings suggest that CBD causes panicolytic-like effects and reduces unconditioned fear-induced antinociception when administered in the VMH, and these effects are mediated by the CB1 receptor-endocannabinoid signalling mechanism in VMH.


Asunto(s)
Cannabidiol/toxicidad , Miedo/fisiología , Dimensión del Dolor/métodos , Trastorno de Pánico/metabolismo , Receptor Cannabinoide CB1/metabolismo , Núcleo Hipotalámico Ventromedial/metabolismo , Animales , Cannabidiol/administración & dosificación , Miedo/efectos de los fármacos , Miedo/psicología , Inyecciones Intraventriculares , Masculino , N-Metilaspartato/administración & dosificación , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/psicología , Trastorno de Pánico/inducido químicamente , Piperidinas/administración & dosificación , Pirazoles/administración & dosificación , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/antagonistas & inhibidores , Núcleo Hipotalámico Ventromedial/efectos de los fármacos
16.
Dig Dis Sci ; 65(1): 322-328, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31363952

RESUMEN

BACKGROUND AND AIMS: Utilization and safety of cannabidiol (CBD) in patients with autoimmune hepatitis (AIH) are currently unknown. We aimed to identify the frequency of CBD use, impact on symptoms, and safety profile. METHODS: An invitation to complete a CBD-specific questionnaire was posted every other day to well-established autoimmune hepatitis Facebook communities (combined membership of 2600 individuals) during a 10-day study period. Age ≥ 18 years and an AIH diagnosis by a physician were the eligibility criteria for participation in the survey. RESULTS: In total, 371 AIH patients (median age 49 years, 32% reported advanced fibrosis) completed the questionnaire. Respondents were 91% women, 89% Caucasian, and 89% from North America. Ninety-three (25%) respondents were ever CBD users, with 55 of them (15% of the survey responders) identified as current users. Among ever users, 45.7% reported their treating doctors were aware of their CBD use. The most common reason cited for CBD use was pain (68%), poor sleep (62%), and fatigue (38%). Most respondents using CBD for these symptoms reported a significant improvement in pain (82%), sleep (87%), and fatigue (61%). In ever CBD users, 17.3% were able to stop a prescription medication because of CBD use: pain medication (47%), immunosuppression (24%), and sleep aids (12%). Side effects attributed to CBD use were reported in 3% of CBD users, yet there were no reported emergency department visits or hospitalizations. CONCLUSION: CBD use was not uncommon in patients with AIH, and its use was associated with reports of improvement in extrahepatic symptoms.


Asunto(s)
Cannabidiol/administración & dosificación , Hepatitis Autoinmune/tratamiento farmacológico , Automedicación , Adulto , Cannabidiol/efectos adversos , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Medición de Riesgo , Automedicación/efectos adversos , Medios de Comunicación Sociales , Factores de Tiempo , Resultado del Tratamiento
17.
J Neurol ; 267(2): 415-421, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31655890

RESUMEN

BACKGROUND: The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory. Some patients anecdotally report symptoms' relief through consumption of cannabis. METHODS: A combination of cannabidiol and tetrahydrocannabinol (CBD/THC) was prescribed as compassionate use to six patients (four patients with myotonic dystrophy types 1 and 2, and 2 patients with CLCN1-myotonia) with therapy-resistant myotonia and myalgia. CBD/THC oil was administered on a low dose in the first 2 weeks and adjusted to a higher dose in the following 2 weeks. Myotonia behaviour scale (MBS), hand-opening time, visual analogue scales (VAS) for myalgia and myotonia, and fatigue and daytime sleepiness severity scale (FSS, ESS) were performed weekly to monitor treatment response. RESULTS: All patients reported an improvement of myotonia especially in weeks 3 and 4 of treatment: MBS improved of at least 2 points in all patients, the hand-opening time variously improved in 5 out of 6 patients. Chronic myalgia was reported by both DM2 patients at baseline, one of them experienced a significant improvement of myalgia under treatment. Some gastrointestinal complaints, as abdominal pain and diarrhoea, improved in 3 patients; however, 4 out of 6 patients reported new-onset constipation. No other relevant side effect was noticed. CONCLUSIONS: These first empirical results suggest a potentially beneficial role of CBD/THC in alleviating myotonia and should encourage further research in this field including a randomized-controlled trial on larger cohorts.


Asunto(s)
Cannabidiol/farmacología , Moduladores de Receptores de Cannabinoides/farmacología , Dronabinol/farmacología , Distrofias Musculares/tratamiento farmacológico , Mialgia/tratamiento farmacológico , Miotonía/tratamiento farmacológico , Adulto , Anciano , Cannabidiol/administración & dosificación , Moduladores de Receptores de Cannabinoides/administración & dosificación , Enfermedad Crónica , Estudios de Cohortes , Ensayos de Uso Compasivo , Dronabinol/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceites , Resultado del Tratamiento
19.
Epilepsy Behav ; 102: 106826, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31816477

RESUMEN

PURPOSE: Limited data suggest that cannabidiol (CBD) may be effective for treatment of refractory infantile spasms (IS). This study was designed to more rigorously evaluate the efficacy and safety of synthetic CBD in the treatment of IS. METHODS: Children six to 36 months of age with IS that failed treatment with both adrenocorticotropic hormone (ACTH) and vigabatrin (VGB) were eligible for enrollment. Children receiving clobazam were excluded. After baseline overnight video-electroencephalography (vEEG) to confirm diagnosis and ascertain hypsarrhythmia, patients were treated with synthetic CBD oral solution (20 mg/kg/day). Overnight video-EEG was repeated after 14 days, and both baseline and repeat video-EEGs were completely de-identified and reviewed in a pairwise fashion by an independent, blinded pediatric electroencephalographer. The primary efficacy endpoint was freedom from spasms and hypsarrhythmia on day 14. RESULTS: Nine patients were enrolled, comprising an older (median age = 23 months) cohort with long-standing IS (median duration = 13 months) and numerous prior treatment failures (median = 6). One patient responded to therapy and eight patients exhibited neither clinical nor electrographic response. CONCLUSIONS: The immediate but temporary response in a single patient suggests that CBD oral solution is not particularly effective in highly refractory cases, but may, nevertheless, be effective in younger patients with shorter durations of IS. Further study, examining both short- and long-term outcomes, is warranted to further evaluate the efficacy and safety of CBD oral solution in the treatment of IS.


Asunto(s)
Anticonvulsivantes/farmacología , Cannabidiol/farmacología , Epilepsia Refractaria/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , Espasmos Infantiles/tratamiento farmacológico , Anticonvulsivantes/administración & dosificación , Cannabidiol/administración & dosificación , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino
20.
Curr Pharm Biotechnol ; 21(5): 390-402, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31793418

RESUMEN

BACKGROUND: Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the treatment of chronic, noncancer pain. The efficacy of a topically delivered cannabidiol (CBD) oil in the management of neuropathic pain was examined in this four-week, randomized and placebocontrolled trial. METHODS: In total, 29 patients with symptomatic peripheral neuropathy were recruited and enrolled. 15 patients were randomized to the CBD group with the treatment product containing 250 mg CBD/3 fl. oz, and 14 patients were randomized to the placebo group. After four weeks, the placebo group was allowed to crossover into the treatment group. The Neuropathic Pain Scale (NPS) was administered biweekly to assess the mean change from baseline to the end of the treatment period. RESULTS: The study population included 62.1% males and 37.9% females with a mean age of 68 years. There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group. No adverse events were reported in this study. CONCLUSION: Our findings demonstrate that the transdermal application of CBD oil can achieve significant improvement in pain and other disturbing sensations in patients with peripheral neuropathy. The treatment product was well tolerated and may provide a more effective alternative compared to other current therapies in the treatment of peripheral neuropathy.


Asunto(s)
Analgésicos no Narcóticos/uso terapéutico , Cannabidiol/uso terapéutico , Portadores de Fármacos/química , Extremidad Inferior/inervación , Neuralgia/tratamiento farmacológico , Aceites/química , Administración Cutánea , Adulto , Anciano , Analgésicos no Narcóticos/administración & dosificación , Cannabidiol/administración & dosificación , Dolor Crónico , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Microglía/metabolismo , Calidad de Vida , Receptor Cannabinoide CB2/metabolismo , Resultado del Tratamiento
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