Cannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle, Liver and Adipose Tissue

Nutrients, Journal Year: 2022, Volume and Issue: 14(10), P. 2101 - 2101

Published: May 18, 2022

Oral cannabidiol (CBD) consumption is widespread in North America and Europe, as it has analgesic, neuroprotective antitumor effects. Although oral CBD humans affords beneficial effects epileptic inflammatory states, its pharmacokinetics subsequent uptake into tissue are largely unknown. This study investigated plasma accumulation of gastrocnemius muscle, liver adipose adult rats following gavage. was fed relative to body mass at 0 (control), 30, 115, or 230 mg/Kg/day for 28 days; with 6 males females per dosing group. Pharmacokinetics were assessed on day 1 the group receiving 115 mg/Kg/day. The rise closely related specific pharmacokinetic parameters, levels ~10 ~100 fold greater than muscle. Tissue moderately correlated between liver, but highly feeding resulted several gender-specific effects, including changes pharmacokinetics, relationships parameters differences levels. mammalian tissues potential influence receptor binding metabolism; therefore, present findings may have relevance developing regimens.

Language: Английский

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Cannabidiol‐associated hepatotoxicity: A systematic review and meta‐analysis

Journal of Internal Medicine, Journal Year: 2023, Volume and Issue: 293(6), P. 724 - 752

Published: March 13, 2023

Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over safety. This study aimed to determine the association between use, elevation, and drug-induced injury (DILI).In this systematic review meta-analysis, a search EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov, Medline, medRxiv, Web Science records up February 2022 was conducted. Clinical trials initiating daily treatment with serial measures were included. The proportion DILI independently extracted from published reports. Pooled proportions probability meta-analyses conducted.Cannabidiol use associated an increased elevation (N = 12 trials, n 1229; OR 5.85 95% CI 3.84-8.92, p < 0.001) 4.82 2.46-9.45, compared placebo controls. In participants taking 28 1533), pooled 0.074 (95% 0.0448-0.1212), 0.0296 0.0136-0.0631). High-dose CBD (≥1000 mg/day or ≥20 mg/kg/day) concomitant antiepileptic drug identified as risk factors. No cases reported adults using doses <300 mg/day. severe reported.Cannabidiol-associated meet criteria common adverse events. Clinicians are encouraged screen for monitor function patients at risk.

Language: Английский

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Cannabis Pharmacogenomics: A Path to Personalized Medicine

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(4), P. 3479 - 3514

Published: April 17, 2023

Cannabis and related compounds have created significant research interest as a promising therapy in many disorders. However, the individual therapeutic effects of cannabinoids incidence side are still difficult to determine. Pharmacogenomics may provide answers questions concerns regarding cannabis/cannabinoid treatment help us understand variability responses associated risks. has made meaningful progress identifying genetic variations that play critical role interpatient response cannabis. This review classifies current knowledge pharmacogenomics with medical marijuana can assist improving outcomes cannabinoid minimize adverse cannabis use. Specific examples informing pharmacotherapy path personalized medicine discussed.

Language: Английский

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Natural product-derived therapies for treating drug-resistant epilepsies: From ethnopharmacology to evidence-based medicine

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 317, P. 116740 - 116740

Published: June 12, 2023

Language: Английский

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Multifaceted targets of cannabidiol in epilepsy: Modulating glutamate signaling and beyond

Computers in Biology and Medicine, Journal Year: 2024, Volume and Issue: 179, P. 108898 - 108898

Published: July 23, 2024

Language: Английский

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Long‐term efficacy and safety of cannabidiol in patients with treatment‐resistant epilepsies: Four‐year results from the expanded access program

Epilepsia, Journal Year: 2022, Volume and Issue: 64(3), P. 619 - 629

Published: Dec. 20, 2022

Abstract Objective Cannabidiol (CBD) expanded access program, initiated in 2014, provided add‐on CBD to patients with treatment‐resistant epilepsies (TREs) at 35 US epilepsy centers. Prior publications reported results through December 2016; herein, we present efficacy and safety January 2019. Methods Patients received plant‐derived highly purified (Epidiolex®; 100 mg/ml oral solution), increasing from 2 10 mg/kg/day tolerance or maximum 25–50 dose, depending on the study site. Efficacy endpoints included percentage change baseline median monthly convulsive total seizure frequency ≥50%, ≥75%, 100% responder rates across 12‐week visit windows for up 192 weeks. Adverse events (AEs) were documented each visit. Results Of 892 analysis set, 322 (36%) withdrew; lack of (19%) AEs (7%) most commonly primary reasons withdrawal. Median (range) age was 11.8 years (range = 0–74.5), taking a three 0–10) antiseizure medications (ASMs) baseline; common ASMs clobazam (47%), levetiracetam (34%), valproate (28%). top dose 25 mg/kg/day; exposure duration 694 days. reduction ranged 50%–67% seizures 46%–66% seizures. Convulsive (≥50%, reduction) 51%–59%, 33%–42%, 11%–17% windows, respectively. 88% serious 41%; 8% withdrew because an AE. There 20 deaths during deemed unrelated treatment by investigator. The (≥20% patients) diarrhea (33%), (24%), somnolence (23%). Significance Add‐on associated sustained weeks acceptable profile can be used long‐term TREs.

Language: Английский

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Cannabinoids and endocannabinoids as therapeutics for nervous system disorders: preclinical models and clinical studies

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(4), P. 788 - 799

Published: Aug. 14, 2023

Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body. They have been studied cellular and animal models as well clinical trials for their therapeutic benefits several diseases. Some these include central nervous system (CNS) diseases dysfunctions such forms epilepsy, multiple sclerosis, Parkinson’s disease, pain neuropsychiatric disorders. In addition, endogenously produced cannabinoid lipids, endocannabinoids, critical normal CNS function, if controlled or modified, may represent an additional avenue This review discusses vitro cellular, ex vivo tissue model studies on cannabinoids utility therapeutics pathologies. provides overview use endocannabinoids hold promise disease modifiers agents prevention treatment neurodegenerative neurological

Language: Английский

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Exploring the impact of pharmacogenetics on personalized medicine: A systematic review

Farmacia Hospitalaria, Journal Year: 2024, Volume and Issue: 48(6), P. 299 - 309

Published: Feb. 9, 2024

Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Implementation Consortium) resources like PharmGKB facilitate genotype-based prescribing; organizations the FDA promote testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers diverse populations needed. The aim of this review to analyze recent evidence genotype–drug response relationship examine profile patients influences treatments, areas that need study advance towards a genetic-based precision medicine. A systematic search was conducted PubMed identify articles investigating relationship. strategy included terms "pharmacogenetics", "personalized treatment", "precision medicine", "dose adjustment", "individualizing dosing", "clinical routine", practice." Clinical trials, observational studies, meta-analyses published in English or Spanish between 2013 2023 were included. initial resulted total 136 for analysis. 49 final analysis following 2 investigators. polymorphisms toxicity found drugs opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNFα agents, voriconazole, antidepressants, statins. However, metformin, quetiapine, irinotecan, bisoprolol, anti-VEGF no statistically significant association genotype found. studies analyzed suggest strong correlation variability individual responses, supporting use pharmacogenetics treatment optimization. metformin their remains unclear. More with larger sample sizes, greater ethnic diversity, consideration non-genetic factors are lack standardization methods accessibility challenges field. As conclusion, shows immense potential personalized medicine, required. La farmacogenética evalúa cómo variantes genéticas influyen en la respuesta medicamentos. En actualidad las pruebas han avanzado, son más asequibles y su integración se respalda con evidencia clínica sólida. Guías como del recursos facilitan prescripción basada genética; organizaciones promueven realizar determinaciones previo inicio de ciertos Los paneles farmacogenéticos preventivos muestran prometedores, pero requiere investigar biomarcadores poblaciones diversas. El objetivo esta revisión es analizar reciente relación genotipo-respuesta para examinar influye el perfil genético los pacientes tratamientos, áreas investigación que necesitan estudios avanzar hacia una medicina precisión genética. Se realizó búsqueda sistemática identificar artículos investigaran fármacos. estrategia incluyó términos "individualized practice". incluyeron ensayos clínicos, observacionales metaanálisis inglés o español entre 2013–2023. inicial resultó artículos. análisis tras dos investigadores. encontró polimorfismos genéticos respuesta/toxicidad fármacos como: opioides, agonistas GLP-1, tacrólimus, anticoagulantes orales, antineoplasicos, antipsicóticos atípicos, lamotrigina, anti-TNFα, voriconazol, antidepresivos estatinas. Sin embargo, metformina, quetiapina, irinotecán, bisoprolol asociación estadísticamente significativa. analizados sugieren fuerte correlación variabilidad genética fármacos, respaldando importancia usar optimización tratamientos. metformina quetiapina influencia genotipo sigue siendo poco clara. Son necesarios mayor tamaño muestra, diversidad étnica contemplando factores genéticos. falta estandarización métodos accesibilidad desafíos importantes este campo. resumen, muestra un potencial enorme personalizada, aún investigación.

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Differences in Plasma Cannabidiol Concentrations in Women and Men: A Randomized, Placebo-Controlled, Crossover Study

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 10273 - 10273

Published: June 17, 2023

The potential therapeutic benefits of cannabidiol (CBD) require further study. Here, we report a triple-blind (participant, investigator, and outcome assessor) placebo-controlled crossover study in which 62 hypertensive volunteers were randomly assigned to receive the recently developed DehydraTECH2.0 CBD formulation or placebo. This is first have been conducted using over 12-week duration. new formulation's long-term effects on concentrations plasma urine, as well its metabolites 7-hydroxy-CBD 7-carboxy-CBD, analyzed. results concentration ratio for CBD/7-OH-CBD third timepoint (after 5 weeks use) significantly higher than second 2.5 use; p = 0.043). In same timepoints 7-COOH-CBD was observed < 0.001. Differences found between men women. Plasma levels still detectable 50 days after last consumption preparations. Significantly occurred females compared males, potentially related greater adipose tissue. More research needed optimize doses consider differential

Language: Английский

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Long-term efficacy and adverse effects of cannabidiol in adjuvant treatment of drug-resistant epilepsy: a systematic review and meta-analysis

Therapeutic Advances in Neurological Disorders, Journal Year: 2023, Volume and Issue: 16

Published: Jan. 1, 2023

Background: Epilepsy is one of the most common chronic brain diseases. Almost one-third patients have drug-resistant epilepsy (DRE). Cannabidiol being considered as a potential novel drug for treating DRE. Objectives: To investigate long-term efficacy and safety cannabidiol in treatment DRE differences among with different characteristics. Design: Systematic review meta-analysis. Data sources methods: Medline, Embase, CENTRAL were searched literature. RevMan5.4 was used The Intention-to-treat set random effect main analysis. Subgroup analyses performed according to age, dose, concomitant antiseizure medications (ASMs), syndromes, study designs. Results: Fifty studies included this systematic review. A total 4791 participants collected. responder rates (seizure frequency reduced at least 50%) 12-, 24-, 48-, 72-, 96-, 144-week 0.40 [0.36, 0.45], 0.39 [0.34, 0.44], 0.37 [0.30, 0.27 [0.17, 0.37], 0.22 [0.14, 0.30], 0.38 [0.23, 0.53]. Seizure-free 0.04 [0.03, 0.06], 0.05], 0.03 [0.02, 0.03], 0.02 [0.01, 0.06]. Proportion adverse events 0.72 [0.61, 0.83], 0.62 [0.42, 0.81], 0.60 [0.41, 0.79], 0.35 0.56], 0.83 [0.75, 0.90], 0.96 [0.94, 0.99]. pooled proportion serious 0.15 [0.09, 0.21], 0.23 0.31], 0.10 [0.06, 0.15], 0.31 [0.24, 0.38], [0.35, 0.45]. showed that there no significant difference on age subgroups syndromes subgroups. For periods, dose ASMs. However, higher doses more ASMs associated events. Conclusion: has stable fewer early period. Long-term use may decreased increased Dose escalation not increase efficacy, but Furthermore, reduce dosage other without reducing thereby effects. similar effects various syndromes. Trial registration: PROSPERO (CRD42022351250).

Language: Английский

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