Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial

The Lancet Neurology, Journal Year: 2015, Volume and Issue: 15(3), P. 270 - 278

Published: Dec. 24, 2015

Language: Английский

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Cannabidiol as a Potential Treatment for Anxiety Disorders

Neurotherapeutics, Journal Year: 2015, Volume and Issue: 12(4), P. 825 - 836

Published: Sept. 4, 2015

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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Molecular Targets of Cannabidiol in Neurological Disorders

Neurotherapeutics, Journal Year: 2015, Volume and Issue: 12(4), P. 699 - 730

Published: Aug. 11, 2015

Language: Английский

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From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

Physiological Reviews, Journal Year: 2016, Volume and Issue: 96(4), P. 1593 - 1659

Published: Sept. 15, 2016

Apart from having been used and misused for at least four millennia for, among others, recreational medicinal purposes, the cannabis plant its most peculiar chemical components, cannabinoids (phytocannabinoids), have merit to led humanity discover one of intriguing pleiotropic endogenous signaling systems, endocannabinoid system (ECS). This review article aims describe critically discuss, in comprehensive possible manner, multifaceted aspects 1) pharmacology potential impact on mammalian physiology all major phytocannabinoids, not only famous Δ 9 -tetrahydrocannabinol, 2) adaptive pro-homeostatic physiological, or maladaptive pathological, roles ECS cells, tissues, organs. In doing so, we respected chronological order milestones millennial route medicinal/recreational beyond, as it is now clear that some early steps this long path, which were originally neglected, are becoming important again. The emerging picture rather complex, but still supports belief more discoveries human physiology, new therapies, might come future knowledge field.

Language: Английский

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Cannabidiol Adverse Effects and Toxicity

Current Neuropharmacology, Journal Year: 2019, Volume and Issue: 17(10), P. 974 - 989

Published: June 3, 2019

Currently, there is a great interest in the potential medical use of cannabidiol (CBD), non-intoxicating cannabinoid. Productive pharmacological research on CBD occurred 1970s and intensified recently with many discoveries about endocannabinoid system. Multiple preclinical clinical studies led to FDA-approval Epidiolex®, purified medicine formulated for oral administration treatment infantile refractory epileptic syndromes, by US Food Drug Administration 2018. The World Health Organization considers rescheduling cannabis cannabinoids. around world expanding diseases that lack scientific evidence drug's efficacy. Preclinical also report adverse effects (AEs) toxicity following intake.Relevant reporting CBD's AEs or were identified from PubMed, Cochrane Central, EMBASE through January 2019. Studies defining beneficial included provide balance estimating risk/benefit.CBD not risk-free. In animals, developmental toxicity, embryo-fetal mortality, central nervous system inhibition neurotoxicity, hepatocellular injuries, spermatogenesis reduction, organ weight alterations, male reproductive hypotension, although at doses higher than recommended human pharmacotherapies. Human epilepsy psychiatric disorders reported CBD-induced drug-drug interactions, hepatic abnormalities, diarrhea, fatigue, vomiting, somnolence.CBD has proven therapeutic efficacy serious conditions such as Dravet Lennox-Gastaut syndromes likely be off label physicians other conditions. However, interactions must taken into consideration clinicians prior recommending off-label CBD.

Language: Английский

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Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort

Brain, Journal Year: 2019, Volume and Issue: 142(8), P. 2303 - 2318

Published: June 12, 2019

Epilepsy is common in early childhood. In this age group it associated with high rates of therapy-resistance, and cognitive, motor, behavioural comorbidity. A large number genes, wide ranging functions, are implicated its aetiology, especially those therapy-resistant seizures. Identifying the more single-gene epilepsies will aid targeting resources, prioritization diagnostic testing development precision therapy. Previous studies genetic epilepsy have not been prospective population-based. Therefore, population-incidence remains unknown. The objective study was to describe incidence phenotypic spectrum most young children, calculate what proportion amenable This a national epidemiological cohort study. All children presenting before 36 months were eligible. Children recurrent prolonged (>10 min) febrile seizures; or afebrile status epilepticus (>30 min); clusters two seizures within 24-h period also Participants recruited from all 20 regional paediatric departments four tertiary children's hospitals Scotland over 3-year period. DNA samples tested on custom-designed 104-gene panel. Detailed clinical information systematically gathered at initial presentation during follow-up. Clinical data reviewed by multidisciplinary team clinicians scientists. pathogenic significance variants assessed accordance guidelines UK Association Genetic Science (ACGS). Of 343 patients who met inclusion criteria, 333 completed testing, 80/333 (24%) had finding. overall estimated annual well-defined population 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9-57.5). PRRT2 an 9970 (10.0/100 5.26-14.8) followed SCN1A: 12 200 (8.26/100 3.93-12.6); KCNQ2: 17 000 (5.89/100 2.24-9.56) SLC2A1: 24 300 (4.13/100 1.07-7.19). Presentation 6 months, focal significantly diagnosis. Single-gene disorders accounted for quarter seizure cohort. recommended identify may benefit treatment should be mainstream practice childhood onset epilepsy.

Language: Английский

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Cannabidiol in Anxiety and Sleep: A Large Case Series

The Permanente Journal, Journal Year: 2019, Volume and Issue: 23(1)

Published: Jan. 4, 2019

Cannabidiol (CBD) is one of many cannabinoid compounds found in cannabis. It does not appear to alter consciousness or trigger a "high." A recent surge scientific publications has preclinical and clinical evidence documenting value for CBD some neuropsychiatric disorders, including epilepsy, anxiety, schizophrenia. Evidence points toward calming effect the central nervous system. Interest as treatment wide range disorders exploded, yet few studies exist psychiatric literature.To determine whether helps improve sleep and/or anxiety population.A large retrospective case series at clinic involving application complaints an adjunct usual treatment. The chart review included monthly documentation quality 103 adult patients.Sleep scores, using validated instruments, baseline after treatment.The final sample consisted 72 adults presenting with primary concerns (n = 47) poor 25). Anxiety scores decreased within first month 57 patients (79.2%) remained during study duration. Sleep improved 48 (66.7%) but fluctuated over time. In this review, was well tolerated all 3 patients.Cannabidiol may hold benefit anxiety-related disorders. Controlled are needed.

Language: Английский

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Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome

Proceedings of the National Academy of Sciences, Journal Year: 2017, Volume and Issue: 114(42), P. 11229 - 11234

Published: Oct. 2, 2017

Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures autistic-like social deficits in a well-validated mouse genetic model Dravet syndrome (DS), severe childhood epilepsy disorder caused by loss-of-function mutations the brain voltage-gated sodium channel NaV1.1. The duration severity thermally induced frequency spontaneous were substantially decreased. Treatment with lower doses CBD also improved interaction DS mice. Phenotypic rescue was associated restoration excitability inhibitory interneurons hippocampal dentate gyrus, an important area for seizure propagation. Reduced granule neurons response to strong depolarizing stimuli observed. beneficial effects on neurotransmission mimicked occluded antagonist GPR55, suggesting therapeutic are mediated through this lipid-activated G protein-coupled receptor. Our results provide critical supporting treatment behaviors linked CBD. We introduce antagonism GPR55 as potential approach illustrating study provides essential needed build sound scientific basis increased

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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