Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial

The Lancet, Journal Year: 2018, Volume and Issue: 391(10125), P. 1085 - 1096

Published: Jan. 26, 2018

Language: Английский

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Antioxidative and Anti-Inflammatory Properties of Cannabidiol

Antioxidants, Journal Year: 2019, Volume and Issue: 9(1), P. 21 - 21

Published: Dec. 25, 2019

Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids Cannabis sativa L. CBD non-psychoactive but exerts a number beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry pharmacology CBD, as well various molecular targets, cannabinoid receptors other components endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical clinical studies contributed to our understanding therapeutic potential for many diseases, diseases associated oxidative stress. Here, we review biological effects its synthetic derivatives, focusing on cellular, antioxidant, properties CBD.

Language: Английский

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Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history

Journal of Ethnopharmacology, Journal Year: 2018, Volume and Issue: 227, P. 300 - 315

Published: Sept. 8, 2018

Language: Английский

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The pharmacokinetics and the pharmacodynamics of cannabinoids

British Journal of Clinical Pharmacology, Journal Year: 2018, Volume and Issue: 84(11), P. 2477 - 2482

Published: July 12, 2018

There is increasing interest in the use of cannabinoids for disease and symptom management, but limited information available regarding their pharmacokinetics pharmacodynamics to guide prescribers. Cannabis medicines contain a wide variety chemical compounds, including delta-9-tetrahydrocannabinol (THC), which psychoactive, nonpsychoactive cannabidiol (CBD). associated with both pathological behavioural toxicity and, accordingly, contraindicated context significant psychiatric, cardiovascular, renal or hepatic illness. The effects observed depend on formulation route administration, should be tailored individual patient requirements. As THC CBD are hepatically metabolized, potential exists pharmacokinetic drug interactions via inhibition induction enzymes transporters. An important example CBD-mediated clobazam metabolism. Pharmacodynamic may occur if cannabis administered other central nervous system depressant drugs, cardiac additive hypertension tachycardia sympathomimetic agents. More vulnerable populations, such as older patients, benefit from symptomatic palliative benefits at increased risk adverse effects. availability applicable pharmacodynamic highlights need initiate prescribing using 'start low go slow' approach, carefully observing desired Further clinical studies actual populations whom considered needed, derive better understanding these drugs enhance safe optimal prescribing.

Language: Английский

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An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies

Cannabis and Cannabinoid Research, Journal Year: 2017, Volume and Issue: 2(1), P. 139 - 154

Published: Jan. 1, 2017

Introduction: This literature survey aims to extend the comprehensive performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating literature, this article focuses clinical studies CBD potential interactions with other drugs. Results: In general, often described favorable profile of humans was confirmed extended reviewed research. The majority were for treatment epilepsy psychotic disorders. Here, most commonly reported effects tiredness, diarrhea, changes appetite/weight. comparison drugs, used these medical conditions, has a better effect profile. could improve patients' compliance adherence treatment. is as adjunct therapy. Therefore, more research warranted action hepatic enzymes, drug transporters, drugs see if mainly leads positive or negative effects, example, reducing needed clobazam doses therefore clobazam's Conclusion: review also illustrates that some important toxicological parameters are yet be studied, an hormones. Additionally, trials greater number participants longer chronic administration still lacking.

Language: Английский

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Cannabidiol, neuroprotection and neuropsychiatric disorders

Pharmacological Research, Journal Year: 2016, Volume and Issue: 112, P. 119 - 127

Published: Feb. 1, 2016

Language: Английский

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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects

CNS Drugs, Journal Year: 2018, Volume and Issue: 32(11), P. 1053 - 1067

Published: Oct. 30, 2018

A formal single ascending and multiple dose pharmacokinetic (PK) trial of cannabidiol (CBD) oral solution was required to determine the safety tolerability CBD, maximum tolerated dose, examine effect food on CBD PK parameters. This assessed safety, in healthy adult volunteers, as well The study consisted three arms: (1500, 3000, 4500 or 6000 mg [n = 6 per group]/placebo 8; 2 group]), (750 1500 9 6; 3 group] twice daily), (1500 12]). All subjects completed all arms were analyzed planned. generally tolerated. Diarrhea, nausea, headache, somnolence most common adverse events (AEs) across arms, with an increased incidence some gastrointestinal nervous system disorder AEs (most notably diarrhea headache) apparent taking compared placebo. mild moderate severity; none severe serious. There no deaths discontinuations trial. After doses, appeared rapidly plasma; time plasma concentration (tmax) approximately 4–5 h. major circulating metabolite 7-carboxy-CBD, then parent 7-hydroxy-CBD (active metabolite), 6-hydroxy-CBD (a relatively minor metabolite). Plasma exposure [maximum (Cmax) area under concentration-time curve from zero t (AUCt)] a less than dose-proportional manner (Cmax slope 0.73; AUCt 0.64). Oral clearance high (1111–1909 L/h) volume distribution large (20,963–42,849 L). reached steady state after days, accumulation (1.8- 2.6-fold) 750 daily. 7 twofold increase resulted 1.6- 1.9-fold increases geometric mean Cmax over dosing interval (AUCτ), respectively. elimination multiphasic; terminal half-life 60 h daily; effective estimates ranged 10 17 541.2 ng/mL AUCτ 3236 ng·h/mL high-fat meal AUCt) by 4.85- 4.2-fold, respectively; there tmax half-life. Most profile support twice-daily administration CBD.

Language: Английский

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Review of the Endocannabinoid System

Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Journal Year: 2020, Volume and Issue: 6(6), P. 607 - 615

Published: Aug. 1, 2020

Language: Английский

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Interactions between cannabidiol and commonly used antiepileptic drugs

Epilepsia, Journal Year: 2017, Volume and Issue: 58(9), P. 1586 - 1592

Published: Aug. 6, 2017

Summary Objective To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol ( CBD ; Epidiolex) and commonly used antiepileptic drugs AED s) through an open‐label safety study. Serum levels were monitored to s. Methods In 39 adults 42 children, dose was started at 5 mg/kg/day increased every 2 weeks by up a maximum 50 mg/kg/day. obtained baseline prior initiation most study visits. doses adjusted if it determined that clinical symptom or laboratory result related interaction. The Mixed Procedure determine there significant change in serum level each 19 s with increasing dose. seen initial analysis plotted for mean over time. Subanalyses performed frequency sedation participants N ‐desmethylclobazam level, aspartate aminotransferase (AST) alanine (ALT) different taking concomitant valproate. Results Increases topiramate, rufinamide, decrease clobazam (all p < 0.01) zonisamide (p = 0.02) eslicarbazepine 0.04) adults. Except desmethylclobazam, all noted changes within accepted therapeutic range. Sedation more frequent higher 0.02), AST / ALT significantly valproate 0.01). Significance Significantly changed clobazam, zonisamide, seen. Abnormal liver function test results This emphasizes importance monitoring LFT during treatment .

Language: Английский

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Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy

Cannabis and Cannabinoid Research, Journal Year: 2016, Volume and Issue: 1(1), P. 90 - 101

Published: March 23, 2016

Cannabidiol (CBD), the main nonpsychoactive constituent of Cannabis sativa, has shown a wide range therapeutically promising pharmacological effects either as sole drug or in combination with other drugs adjunctive therapy. However, targets involved therapeutic CBD appear to be elusive. Furthermore, scarce information is available on biological activity its human metabolites which, when formed pharmacologically relevant concentration, might contribute even account for observed effects. The present overview summarizes our current knowledge pharmacokinetics and metabolic fate humans, reviews studies vitro vivo, discusses drug-drug interactions. To facilitate further research area, reported syntheses are also catalogued.

Language: Английский

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