“Objective: Cannabidiol (CBD) is one of the most prominent non-psychotropic cannabinoids with known therapeutic potentials. Based on its anti-seizure efficacy, the first cannabis derived pharmaceutical grade CBD-based medication was approved in the USA in 2018 for the treatment of seizures in patients 2 years and older. Despite the effectiveness in reducing seizures, there remain several major questions on the optimization of CBD therapy for epilepsy such as the optimal dosage, composition, and route of delivery, which are the main objective of this current study.

Methods: We evaluated the antiseizure effects of CBD through different compositions, routes of delivery, and dosages in a pre-clinical model. We used a kainic acid-induced epilepsy model in C57BL/6 mice, treated them with placebo and/or CBD through inhalation, oral, and injection (intraperitoneal) routes. We used CBD broad spectrum (inhaled and intraperitoneal) vs CBD isolate formulations. We employed the Racine scaling system to evaluate the severity of the seizures, flow cytometry for measuring immune biomarkers and neurotrophic factors, and histologic analysis to examine and compare the groups.

Results: Our findings showed that all forms of CBD reduced seizures severity. Among the combination of CBD tested, CBD broad spectrum via inhalation was the most effective in the treatment of epileptic seizures (p < 0.05) compared to other forms of CBD treatments.

Conclusion: Our data suggest that route and CBD formulations affect its efficacy in the prevention of epileptic seizures. Inhaled broad spectrum CBD showed a potential superior effect compared to other delivery routes and CBD formulations in the prevention of epileptic seizures, which warrants further research.”

https://pubmed.ncbi.nlm.nih.gov/40177581/

https://www.degruyterbrill.com/document/doi/10.1515/tnsci-2022-0362/html

“Pharmaceutical-grade cannabidiol (CBD) is an alternative treatment for patients with drug-resistant epilepsy (DRE). In 2022, the Italian Hospital of Buenos Aires implemented a non-medical change (NMC) of treatment, replacing one commercial pharmaceutical-grade CBD product with another, the latter also being the initial option for new patients.

Our objective was to evaluate the clinical outcomes of the commercial product change in this population.

Methods: Retrospective cohort of DRE patients who either switched from one commercial pharmaceutical-grade CBD product to another or started treatment with the new product. The clinical response was evaluated by changes in seizure frequency, perception of change with the Patient Global Impression of Change (PGIC) scale, and safety considering discontinuation and/or the presence of adverse effects.

Results: Nineteen patients were included, 12 in the change group and 7 in the new start group (7 pediatric and 12 adults). One patient discontinued treatment due to lack of response. Among those who completed follow-up, 8 (44%) reduced seizure frequency, 6 (33%) showed no change, and 4 (22%) increased seizure frequency. According to the PGIC scale, 9 (50%) remained unchanged, 5 (28%) reported barely noticeable changes, and 4 (22%) reported improvement. Adverse events were mild and transient.

Conclusion: The new commercial pharmaceutical-grade CBD product is a safe and valid option both for substitution and initial treatment in patients with DRE. During the treatment period, patients perceived stability or improvement according to the PGIC scale.”

https://pubmed.ncbi.nlm.nih.gov/40163830/

“Epilepsy is the fourth most common neuropsychiatric disorder. Although the approval of Epidiolex has ignited hope for patients, there is still a large gap in the field of anti-seizure research. The effect and underlying mechanism of full-spectrum hemp extract (HE) remains unclear.

Here this study investigated the anti-seizure effect of HE on seizure models. The results showed that HE significantly reduced seizure susceptibility and prolonged seizure latency with better pharmacokinetic performance compared to CBD.

This article then further explored the anti-seizure active components and their possible mechanism in HE. The results indicated that cannabichromene (CBC) and cannabinol (CBN) were involved in the anti-seizure process, especially CBC showed a strong allosteric enhancement effects on CBD binding site of the GABAA receptor, which implied that the GABAA receptor seemed to be the primary anti-epileptic target of HE.

This article not only presents the great potential of HE as a candidate for new anti-epileptic drugs with less psychoactive, but also provides a valuable contribution to subsequent mechanism research and drug development on epilepsy.”

https://pubmed.ncbi.nlm.nih.gov/40166106/

https://www.sciencedirect.com/science/article/pii/S2667325824004552?via%3Dihub

“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/

“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