Expanding the therapeutic role of highly purified cannabidiol in monogenic epilepsies: A multicenter real-world study

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“Objective: This real-world, retrospective, multicenter study aims to investigate the effectiveness of highly purified cannabidiol (CBD) in a large cohort of patients with epilepsy of genetic etiology due to an identified monogenic cause. Additionally, we examine the potential relationship between specific genetic subgroups and treatment response.

Methods: This study was conducted across 27 epilepsy centers and included patients with monogenic epileptic disorders (pathogenic or likely pathogenic variants) who were treated with highly purified CBD for at least 3 months.

Results: A total of 266 patients (135 females, 50.8%) with monogenic epilepsies were included with a median age at CBD initiation of 12 years (interquartile range [IQR] = 7-19) and a median follow-up duration of 17 months (IQR = 12-24). Overall, 77 different monogenic epilepsies have been included, with the most common genes being SCN1A (32.3%), TSC2 (13.5%), CDKL5, and MECP2 (4.5% each). The mean seizure reduction at the last follow-up was 38.6%, with 47.5% of patients achieving ≥50% seizure reduction and 7.4% achieving seizure freedom. The Clinical Global Impression scale indicated improvement in 65.8% of patients. The general linear mixed model revealed that a shorter maximum duration of seizure freedom before CBD initiation and a higher degree of intellectual disability were independently associated with lower CBD effectiveness. Conversely, no significant differences in seizure outcome were observed across different epilepsy syndromes (Lennox-Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex epilepsy, and other developmental and epileptic encephalopathy), between approved indications and off-label use, or between concomitant clobazam use or not.

Significance: This study supports CBD as a potential treatment for monogenic epilepsies beyond its licensed indications, demonstrating comparable effectiveness between approved and off-label use and suggesting genetic subgroups with promising treatment responses.”

https://pubmed.ncbi.nlm.nih.gov/40126049/

Value of cannabidiol as adjunctive treatment for Lennox Gastaut syndrome: cost-effectiveness and budget impact analysis

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“Background: Lennox-Gastaut syndrome (LGS) is a severe encephalopathic disease that leads to a decrease in the quality of life, physical injury, psychosocial impairment, and a significant increase in treatment costs. Cannabidiol (CBD) is approved for the adjunctive treatment of tonic-colonic seizures in LGS. This study aimed to determine the cost-effectiveness of CBD compared to the usual treatment in patients with LGS syndrome.

Methods: We developed a lifetime-horizon Markov model to compare the cost-effectiveness of adjunctive CBD versus usual care. Additionally, we performed a budget impact analysis over a 5-year time horizon. The findings were presented as the incremental cost-effectiveness ratio (ICER) for CEA, with a willingness to pay threshold of $18,261 per QALY gained, and as the difference in the overall budget ($) between the scenarios with and without CBD for budget impact assessment.

Results: In the base case scenario, CBD was cost-effective compared with usual care $6573 per QALY. Sensitivity analyses substantiated these results. From a healthcare perspective, there is a 77% probability that CBD is cost-effective at a willingness to pay of $18,261 per quality-adjusted life-year (QALY). Overall, the market access of CBD was associated to an increased budget of about $3,459,846 (+ 33%) in the next 5 years simulated.

Conclusions: Compared to usual care, CBD seems to be cost-effective in LGS patients and sustainable, with less than 34% overall budget increased in the next 5 years. Future studies need to confirm our results in the real word setting and in other countries.”

https://pubmed.ncbi.nlm.nih.gov/40038638/

“Our study demonstrates that CBD is valuable as an add-on therapy for patients with LGS in Iran. At current list prices in Iran and assuming a WTP threshold of $18,261/QALY, CBD is cost-effective for the treatment of LGS. So CBD has a more advantage of efficacy compared with usual care and its incremental BI for health system is relatively acceptable. The present study also provides a reference for stakeholders to judge the value of cannabidiol.”

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-025-03972-9

The use of cannabidiol in patients with Lennox-Gastaut syndrome and Dravet syndrome in the UK Early Access Program: A retrospective chart review study

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“Purpose: To evaluate clinical outcomes from the UK Early Access Program in patients aged 2-17 years with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) treated with plant-derived highly purified cannabidiol (CBD; Epidyolex®; 100 mg/mL oral solution).

Methods: Retrospective chart review of data collected from baseline (1 month before CBD treatment initiation) until 12 months’ treatment, CBD discontinuation, death, or loss to follow up.

Results: At baseline, all 26 patients enrolled (LGS, n = 17; DS, n = 9; male, 73 %; mean [range] age, 11.8 [3.0-17.0] years) experienced motor seizures; 92 % were taking ≥ 1 antiseizure medication. Median (IQR) CBD dosage at 6 months (6 M; n = 12) was 6.0 (2.7) mg/kg/day, and 12 months (12 M; n = 9) 7.3 (2.1) mg/kg/day. Median (IQR) percentage change from baseline for motor seizures was – 56.7 % (60.7) at 6 M (n = 20), and – 60.0 % (53.3) at 12 M (n = 15). Patients experiencing ≥ 50 % and ≥ 75 % reduction in motor seizures were 13/20 (65 %) and 5/20 (25 %) at 6 M, respectively, and 10/15 (67 %) and 6/15 (40 %) at 12 M, respectively. Mean (SD) motor seizure-free days/month were 1.5 (4.3) at baseline (n = 24, missing data n = 2), 2.4 (6.3) at 6 M (n = 18), and 2.7 (5.5) at 12 M (n = 15). At 12 M, CBD retention for patients with follow-up data was 14/19 (74 %), whilst 7/26 (27 %) were lost to follow up. The number of patients reporting ≥ 1 adverse event of special interest (most common: gastrointestinal) was 14/20 (70 %) and 8/15 (53 %) at 6 M and 12 M, respectively.

Conclusion: Results demonstrate a reduction in motor seizures and a safety profile consistent with previous studies.”

https://pubmed.ncbi.nlm.nih.gov/39898301/

“Results on CBD effectiveness and safety are consistent with previous studies.”

https://www.sciencedirect.com/science/article/pii/S2589986424000881?via%3Dihub

First case report of effective and safe application of cannabidiol to treat concurrent ALG3-CDG and Lennox-Gastaut Syndrome

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“This study presents the first reported case of a Korean patient with Alpha-1,3-Mannosyltransferase-Congenital Disorder of Glycosylation (ALG3-CDG), characterized by a novel maternally inherited missense mutation and a previously reported paternally inherited nonsense mutation. The patient exhibited typical ALG3-CDG manifestations, including developmental delays, epilepsy, and multisystem involvement, alongside a diagnosis of Lennox-Gastaut Syndrome (LGS).

Cannabidiol therapy, combined with dietary management, led to seizure freedom for over 13 months, significant EEG improvement, and enhanced developmental outcomes.

This case underscores the potential of cannabidiol as a promising treatment strategy for patients with ALG3-CDG and refractory epilepsy, broadening therapeutic perspectives for this rare disorder.”

https://pubmed.ncbi.nlm.nih.gov/39831946/

https://link.springer.com/article/10.1007/s10072-025-08004-1

Update on Cannabidiol in Drug-Resistant Epilepsy

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“Cannabidiol (CBD) has arisen as a promising therapeutic option for children with drug-resistant epilepsy (DRE). CBD has received regulatory nod from different regulatory authorities in the United States, Europe, and India for children with DRE particularly, Dravet syndrome (DS), Lennox Gastaut syndrome (LGS), and Tuberous sclerosis complex (TSC).

Recent clinical trials and observational studies highlight the potential of CBD to lower seizure frequency and provide better quality of life in children affected by these disorders.

The safety profile is generally favorable with minor common adverse events such as somnolence, diarrhea, and gastrointestinal issues. Furthermore, the expense associated with CBD remains a notable concern, especially in low- and middle-income countries such as India, where access to this promising treatment may be constrained. This draws attention to the cost-effective perspective of CBD.

This review aims to explore the pharmacological properties of CBD, its mechanisms of action, and the clinical evidence supporting its use in various pediatric epilepsies, including LGS, DS, and TSC. Additionally, this review sheds light on the current regulatory landscape in India where CBD use is still in its nascent stages, and discusses the challenges and opportunities for integrating CBD into clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/39585547/

https://link.springer.com/article/10.1007/s12098-024-05337-1

Cannabidiol Treatment for Adult Patients with Drug-Resistant Epilepsies: A Real-World Study in a Tertiary Center

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“Background and purpose: Around 30% of patients with epilepsy show drug-resistant epilepsy (DRE). While cannabidiol has demonstrated efficacy as an adjunctive treatment in Dravet syndrome (DS), Lennox-Gastaut Syndrome (LGS), and epilepsy related to tuberous sclerosis complex (TSC), its more global effectiveness in adult patients with DRE apart from these three specific contexts needs to be clarified.

Methods: We conducted a retrospective study at the epilepsy unit of Pitié Salpêtrière Hospital. Patients initiating pharmaceutical cannabidiol treatment and followed for at least 1 year were included. Patients were categorized into “authorized” (LGS, DS, or TSC) and “off-label” groups. Cannabidiol effectiveness and tolerance were compared between groups, and characteristics of responders (patients with >50% reduction in seizure frequency) in the off-label group were examined.

Results: Ninety-one patients, followed by a median duration of 24 months, were included. A total of 35.2% of the patients were in the authorized group. No significant differences were observed in responder rates between groups (31.3% vs. 35.6%, p = 0.85) and retention rates at 1 year (75.0% vs. 74.6%, p = 0.97). Sleepiness was more commonly reported in the authorized group (50.0% vs. 22.0%, p = 0.01), with no other significant differences. Among off-label patients (n = 59), clobazam co-prescription was more prevalent in responders (71.4% vs. 28.9%, p = 0.002).

Conclusion: Our findings suggest that cannabidiol may benefit all adult patients with DRE, particularly those already receiving clobazam. Randomized controlled trials are warranted in off-label patients to validate these observational findings.”

https://pubmed.ncbi.nlm.nih.gov/39501537/

https://onlinelibrary.wiley.com/doi/10.1002/brb3.70122

Cannabinoids and Genetic Epilepsy Models: A Review with Focus on CDKL5 Deficiency Disorder

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“Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers.

The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC).

CBD’s antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids’ pharmacodynamics.

This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid’s potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid’s therapeutic potential for CDD.”

https://pubmed.ncbi.nlm.nih.gov/39409097/

https://www.mdpi.com/1422-0067/25/19/10768

Off-label use of cannabidiol in genetic epileptic and developmental encephalopathies: A case report

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“Developmental Epileptic encephalopathies (DEEs) are severe neurological conditions where cognitive functions appear modulated by both seizure and interictal epileptiform activity.

Cannabidiol (CBD) has been shown to be highly effective in the treatment of drug-resistant seizures in patients with DEEs.

Along with its antiseizure effects, CBD demonstrated clinical beneficial effects in patients’ quality of life, sleep and numerous adaptive behaviors. However, based on the available phase III studies, the indications for this treatment have so far been restricted to Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS) and tuberous sclerosis complex (TSC) by regulatory authorities.

We present the case of a 30-year-old girl with a rare genetic DEE, experiencing relevant seizure frequency reduction together with striking improvement in sleep quality, mood, behavior, language and motor skills after introducing off-label CBD.”

https://pubmed.ncbi.nlm.nih.gov/39040437/

  • “•Cannabidiol exerts also clinical beneficial non-seizure outocomes.
  • •Cannabidiol should be considered in other developmental epileptic encephalopathies.
  • •Cannabidiol presents antiepileptic, neuroprotective and anti-inflammatory effect.”

“Besides its antiseizures effect, CBD might lead to clinical beneficial effects in patients’ quality of life, sleep, cognition and numerous adaptive behaviors. Hopefully, the growing interest in the CBD antiepileptic activity will lead to its use in other developmental and epileptic encephalopathie.”

https://www.sciencedirect.com/science/article/pii/S2589986424000443?via%3Dihub


Effectiveness of Highly Purified Cannabidiol in Refractory and Super-Refractory Status Epilepticus: A Case Series

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“Introduction: Refractory and super-refractory status epilepticus are medical emergencies that must be promptly treated in consideration of their high mortality and morbidity rate. Nevertheless, the available evidence of effective treatment of these conditions is scarce. Among novel antiseizure medications (ASMs), highly purified cannabidiol (hpCBD) has shown noteworthy efficacy in reducing seizures in Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC).

Case presentation: Here, we present two cases of effective use of hpCBD in both refractory and super- refractory status epilepticus. The administration of the nasogastric tube permitted the resolution of status epilepticus without adverse events. At 6-month follow-up, both patients were on hpCBD treatment, which continued to be efficacious for treating seizures.

Conclusion: According to our experience, hpCBD should be taken into consideration as an add-on therapy of RSE and SRSE while also considering the possibility of maintaining this treatment during the follow-up of patients. However, more studies and real-world experiences are needed to better understand its effectiveness in this setting and the interaction with other ASMs.”

https://pubmed.ncbi.nlm.nih.gov/38910424/

https://www.eurekaselect.com/article/141195

CBD in the Treatment of Epilepsy

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“It has been several years since highly purified cannabidiol (CBD) was registered as a medication that can be used in children of at least 2 years of age to treat different types of seizures related to Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and more recently tuberous sclerosis complex (TSC).

During this time, 39 randomized clinical trials (RCTs) and 13 meta-analyses on the efficacy and safety of CBD treatment have been published. Each of the meta-analyses had its own criteria for the RCTs’ inclusion and, therefore, slightly different interpretations of the analyzed data.

Each of them contributed in its own way to the understanding of CBD pharmacology, mechanisms of therapeutic action, development of adverse reactions, and drug-drug interactions. Hence, it seemed reasonable to gather the most relevant data in one article and present all the current knowledge on the use of CBD in epilepsy.

The results of the 13 meta-analyses presented herein confirmed the effectiveness and safety of CBD in children and adolescents with DREs. In adults, reliable conclusions cannot be drawn due to insufficient data.”

https://pubmed.ncbi.nlm.nih.gov/38731471/

https://www.mdpi.com/1420-3049/29/9/1981