Epidiolex (cannabidiol) / Jazz - LARVOL DELTA

A Study to Evaluate the Efficacy and Safety of Cannabidiol Oral Solution (CBD-OS [GWP42003-P, JZP926]) for the Treatment of Focal-Onset Seizures (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Jazz Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Epilepsy

Tuberous Sclerosis Complex (TSC)–Associated Neuropsychiatric Disorders (TAND) Outcomes Following Adjunctive Cannabidiol (CBD) Treatment: 6-Month Intermediate Analysis of the EpiCom Trial (AES 2025) - P4 | "A plant-derived, highly purified pharmaceutical formulation of cannabidiol (CBD; Epidiolex®) is approved for the treatment of seizures associated with TSC; anecdotal evidence also suggests some neuropsychiatric benefits... In this intermediate analysis, reductions were seen in the TAND-SQ and ABC subscale scores and in the severity of behavioral problems reported by caregivers and clinicians after 26 weeks of CBD initiation. The safety profile remains consistent with previous studies. These findings support the continued evaluation of effectiveness of CBD on nonseizure outcomes in patients with TSC."

CNS Disorders • Epilepsy • Infectious Disease • Mental Retardation • Mood Disorders • Psychiatry

Long-Term Use of Cannabidiol (Epidiolex) in Patients with Refractory Epilepsy - The UM Experience (AES 2025) - "The most frequently used prior ASM was clobazam (70%). Purified Pharmaceutical cannabidiol (CBD) provides modest seizure control in refractory epilepsy of multiple types. While adverse events were common, they led to discontinuation in only a quarter of patients. These real-world findings can provide valuable insights into its potential use in other epilepsy types beyond its current FDA-labeled indications."

Clinical • Late-breaking abstract • Anesthesia • CNS Disorders • Epilepsy • Psychiatry

Impact of Cannabidiol (Epidiolex) on Lipid Panel in Patients with Long-Term Use (AES 2025) - "This preliminary analysis suggests that CBD therapy may be associated with dose-dependent alterations in lipid profiles and complex weight changes. These potential effects warrant further investigation to determine their clinical significance. Analysis of the larger, ongoing cohort is necessary to validate these findings."

Clinical • Late-breaking abstract • Cardiovascular • CNS Disorders • Dyslipidemia • Epilepsy

Real-World Polypharmacy and Healthcare Resource Utilization After Early-Line Treatment With Cannabidiol for Lennox-Gastaut Syndrome, Dravet Syndrome, and Tuberous Sclerosis Complex (AES 2025) - "Rationale: In phase 3 clinical trials leading to approval of plant-derived, highly purified cannabidiol (CBD; Epidiolex®, 100 mg/mL oral solution) for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC), trial participants were taking a median of 3 antiseizure medications (ASMs) at baseline and had previously discontinued a median of 4–6 ASMs... In new CBD users with LGS, DS, or TSC, we observed decreases in polypharmacy and HCRU compared with their trends before starting CBD. In the early-line CBD subgroup, further reductions in outcomes, particularly polypharmacy burden and physician office visits, were observed. These results suggest CBD is effective across all lines of therapy, regardless of when initiated."

Clinical • HEOR • Late-breaking abstract • Real-world • Real-world evidence • CNS Disorders • Epilepsy

Cannabidiol Inhibits Phenytoin Clearance and Can Result in Clinical Changes (AES 2025) - "A CBD interaction has been well documented for patients taking clobazam (CLB) but not for PHT...On presentation, he was taking levetiracetam, clonazepam, and PHT (which mom reported minimized the frequency and severity of his tonic-clonic seizures)...Epidiolex (CBD) was initiated according to the standard titration... These two cases show CBD inhibition of PHT metabolism can lead to significant increases in levels and meaningful clinical changes (in one case sz control and in the other drug toxicity). In case 1, clinical benefit may also relate to the increase in CLB metabolite and direct effect of CBD. However, the recurrence of seizures on lowering the PHT dose and the resumption of improved control once PHT was restored suggests the elevated PHT was most significant."

Clinical • Late-breaking abstract • Ataxia • CNS Disorders • Epilepsy • Movement Disorders • Ophthalmology • CYP2C19

Real-World Effectiveness of Cannabidiol on Antiseizure Medication Cycling, Polypharmacy, and Healthcare Resource Utilization: A US Claims Analysis (AES 2025) - "Rationale: Efficacy of cannabidiol (CBD; Epidiolex®, 100 mg/mL oral solution) for treatment of seizures associated with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and tuberous sclerosis complex (TSC) has been established by randomized clinical trials... These real-world insights indicate overall reductions in ASM cycling, polypharmacy burden, and HCRU at 12 months post–CBD initiation in both pediatric and adult patients with DS, LGS, or TSC. An overall reduction in these parameters suggests that CBD may help reduce the clinical and economic burden of disease in both pediatric and adult patients living with these rare epilepsies."

Clinical • HEOR • Real-world • Real-world effectiveness • Real-world evidence • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation

A temporary spike: investigating Lennox-Gastaut syndrome incidence in the US following FDA approval of cannabidiol (CBD) (AES 2025) - "Funding: None Rationale: In June 2018, the US Food and Drug Administration (FDA) approved pharmaceutical grade cannabidiol (CBD; Epidiolex®) for the treatment of seizures associated with Lennox Gastaut syndrome (LGS)... This work sheds light on the clinical and research importance of appropriately using the LGS ICD code and ensuring accurate, reliable diagnosis of LGS based upon standardized, well-defined criteria."

CNS Disorders • Epilepsy

Phase 1, Open-Label, Fixed-Sequence, Bidirectional, Pharmacokinetic Drug-Drug Interaction Study Between Cannabidiol and Cenobamate in Healthy Adult Participants (AES 2025) - "Rationale: A plant-derived highly purified pharmaceutical formulation of cannabidiol (CBD; Epidiolex®; 100 mg/mL oral solution) is approved for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. No PK effect of CBD on CNB or of CNB on CBD was observed when the two were administered concomitantly at clinically relevant dosages. Coadministration of CBD and CNB showed no evidence of increased AEs or worsening safety findings compared with either dosed alone. These PK DDI results support that coadministration of CNB with CBD does not warrant a reduction in the CBD dosage."

Clinical • Late-breaking abstract • P1 data • PK/PD data • CNS Disorders • Dermatitis • Dermatology • Epilepsy • Immunology

Effectiveness of Cannabidiol in Patients With Rare Epilepsies Compared to External Placebo Control: A Post Hoc Analysis From the Expanded Access Program (AES 2025) - "CBD effectiveness was compared with an external placebo control arm (ECA) from LGS RCTs. Patients received plant-derived, highly purified CBD (Epidiolex®, 100 mg/mL oral solution), increasing from 2 to 10 mg/kg/day as tolerated or a maximum of 25–50 mg/kg/day, based on EAP site...At baseline, mean age ranged from 5.0 to 14.4 years and most commonly used antiseizure medications (ASMs) were clobazam (40%) and levetiracetam (33%)... CBD treatment was associated with reductions in convulsive and total seizure frequency in patients with DEEs and rare epilepsies in a cohort that excluded patients with LGS, DS, and TSC. These findings suggest that CBD may be an effective ASM for a broad range of DEEs and other rare epilepsies and warrants further investigation."

Clinical • Retrospective data • Absence Seizure Disorder • CNS Disorders • Epilepsy • Infectious Disease • CDKL5

An Observational Analysis of Social Media Content Pertaining to Use of Cannabidiol for Epilepsy (AES 2025) - "Search terms included epilepsy, cannabidiol, CBD, Epidiolex, Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis... The availability of cannabidiol as a drug for a small group of refractory epilepsies offers an attractive therapeutic option in these difficult cases. However, given the nature of the substance, it is prone to misinformation. Specifically, the implication that recreational marijuana may be used in the treatment of epilepsy is a dangerous presence on social media, with far-reaching consequences for epilepsy patients."

CNS Disorders • Epilepsy

An Assessment of Acute Pharmacodynamic Drug-Drug Interactions Between Cannabidiol and Cenobamate in a Mouse Model of Generalized Tonic Seizures (AES 2025) - "Previously, we identified a synergistic antiseizure pharmacodynamic drug-drug interaction (PD-DDI) between cannabidiol (CBD) and clobazam using the maximal electroshock seizure (MES) model in mice.1 Cenobamate (CNB) has been shown to enhance the antiseizure activity of other ASMs using the DBA/2 mouse model.2 The current study investigates PD-DDIs for CBD and CNB in the mouse MES model. The MES model1 of acute generalized seizures was used in male C57BL/6J mice to evaluate antiseizure properties of CBD alone, CNB alone, and in combination. Mice were treated with either CNB (1–30 mg/kg intraperitoneally [IP]; 30 min) or plant-derived highly-purified CBD (Epidiolex® active pharmaceutical ingredient, 10–100 mg/kg IP; 60 min), before receiving a validated, fixed-current-intensity electrical stimulus via corneal stimulation (30 mA, 0.2 sec)... This study demonstrates a novel synergistic PD-DDI between CBD and CNB in the mouse MES model of acute generalized seizures and..."

Late-breaking abstract • PK/PD data • Preclinical • CNS Disorders • Epilepsy

Fintepla and Epidiolex: An Overview of Concomitant Use (AES 2025) - "Approximately 63% of patients in our population reported improved seizure frequency or reduced intensity of seizures on the combination of CBD and FFA. Only 20% of patients who remained on the combination reported side effects, while 100% who stopped either CBD or FFA described side effects during follow up visits. When reviewing efficacy and adverse effects, there were confounding factors including the addition of or dose changes of other anti seizure medications and the pursuit of surgical intervention (CC) or neuromodulation (namely DBS)."

CNS Disorders • Epilepsy

Cenobamate in Generalized Epilepsies: Case Reports in Juvenile Myoclonic Epilepsy and PCDH19-Related Epilepsy (AES 2025) - "We present two cases demonstrating significant clinical response to off-label cenobamate use in generalized epilepsy syndromes. Retrospective case series of two females with drug-resistant generalized epilepsy syndromes treated with off-label cenobamate. Case 1 (JME): A 22-year-old female with JME experienced absence, myoclonic, and generalized tonic-clonic seizures (GTCs) refractory to multiple ASMs, including valproate, lamotrigine, topiramate, and zonisamide...Trials of oxcarbazepine, zonisamide, and lacosamide failed; VNS and cannabidiol (Epidiolex) offered partial benefit... These cases highlight the promising role of cenobamate as an off-label adjunctive treatment in refractory generalized epilepsies. In both patients, cenobamate significantly reduced seizure frequency and allowed withdrawal or dose reduction of prior ASMs with unfavorable side-effect profiles. Given its favorable pharmacodynamic profile and real-world efficacy, further clinical trials are..."

Case report • Clinical • Absence Seizure Disorder • Alopecia • CNS Disorders • Epilepsy • Movement Disorders

A Population Health Study of Patients Prescribed Cannabidiol in the Epilepsy Learning Healthcare System (ELHS) Registry (AES 2025) - "In collaboration with Jazz Pharmaceuticals, ELHS conducted a retrospective analysis on a de-identified subset of patients with documented use of FDA-approved cannabidiol (CBD; Epidiolex®, 100 mg/mL oral solution) to evaluate real-world data-capture patterns and identify opportunities to enhance learning and optimization of health system infrastructure... This analysis with documented CBD use for ≥ 6 months highlights the potential of ELHS to inform real-world treatment patterns. With support for improved and consistent adoption, the structured CRFs used in ELHS can provide opportunities to perform studies on treatment outcomes at individual and population levels across clinical centers, as well as close gaps left by data collected for clinical trials and administrative claims analyses."

Clinical • Late-breaking abstract • CNS Disorders • Epilepsy

Development of Novel Cannabinoid Derived Therapeutics for the Treatment of Refractory Epilepsy (AES 2025) - "These novel CBD analogs represent a promising solution to the limitations of CBD. By offering improved efficacy, safety, and pharmacokinetics, these new drug candidates have the potential to benefit patients with refractory epilepsies who do not respond to Epidiolex®, as well as those with other challenging epileptic disorders such as developmental epileptic encephalopathy (DEE)."

CNS Disorders • Epilepsy • GPR55 • TRPV1

Cannabidiol Efficacy in Patients With Lennox-Gastaut Syndrome With Developmental and Epileptic Encephalopathy-Associated Genetic Variants: A Subgroup Analysis (AES 2025) - P3 | "Cannabidiol (CBD; Epidiolex®, 100 mg/mL oral solution) is FDA approved for the treatment of seizures associated with LGS, Dravet syndrome, and tuberous sclerosis complex in patients ≥ 1 year of age... In participants with LGS secondary to a genetic DEE, CBD efficacy and safety appears consistent with that observed in the overall LGS pivotal trial populations."

Clinical • CNS Disorders • Epilepsy

Industry Supported Scientific Exhibit | Epidiolex® (cannabidiol): Shaping the Future of Epilepsy Treatment Through Research and Innovation (AES 2025) - "Sponsored by Jazz Pharmaceuticals, Inc."

CNS Disorders • Epilepsy

A Phase 1b, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Cannabidiol Oral Solution (CBD-OS [GWP42003-P, JZP926]) for the Treatment of Focal-Onset Seizures (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: Jazz Pharmaceuticals

New P1 trial • CNS Disorders • Epilepsy

Cannabidiol exerts anti-inflammatory effects but maintains T effector memory cell differentiation in humans. (PubMed, JCI Insight) - "Cannabidiol exhibits mixed immunomodulatory effects with pro- and anti-inflammatory signals. Understanding the clinical safety of cannabidiol use is important given the paucity of pain control options available for immunocompromised transplant populations."

Journal • Pain • Transplantation • IL10 • IL2 • IL6 • TNFA

Uncovering the mechanism by which Cannabidiol (CBD) decreases seizure burden in a mouse model of viral induced epilepsy (Neuroscience 2025) - "Cannabidiol (CBD), approved by the FDA and commercialized as Epidiolex, effectively reduces seizure frequency for patients with certain genetic epilepsies...Furthermore, we plan to investigate oral administration of CBD, which is more aligned with clinical applications. This research advances our understanding of cannabinoid-based therapies; future studies are needed to further investigate the anti-inflammatory properties of CBD and other cannabinoids."

Preclinical • CNS Disorders • Epilepsy • IL6 • TNFA

Mechanistic study of the cytotoxicity of cannabidiol and its metabolites in HepG2 cells. (PubMed, Arch Toxicol) - "The cannabidiol (CBD)-based drug, Epidiolex, received approval from the U.S. Food and Drug Administration (FDA) for treating seizures in certain childhood-onset epileptic disorders...In summary, autophagy emerges as the common mechanism underlying CBD-, 7-hydroxy-CBD-, and 7-carboxy-CBD-induced cytotoxicity. Inhibition of mitochondrial respiratory complexes and mitochondrial dysfunction were observed with CBD and 7-hydroxy-CBD, but not with 7-carboxy-CBD."

Journal • CNS Disorders • Epilepsy • Metabolic Disorders

Anti-convulsant efficacy of long-acting injectable cannabidiol formulation (IVL5005) in the pentylenetetrazol-induced convulsions, with pharmacokinetic characterization. (PubMed, Front Pharmacol) - "Epidiolex®, an FDA-approved oral CBD solution, is indicated for rare epileptic disorders such as Lennox-Gastaut syndrome and Dravet syndrome...The optimized formulation was selected for efficacy evaluation in a pentylenetetrazole (PTZ)-induced convulsion model...No hepatic toxicity was observed with IVL5005, while liver changes were detected in the oral CBD group, likely due to extensive first-pass metabolism. These results indicate that IVL5005 may overcome key limitations of oral CBD and support its further development as a long-acting therapeutic option for epilepsy."

Journal • PK/PD data • CNS Disorders • Epilepsy

Cannabidiol metabolites identified by LC-QTOF after controlled dosing. (PubMed, J Anal Toxicol) - "CBD concentrations were higher when CBD was administered as Epidiolex compared to synthetically derived CBD in oral syrup or vaping. In conclusion, the results support the use of 7-hydroxy-CBD as a marker of CBD exposure in hydrolyzed urine, but also identified several novel metabolites that might further our understanding of CBD pharmacokinetics."

Journal • CNS Disorders • Epilepsy

Cannabidiol as Adjunctive Treatment in Drug-Resistant Epilepsy With Epileptic Spasms Beyond Two Years of Age. (PubMed, Pediatr Neurol) - "CBD appears to be an effective and well-tolerated adjunctive treatment for drug-resistant ES in children older than 2 years. Significant response rates were found, particularly in patients with Down syndrome and malformations of cortical development. Future studies with larger cohorts and longer follow-up are needed to validate these findings and explore the potential for earlier use of CBD in treatment-resistant epilepsy."

Journal • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation