Cannabis Epilepsy Research

Cannabidiol Lacks Direct Effect on Cortical Excitability: A Randomized, Double Blind, Placebo Controlled, 3-Way Crossover Trial.

Gorbenko, Andriy A · 2026

Single doses of 30 mg and 700 mg CBD had no significant effects on single-pulse or paired-pulse TMS-EMG measures of cortical excitability, nor on validated CNS sedation tests, compared to placebo — suggesting CBD may lack intrinsic anti-epileptic and sedative properties..

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

Cerulli Irelli, Emanuele · 2025

47.5% of patients achieved 50% or greater seizure reduction; 7.4% became seizure-free; no significant difference between approved indications and off-label use; shorter prior seizure-free periods and greater intellectual disability predicted lower effectiveness..

Assessing Real World Efficacy, Safety, and 18-Month Retention Rates of Cannabidiol in Individuals With Drug Resistant Epilepsies.

Chemaly, Nicole · 2025

54% of caregivers reported reduced seizure frequency at 1 month; 48% maintained improvement at 2-6 months; communication (60%), alertness (54%), and motor skills (44%) also improved; 55% retention at 18 months; off-label use had higher retention than approved indications..

Dysregulation of the Cannabinoid System in Childhood Epilepsy: From Mechanisms to Therapy.

Montebello, Gloria · 2025

The endocannabinoid system regulates neuronal excitability from early life through aging.

A multicenter study on the use of purified cannabidiol for children with treatment-resistant developmental and epileptic encephalopathies.

Reyes Valenzuela, Gabriela · 2025

In 551 children with drug-resistant developmental and epileptic encephalopathies treated with purified CBD at 10 centers, 50.6% achieved at least 50% seizure reduction after 12-32 months, including 14.2% who became seizure-free.

Efficacy and safety of cannabidiol in children with developmental and epileptic encephalopathies: A systematic review.

Saranti, Anna · 2025

Pharmaceutical CBD (up to 50 mg/kg/day) achieved 50% or greater seizure reduction in at least 20% of participants in 11 of 14 included studies.

Update on Cannabidiol in Drug-Resistant Epilepsy.

Singh, Akanksha · 2025

CBD has been approved for Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex in multiple countries.

Clinically Meaningful Reduction in Drop Seizures in Patients with Lennox-Gastaut Syndrome Treated with Cannabidiol: Post Hoc Analysis of Phase 3 Clinical Trials.

Specchio, Nicola · 2025

Using CGIC of 'slightly improved' or better, the threshold for clinically meaningful drop seizure reduction was 30.6%, with 57.7% of patients meeting this threshold.

Retrospective Multicenter Chart Review Study of Adjunctive Cannabidiol for Seizures Associated with Lennox-Gastaut Syndrome, Dravet Syndrome and Tuberous Sclerosis Complex.

Strzelczyk, Adam · 2025

Responder rates (>=50% seizure reduction) for total seizures: 43.3% at 3 months, 44.0% at 12 months.

Real-world experience of cannabidiol in conjunction with clobazam for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome: Results from a retrospective multicentre chart review in Germany.

Strzelczyk, Adam · 2025

50%+ seizure reduction in total seizures: 47.5% at 3 months, 45.5% at 12 months.

Availability and affordability of cannabinoids for epilepsy treatment across different geographic settings-A survey from the ILAE Plant-Based Therapy Task Force.

Vinayan, Kollencheri Puthenveettil · 2025

Of 86 responding ILAE chapters (68% response rate), only 32 countries had regulatory approval for cannabinoids in epilepsy, with 21 approving only CBD.

Cost-Utility Analysis of Add-on Cannabidiol vs Usual Care Alone for the Treatment of Seizures in Patients With Treatment-Resistant Lennox-Gastaut Syndrome or Dravet Syndrome in the Netherlands.

Siddiqui, Jamshaed · 2024

For Lennox-Gastaut syndrome (LGS), adding CBD cost an extra 28,338 euros but gained 1.318 QALYs, yielding a cost per QALY of 21,493 euros, well below the Dutch willingness-to-pay threshold of 80,000 euros.

Therapeutic and clinical foundations of cannabidiol therapy for difficult-to-treat seizures in children and adults with refractory epilepsies.

Reddy, Doodipala Samba · 2023

Randomized clinical trials support CBD for seizures in three rare epileptic encephalopathies: Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex.

Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity.

Rosenberg, Evan C · 2023

LPI increased excitatory presynaptic release probability and evoked synaptic strength in hippocampal CA3-CA1 connections while simultaneously weakening inhibitory signaling by decreasing GABA receptor (GABAARgamma2) and gephyrin puncta.

Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications.

Bilbao, Ainhoa · 2022

CBD showed high-grade evidence for epilepsy (SMD -0.5) and moderate-grade for Parkinsonism (SMD -0.41).

Use of cannabidiol in the treatment of epilepsy.

Mazurkiewicz-Bełdzińska, Maria · 2022

CBD was isolated from cannabis in 1940 and has a confirmed anti-seizure effect without psychoactive activity.

Cannabidiol for the treatment of refractory epilepsy in children: a critical review of the literature.

Moreira, Gabriela Araujo · 2022

CBD efficacy for treating seizures has been confirmed by RCTs for LGS, Dravet syndrome, and TSC.

Use of cannabidiol in the treatment of epilepsy: Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex.

Silvinato, Antônio · 2022

CBD compared to placebo reduced seizure frequency by 33%, increased 50% seizure reduction by 20%, increased seizure freedom by 3%, and improved caregiver-assessed clinical impression by 21% in patients with refractory epilepsy..

Cannabidiol in the treatment of epilepsy: Current evidence and perspectives for further research.

Franco, Valentina · 2021

Pharmaceutical-grade CBD has been approved for seizures in Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex based on multiple randomized placebo-controlled trials.

Cannabidiol in conjunction with clobazam: analysis of four randomized controlled trials.

Gunning, Boudewijn · 2021

CBD reduced primary seizure frequency versus placebo in LGS (treatment ratio 0.70) and Dravet syndrome (0.71) in the overall population.

Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial.

Thiele, Elizabeth A · 2021

Both CBD doses significantly reduced TSC-associated seizures versus placebo: 48.6% reduction for 25 mg/kg/day (30.1% reduction from placebo, p<0.001) and 47.5% for 50 mg/kg/day (28.5% from placebo, p=0.002), with no additional benefit from the higher dose but more adverse effects..

Emerging Use of Epidiolex (Cannabidiol) in Epilepsy.

Abu-Sawwa, Renad · 2020

Epidiolex was FDA-approved June 2018 for patients aged 2+ with Dravet or Lennox-Gastaut syndrome.

Adverse effects of cannabinoids.

Anciones, Carla · 2020

Short-term CBD side effects are generally transitory, dose-dependent, and mild to moderate: somnolence, decreased appetite, and diarrhea.

Does cannabidiol have antiseizure activity independent of its interactions with clobazam? An appraisal of the evidence from randomized controlled trials.

Bialer, Meir · 2020

47-68% of CBD trial patients were taking clobazam, which shows complex interactions with CBD (3.4-5 fold norclobazam increase).

Cannabinoids and the expanded endocannabinoid system in neurological disorders.

Cristino, Luigia · 2020

Beyond the classical CB1/CB2 system, an expanded "endocannabinoidome" includes biochemically related mediators with their own receptors and enzymes.

Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials.

Devinsky, Orrin · 2020

CBD vs.

Cannabis-based products for pediatric epilepsy: An updated systematic review.

Elliott, Jesse · 2020

Data from both RCTs and non-randomized studies suggest cannabidiol reduces seizure frequency as adjunctive treatment, though RCTs showed no statistically significant difference for seizure freedom, quality of life, or sleep disruption compared to placebo..

Adjunctive Cannabidiol in Patients with Dravet Syndrome: A Systematic Review and Meta-Analysis of Efficacy and Safety.

Lattanzi, Simona · 2020

Pooling three RCTs with 359 participants (228 CBD, 131 placebo), adjunctive CBD was associated with a 69% higher likelihood of achieving 50% or greater reduction in convulsive seizures (RR 1.69, 95% CI 1.21-2.36, p=0.002).

Cannabidiol efficacy and clobazam status: A systematic review and meta-analysis.

Lattanzi, Simona · 2020

Across four RCTs with 714 participants, CBD was associated with significantly higher seizure response rates compared to placebo both in patients taking clobazam (52.9% vs 27.8%, RR=1.85) and those not taking it (29.1% vs 15.7%, RR=1.80).

Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects.

Morano, Alessandra · 2020

Pharmaceutical CBD (Epidiolex) was approved based on four pivotal RCTs enrolling 154 Dravet and 396 Lennox-Gastaut syndrome patients.

Efficacy of cannabinoids in paediatric epilepsy.

Ali, Shayma · 2019

CBD produced a 38-41% median reduction in all seizures compared to 13-19% on placebo in three RCTs for Dravet and Lennox-Gastaut syndromes.

Cannabinoid therapy in epilepsy.

Billakota, Santoshi · 2019

Epidiolex (>99% CBD, <0.10% THC) received FDA approval for Dravet and Lennox-Gastaut syndromes and EMA approval for Lennox-Gastaut syndrome, based on Phase III RCTs and open-label trials demonstrating efficacy and safety.

Cannabidiol: A New Hope for Patients With Dravet or Lennox-Gastaut Syndromes.

Chen, Jeffrey W · 2019

In the GWPCARE trial series, CBD reduced key seizure frequencies by 17-23% compared to placebo as adjunctive therapy in patients 2+ years old.

Cannabis-based products for pediatric epilepsy: A systematic review.

Elliott, Jesse · 2019

CBD reduced median monthly seizure frequency by 19.8% vs placebo (95% CI: -27.0% to -12.6%) and increased the proportion achieving 50%+ seizure reduction (RR = 1.76).

Pharmacological and Therapeutic Properties of Cannabidiol for Epilepsy.

Franco, Valentina · 2019

CBD at 10 and 20 mg/kg/day was superior to placebo in reducing drop seizures (LGS) and convulsive seizures (DS) across four RCTs.

Safety, efficacy, and mechanisms of action of cannabinoids in neurological disorders.

Friedman, Daniel · 2019

Randomized controlled trials provide evidence of CBD's anti-seizure effects for Lennox-Gastaut and Dravet syndromes.

Cannabidiol as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome.

Lattanzi, S · 2019

The review critically examined CBD's pharmacology and recent clinical trial data showing its efficacy and safety as add-on treatment for LGS and DS, two severe childhood epilepsy syndromes where existing treatments fail to control seizures in most cases..

Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results.

Laux, Linda C · 2019

At 12 weeks, CBD reduced median monthly major motor seizures by 50% and total seizures by 44%.

A systematic review of cannabidiol dosing in clinical populations.

Millar, S A · 2019

23 of 35 studies reported significant improvement in primary outcomes.

A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects.

Morrison, Gilmour · 2019

CBD increased N-desmethylclobazam (active clobazam metabolite) 3.4-fold for both Cmax and AUC.

Progress report on new antiepileptic drugs: A summary of the Fourteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIV). II. Drugs in more advanced clinical development.

Bialer, Meir · 2018

This progress report from the Fourteenth Eilat Conference on New Antiepileptic Drugs documented a landmark regulatory event: on June 25, 2018, the FDA approved a standardized cannabidiol oral solution (Epidiolex) for treating seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients 2 years and older. The report placed cannabidiol within the broader context of antiepileptic drug development, alongside other compounds in advanced clinical development including cannabidivarin, fenfluramine, ganaxolone, and several others.

Medical Use of Cannabinoids.

Fraguas-Sánchez, Ana Isabel · 2018

This extensive review covered the therapeutic landscape of cannabinoids across dozens of medical conditions. Six cannabinoid medications had already received regulatory approval: nabilone and dronabinol capsules for chemotherapy nausea and vomiting, dronabinol capsules and oral solution for anorexia, THC:CBD oromucosal spray (Sativex) for MS-related spasticity and cancer pain, and CBD oral solution (Epidiolex) for Dravet and Lennox-Gastaut epilepsy syndromes. Beyond approved uses, the review found evidence supporting potential applications in inflammatory and neuropathic pain, various cancer types (brain, breast, prostate), neurodegenerative diseases (Parkinson's, Huntington's, Alzheimer's), PTSD and anxiety disorders, irritable bowel syndrome, eye diseases, and substance abuse disorders (particularly alcohol and opioid). The endocannabinoid system's involvement in energy balance, appetite, blood pressure, pain modulation, nausea, memory, learning, and immune response explains the breadth of potential therapeutic applications..

Cannabis for the Treatment of Epilepsy: an Update.

Gaston, Tyler E · 2018

This review compiled all available evidence on cannabis-derived treatments for epilepsy, from artisanal products through FDA-approved purified CBD. While artisanal CBD products showed high rates of reported seizure improvement in surveys and retrospective studies, these lacked controlled dosing and rigorous design. The stronger evidence came from open-label expanded access programs (EAPs) and randomized controlled trials of highly purified CBD (Epidiolex).

Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis.

Lattanzi, Simona · 2018

Researchers pooled data from four randomized, placebo-controlled trials of oral CBD as add-on therapy in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) whose seizures were not controlled by existing medications. Both CBD dose levels showed similar efficacy: the pooled difference in seizure frequency reduction was 19.5 percentage points (95% CI 8.1-31.0) for 10 mg/kg/day and 19.9 percentage points (95% CI 11.8-28.1) for 20 mg/kg/day compared to placebo. The higher dose carried more risk: treatment withdrawal risk was 4.20 times higher for 20 mg/kg/day (95% CI 1.82-9.68) versus placebo but not significantly elevated for 10 mg/kg/day (RR 1.45, 95% CI 0.28-7.41). Adverse events occurred in 87.9% of CBD patients versus 72.2% on placebo (RR 1.22).

Cannabidiol for Epilepsy: New Hope on the Horizon?

Sanmartin, Paul E · 2018

Early anecdotal evidence for cannabis as an anticonvulsant was recently replaced by high-quality data from randomized controlled studies.

Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence.

Stockings, Emily · 2018

CBD 20 mg/kg/day achieved 50%+ seizure reduction more than placebo (RR 1.74, NNT=8).

Cannabinoids in treatment-resistant epilepsy: A review.

O'Connell, Brooke K · 2017

This review traced the evolution of cannabis-based epilepsy treatment from millennia of traditional use to modern randomized controlled trials. The strongest evidence centered on Epidiolex (purified CBD at 100 mg/mL).

Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?

Perucca, Emilio · 2017

After years of uncontrolled observations and anecdotal reports, three rigorous placebo-controlled trials of purified CBD (Epidiolex) provided the first class 1 evidence that CBD improves seizure control in specific epilepsy syndromes. In Dravet syndrome, CBD reduced the frequency of convulsive seizures (tonic-clonic, tonic, clonic, and atonic) compared to placebo.

Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.

Rosenberg, Evan C · 2017

The review surveyed decades of preclinical research on plant cannabinoids in models of seizures, epilepsy, epileptogenesis (the development of epilepsy), and seizure-related neuroprotection. In simple acute seizure models, activating CB1 receptors typically reduced seizures, and blocking them worsened seizures.

Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

Devinsky, Orrin · 2017

Cannabidiol (20 mg/kg/day) reduced convulsive seizure frequency by 39% compared to 13% with placebo in children with Dravet syndrome.

Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders [RETIRED]: report of the Guideline Development Subcommittee of the American Academy of Neurology.

Koppel, Barbara S · 2014

This systematic review by the American Academy of Neurology evaluated 34 studies (8 Class I) on medical marijuana for neurological conditions.

A systematic review of highly purified cannabidiol in developmental and epileptic encephalopathies and complex treatment-resistant epilepsies: Changes in seizure frequency and adverse events.

Coppola, Antonietta · 2026

CBD reduced seizure frequency in at least one patient across 47 of 57 studies, spanning 37 different developmental and epileptic encephalopathies (DEEs) and treatment-resistant epilepsies (TREs).

Cannabidiol as Adjunctive Treatment in Drug-Resistant Epilepsy With Epileptic Spasms Beyond Two Years of Age.

González-Alguacil, Elena · 2026

Of 53 patients with drug-resistant childhood epileptic spasms treated with purified CBD (Epidyolex), 58.5% achieved ≥50% reduction in spasm frequency and 15% became completely spasm-free, with the highest response rates in patients with cortical malformations and Down syndrome..

A temporary spike: Investigating Lennox-Gastaut syndrome incidence in the US following FDA approval of cannabidiol.

Marcinski Nascimento, Kaley J · 2026

Annual LGS incidence rose ~30% from 2018 to 2019 and ~60% from 2017 to 2019, before returning to pre-approval baseline (2020-2023).

Unveiling Neurological Benefits: A Review of Hemp Leaf, Flower, Seed Oil Extract, and Their Phytochemical Properties in Neurological Disorders.

Purushothaman, Atchuthan · 2026

This review synthesized evidence on how different parts of the hemp plant — seeds, leaves, and flowers — contain distinct bioactive compound profiles with relevance to neurological disorders. Flowers are richest in cannabinoids (particularly CBD) and terpenes, which interact with the endocannabinoid system, neurotransmitter receptors, and inflammatory pathways.

Adjunctive cannabidiol in intractable pediatric epilepsy: A retrospective study on tolerability, efficacy, and safety across genetic and nongenetic etiologies.

Shim, Youngkyu · 2026

At 12 months, 79.3% of patients achieved 50% or greater seizure reduction and 34.5% achieved 75% or greater reduction without generalized motor seizures.

Long-term plasma monitoring of THC and CBD in pediatric drug-resistant epilepsy: Implications for cannabidiol therapy with Epidyolex®.

Cafaro, Alessia · 2025

THC was undetectable (<0.2 mcg/L) at all timepoints across all 38 patients throughout the study period (2019-2024).

Prevalence of cannabis use disorders and associated factors among privately insured adults with epilepsy.

Czerniak, Katarzyna · 2025

CUD prevalence was 1.1%.

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

Eltze, Christin · 2025

At 12 months, median motor seizure reduction was 60%, with 67% of patients achieving at least 50% reduction and 40% achieving at least 75% reduction.

Cannabidiol in Drug-Resistant Epilepsy (DRE) in Children: A Retrospective Study.

Gowda, Vykuntaraju K · 2025

In a retrospective review of 50 children with drug-resistant epilepsy (mostly Lennox-Gastaut syndrome), CBD as add-on therapy produced complete seizure response (>90% reduction) in 10 children, partial response (30-90% reduction) in 18, and no response in 14.

Use of cannabidiol for off-label treatment of patients with refractory focal, genetic generalised and other epilepsies.

Hollander, Marie · 2025

Add-on CBD showed meaningful seizure reduction across epilepsy types beyond its approved indications (Lennox-Gastaut, Dravet, TSC).

Cannabinoids and Adverse Convulsive Effects: A Pharmacovigilance and Addictovigilance Analysis of Cases Reported in France.

Laroche, Marie-Laure · 2025

130 seizure cases among 4,296 cannabinoid reports (3%).

National Multicenter Cohort Study: Adjunctive Cannabidiol-Enriched Cannabis Oil for Pediatric Drug-Resistant Epilepsy Treatment in Thailand.

Lusawat, Apasri · 2025

Among 101 pediatric patients who had failed an average of 7 antiseizure medications, CBD-enriched oil at a median dose of 6 mg/kg/day produced consistent improvements in 50%+ seizure reduction rates at 3, 6, 9, 12 months and latest follow-up.

Practical approach to the safe use of cannabidiol in patients with refractory epilepsy: a mini review.

Navarro, Cristian E · 2025

While CBD's efficacy for certain severe epilepsy syndromes is established (Dravet, Lennox-Gastaut), the practical details of prescribing it safely remain challenging.

Long-term efficacy and safety of cannabidiol in patients with treatment-resistant focal epilepsies treated in the Expanded Access Program.

Patel, Anup D · 2025

CBD treatment was associated with median reductions of 51-87% in focal seizures and 44-87% in total seizures in the TSC group, and 46-75% and 45-71% in the non-TSC group, sustained through 144 weeks.

Caregiver-reported non-seizure and seizure outcomes with cannabidiol and clobazam in patients aged ≥2 years with Lennox-Gastaut syndrome or Dravet syndrome: A subgroup analysis of the BECOME survey.

Perry, M Scott · 2025

Caregivers reported improvements across multiple domains: seizure frequency (87%), severity (81%), alertness/cognition/executive function (84%), language/communication in non-verbal patients (81%) and verbal patients (76%), emotional/social functioning (79%), daily activities (56%), physical functioning (44%), and sleep (56%).

Real-world efficacy and safety of cannabidiol in developmental and epileptic encephalopathies.

Perulli, Marco · 2025

Clinical trials establish whether a drug works under ideal conditions.

Use of Medicinal Cannabis for Epilepsy in the Australian Community 2023-2024: A Cross-Sectional Survey.

Skene, Douglas A D · 2025

Among 102 people with epilepsy, 27.5% used only illicit cannabis, 27.5% had transitioned to prescribed products, and 16.7% used both.

Medical cannabis utilization in children - a study based on a nationwide cohort.

Treves, Nir · 2025

Parents reported satisfaction in 73% of cases.

Is highly purified cannabidiol a treatment opportunity for drug-resistant epilepsy in subjects with typical Rett syndrome and CDKL5 deficiency disorder?

Vignoli, Aglaia · 2025

CBD reduced seizure frequency in 18 of 27 patients (66.6%) with drug-resistant epilepsy due to Rett syndrome or CDKL5 deficiency.

Cannabinoid-like compounds found in non-cannabis plants exhibit antiseizure activity in genetic mouse models of drug-resistant epilepsy.

Yip, Ka Lai · 2025

Magnolol reduced seizures in both Dravet (Scn1a+/-) and Lennox-Gastaut (Gabrb3+/D120N) mouse models and had excellent brain penetration (brain-to-plasma ratio 7.56).

Endocannabinoid signaling in epilepsy.

Zeng, Chudai · 2025

The endocannabinoid system serves dual roles in epilepsy: restoring excitatory-inhibitory balance to prevent excessive neuronal firing, and alleviating neuroinflammation that contributes to seizure generation and disease progression..

The efficacy and safety of cannabidiol (CBD) in pediatric patients with Dravet Syndrome: a narrative review of clinical trials.

Aderinto, Nicholas · 2024

Across 10 clinical trials, CBD demonstrated efficacy in reducing seizure frequency in children with Dravet syndrome.

Caregiver-reported outcomes with real-world use of cannabidiol in Lennox-Gastaut syndrome and Dravet syndrome from the BECOME survey.

Berg, Anne T · 2024

Caregivers reported improvements in seizure frequency (85%), seizure severity (76%), and seizure-free days (67%).

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

Calonge, Quentin · 2024

No significant difference in responder rates (greater than 50% seizure reduction) between authorized-indication patients (31.3%) and off-label patients (35.6%, p=0.85).

High-purified cannabidiol efficacy and safety in a cohort of adult patients with various types of drug-resistant epilepsies.

Perriguey, M · 2024

Among 73 patients (51 with epileptic encephalopathies, 22 with focal/multifocal epilepsy), 29.4% and 22.7% respectively were responders during follow-up, with no significant difference between groups (P=0.552).

Real-Life Experience With Purified Cannabidiol Treatment for Refractory Epilepsy: A Multicenter Retrospective Study.

Tzadok, Michal · 2024

92.2% of patients had reduced seizure frequency after starting purified CBD.

Consensus panel recommendations for the optimization of EPIDIOLEX® treatment for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex.

Wechsler, Robert T · 2024

Key recommendations include individualizing starting dose and titration rate based on baseline variables and prior medication responses, differentiating Epidiolex from non-approved CBD products, managing drug-drug interactions (particularly with clobazam and valproate), and tracking maximum tolerated dose as a measure of effectiveness..

Retrospective chart review study of use of cannabidiol (CBD) independent of concomitant clobazam use in patients with Lennox-Gastaut syndrome or Dravet syndrome.

Nabbout, Rima · 2023

Among 107 patients (92 LGS, 15 DS) receiving CBD without clobazam for at least 3 months, median seizure frequency change ranged from -6.2% to -20.9% for LGS and 0% to -16.7% for DS over 3-month intervals.

Cannabis-based magistral formulation is highly effective as an adjuvant treatment in drug-resistant focal epilepsy in adult patients: an open-label prospective cohort study.

Navarro, Cristian Eduardo · 2023

Among 44 patients who completed 3+ months of follow-up, median monthly seizures dropped from 11 to 2.5 (p < significant).

A systematic review of cannabidiol trials in neurodevelopmental disorders.

Parrella, Nina-Francecsa · 2023

Nine RCTs across ADHD, autism, intellectual disability, Tourette's, and complex motor disorders showed some positive signals but inconsistent results.

Concomitant cannabidiol does not impact safety and effectiveness of diazepam nasal spray for seizure clusters: Post hoc analysis of a phase 3 safety study.

Peters, Jurriaan M · 2023

Of 163 patients, 73% received no CBD, 14.1% received purified CBD (Epidiolex), and 12.9% received other CBD.

Real-world experience with cannabidiol as add-on treatment in drug-resistant epilepsy.

Vicino, Walter · 2023

In routine clinical practice, CBD produced clinically meaningful seizure reduction (>30%) in a substantial proportion of patients.

Long-term use of cannabidiol-enriched medical cannabis in a prospective cohort of children with drug-resistant developmental and epileptic encephalopathy.

Caraballo, Roberto · 2022

After a median 20 months of treatment, 78% of children had ≥50% seizure reduction and 47.5% had >75% reduction.

Variability in Serum Concentrations and Clinical Response in Artisanal Versus Pharmaceutical Cannabidiol Treatment of Pediatric Pharmacoresistant Epilepsy.

Cohen, Nathan T · 2022

Mean serum CBD was 124 ng/mL for pharmaceutical CBD vs.

Review: Cannabinoids as Medicinals.

Khalsa, Jag H · 2022

Current research shows CBD and other cannabinoids are not ready for formal indications as medicines to treat the wide range of conditions promoted, except for limited use of CBD for two rare forms of childhood epilepsy and CBD combined with THC for MS-associated spasticity..

Effects of Cannabidiol on Adaptive Behavior and Quality of Life in Pediatric Patients With Treatment-Resistant Epilepsy.

Kim, Se Hee · 2022

26.8% of patients achieved 50% or greater seizure reduction after six months of CBD.

An Open Retrospective Study of a Standardized Cannabidiol Based-Oil in Treatment-Resistant Epilepsy.

Marchese, Francesca · 2022

Among 37 patients with treatment-resistant epilepsy of various causes, 7 (19%) became seizure-free and 27 (73%) reported more than 50% seizure reduction at 40-month follow-up.

The Long-Term Effectiveness and Safety of Cannabidiol-Enriched Oil in Children With Drug-Resistant Epilepsy.

Tzadok, Michal · 2022

73.3% of 114 patients reported some seizure improvement.

Outcomes from a Spanish Expanded Access Program on cannabidiol treatment in pediatric and adult patients with epilepsy.

Villanueva, Vicente · 2022

44.9% of patients had at least 50% seizure reduction at 6 months, 38.9% at 12 months.

From an Alternative Medicine to a New Treatment for Refractory Epilepsies: Can Cannabidiol Follow the Same Path to Treat Neuropsychiatric Disorders?

Bitencourt, Rafael M · 2021

Strong evidence supports CBD's anticonvulsant properties for epilepsy, and accumulating research suggests promising effects for depression, anxiety, PTSD, addiction, neurodegenerative disorders, and autism.

Cost-Effectiveness of Medicinal Cannabis for Management of Refractory Symptoms Associated With Chronic Conditions: A Systematic Review of Economic Evaluations.

Erku, Daniel · 2021

Twelve cost-utility analyses were identified across MS (n=8), pediatric epilepsies (n=2), and chronic pain (n=2).

Interaction of cannabidiol with other antiseizure medications: A narrative review.

Gilmartin, Christopher G S · 2021

CBD has potential pharmacokinetic interactions with brivaracetam, clobazam, eslicarbazepine, lacosamide, gabapentin, oxcarbazepine, phenobarbital, potassium bromide, pregabalin, rufinamide, sirolimus/everolimus, stiripentol, tiagabine, topiramate, and zonisamide.

Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome.

Iannone, Luigi Francesco · 2021

At 3 months, 40.2% of patients achieved 50% or greater seizure reduction, with 1.2% becoming seizure-free.

Effect of Cannabidiol on Interictal Epileptiform Activity and Sleep Architecture in Children with Intractable Epilepsy: A Prospective Open-Label Study.

Klotz, Kerstin A · 2021

Interictal epileptiform discharge (IED) rate dropped significantly from 36.8 to 19.6 per minute after 3 months of CBD (p<0.0001).

Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox-Gastaut Syndrome.

Lattanzi, Simona · 2021

Beyond its approved indications (DS, LGS, TSC), purified CBD showed effectiveness in open-label studies for CDKL5 deficiency disorder, Aicardi syndrome, Dup15q syndrome, Doose syndrome, SYNGAP1 encephalopathy, and epilepsy with myoclonic absences.

Cross-sectional and longitudinal evaluation of cannabidiol (CBD) product use and health among people with epilepsy.

Strickland, Justin C · 2021

Artisanal CBD users showed significantly better quality of life, lower psychiatric symptom severity, improved sleep, better medication tolerability, fewer prescription medications, and reduced healthcare utilization compared to controls, both cross-sectionally and longitudinally when participants initiated CBD use..

Cannabidiol-enriched oil in children and adults with treatment-resistant epilepsy-does tolerance exist?

Uliel-Sibony, Shimrit · 2021

Of 84 patients analyzed for tolerance (treated at least 3 months), 21 (25%) developed tolerance after a mean of 7.3 months.

Cannabidiol treatment of severe refractory epilepsy in children and young adults.

Zilmer, Monica · 2021

At 3 months, 31.4% of patients achieved 50% or greater seizure reduction and 68.6% showed some improvement.

Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop-seizure frequency.

Bergmann, Kirsten Riber · 2020

Simulations showed that the observed seizure reduction from CBD could be replicated by assuming: (1) patients on clobazam had a 2- to 7-fold increase in norclobazam (active metabolite) exposure, and (2) patients not on clobazam had seizure reduction and variability similar to placebo.

Effectiveness of cannabidiol in a prospective cohort of children with drug-resistant epileptic encephalopathy in Argentina.

Caraballo, Roberto · 2020

Of 49 children followed for 3-12 months, 80% responded to CBD add-on therapy.

A perspective on cannabinoids for treating epilepsy: Do they really change the landscape?

Cross, J Helen · 2020

Only purified CBD formulations have been rigorously evaluated in controlled trials, showing modest but significant improvements in motor seizures.

Slow Titration of Cannabidiol Add-On in Drug-Resistant Epilepsies Can Improve Safety With Maintained Efficacy in an Open-Label Study.

D'Onofrio, Gianluca · 2020

At 6 months, mean seizure frequency decreased 41% from baseline, and 37.8% had 50%+ seizure reduction.

Barriers in accessing medical cannabis for children with drug-resistant epilepsy in Canada: A qualitative study.

Elliott, Jesse · 2020

Most parents encountered resistance from their child's neurologist when seeking medical cannabis authorization, forcing many to seek authorization through cannabis clinics instead of their existing care team..

Cannabinoids for People with ASD: A Systematic Review of Published and Ongoing Studies.

Fusar-Poli, Laura · 2020

Cannabinoids improved some autism-associated symptoms including problem behaviors, sleep problems, and hyperactivity, with limited side effects.

Anticonvulsive Properties of Cannabidiol in a Model of Generalized Seizure Are Transient Receptor Potential Vanilloid 1 Dependent.

Gray, Royston A · 2020

CBD at 50 and 100 mg/kg significantly raised seizure thresholds in wildtype mice but not in TRPV1 knockout mice.

Cannabidiol for Treating Lennox-Gastaut Syndrome and Dravet Syndrome in Korea.

Koo, Chung Mo · 2020

Among 34 Lennox-Gastaut and 10 Dravet syndrome patients (ages 1-16), CBD at 10 mg/kg/day produced 50%+ seizure reduction in 32.3% of LGS patients at 3 months (declining to 20.6% at 6 months) and 30% of DS patients at 3 months (20% at 6 months).

Long-term efficacy and safety of cannabidiol (CBD) in children with treatment-resistant epilepsy: Results from a state-based expanded access program.

Park, Yong D · 2020

Over 36 months, 45 children with treatment-resistant epilepsy (various etiologies beyond Dravet/LGS) treated with adjunctive CBD (Epidiolex, up to 50 mg/kg/day) showed statistically significant reductions in seizure frequency at months 3, 6, 12, 18, 24, and 36.

A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models.

Perry, Christopher J · 2020

Using the model organism Dictyostelium, researchers identified that CBD activity depends partly on the glycine cleavage system, linked to folate one-carbon metabolism (FOCM).

Attitudes and knowledge about cannabis and cannabis-based therapies among US neurologists, nurses, and pharmacists.

Szaflarski, Magdalena · 2020

Over 80% supported medical cannabis use and legalization, especially CBD for epilepsy when prescribed by a provider.

Abrupt withdrawal of cannabidiol (CBD): A randomized trial.

Taylor, Lesley · 2020

After four weeks of 1,500 mg daily CBD, volunteers randomized to abrupt discontinuation showed no increase in withdrawal scores.

Cognitive function and adaptive skills after a one-year trial of cannabidiol (CBD) in a pediatric sample with treatment-resistant epilepsy.

Thompson, Matthew D · 2020

Among 38 pediatric patients (ages 3-19) with treatment-resistant epilepsy, those who completed cognitive testing showed no significant changes after one year of CBD.

Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions.

Anderson, Lyndsey L · 2019

CBD potently inhibited liver enzymes (CYP3A4, CYP2C19) that metabolize clobazam and its metabolite, increasing plasma clobazam levels.

Cannabis and Neuropsychiatric Disorders: An Updated Review.

Chayasirisobhon, Sirichai · 2019

CBD has demonstrated therapeutic benefit across multiple neuropsychiatric conditions including autism spectrum disorder, anxiety, psychosis, neuropathic pain, cancer pain, migraine, MS, Alzheimer disease, Parkinson disease, Huntington disease, hypoxic-ischemic injury, and epilepsy.

Effects of cannabidiol (CBD) in neuropsychiatric disorders: A review of pre-clinical and clinical findings.

Elsaid, Sonja · 2019

CBD is safe, well-tolerated, and efficacious for several seizure disorders.

Drug-drug interactions between antiepileptics and cannabinoids.

Miziak, Barbara · 2019

In animal models, WIN 55,212-2 (CB1/CB2 agonist) potentiated anticonvulsant activity of various AEDs but caused profound neurotoxicity when combined with conventional AEDs.

Cannabidiol: A Review of Clinical Efficacy and Safety in Epilepsy.

Samanta, Debopam · 2019

CBD modulates multiple endogenous systems for anticonvulsant effects.

Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US.

Sands, Tristan T · 2019

Seven of 26 children (26.9%) achieved sustained >50% seizure reduction, including 3 (11.5%) who became seizure-free.

A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis.

Berman, Paula · 2018

Researchers developed a new analytical method to profile 94 individual phytocannabinoids across 10 different subclasses in 36 of the most commonly prescribed medical cannabis strains in Israel.

Cannabinoids for epilepsy: What do we know and where do we go?

Brodie, Martin J · 2018

The authors reviewed the rapidly evolving field of cannabinoids for epilepsy, noting several important developments and remaining challenges. Recent randomized placebo-controlled trials confirmed CBD's efficacy in two severe childhood epilepsy syndromes: Dravet syndrome and Lennox-Gastaut syndrome.

Efficacy of CBD-enriched medical cannabis for treatment of refractory epilepsy in children and adolescents - An observational, longitudinal study.

Hausman-Kedem, Moran · 2018

Researchers followed 57 patients aged 1-20 years with epilepsy of various causes who were treated with CBD-enriched cannabis oil (CBD:THC ratio of 20:1) for at least 3 months, with a median follow-up of 18 months. Of 46 patients included in efficacy analysis, 26 (56%) achieved at least 50% reduction in mean monthly seizure frequency. Response rates did not differ significantly by epilepsy type or cannabis strain used.

A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome.

McCoy, Bláthnaid · 2018

Twenty children with Dravet syndrome received add-on therapy with TIL-TC150, a cannabis oil containing 100 mg/mL CBD and 2 mg/mL THC. Doses ranged from 2-16 mg/kg/day of CBD (mean achieved: 13.3 mg/kg/day) and 0.04-0.32 mg/kg/day of THC (mean: 0.27 mg/kg/day). Nineteen of 20 participants completed the 20-week intervention. Results showed a median motor seizure reduction of 70.6%, with 63% of patients achieving at least 50% seizure reduction. There was a statistically significant improvement in quality of life and reduction in EEG spike activity. Adverse events during titration included somnolence, anorexia, and diarrhea.

Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis.

Pamplona, Fabricio A · 2018

Researchers pooled data from 11 observational studies involving 670 patients with treatment-resistant epilepsy to compare CBD-rich extracts to purified CBD products. Overall, 64% of patients (399/622) reported seizure improvement. CBD-rich extracts were associated with significantly better outcomes: - 71% improvement rate (318/447) vs 46% for purified CBD (81/175), p < 0.0001. - Lower average dose needed: 6.0 mg/kg/day vs 25.3 mg/kg/day. - Fewer mild adverse effects: 33% vs 76%, p < 0.0001. - Fewer severe adverse effects: 2.2% vs 12.6%, p < 0.0001 (note: rates of severe AEs with purified CBD corrected). The authors attributed the difference to synergistic effects of CBD with other phytocompounds (the entourage effect), though they noted this needs confirmation in controlled trials..

Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center.

Porcari, Giulia S · 2018

Researchers reviewed records of 108 pediatric epilepsy patients using artisanal CBD oil preparations at a tertiary medical center. 39% of patients achieved greater than 50% seizure reduction, with 10% becoming seizure-free. No patients achieved CBD monotherapy, but AED weaning became possible in 22% of patients. Patients also taking clobazam had a slightly higher response rate (44% vs 33% without clobazam), but this difference was not statistically significant. Sedation was the most common side effect, occurring in less than 4% of patients, all of whom were also taking clobazam. Notably, 14% of patients showed increased alertness and improved verbal interactions, a positive cognitive effect. Benefits were more marked in the CBD-alone group compared to CBD + clobazam, but this difference was also not statistically significant..

Investigational cannabinoids in seizure disorders, what have we learned thus far?

Ružić Zečević, Dejana · 2018

Preclinical studies confirmed anticonvulsant activity of CBD and CBDV across multiple epilepsy models.

Cannabinoid-Based Therapies and Brain Development: Potential Harmful Effect of Early Modulation of the Endocannabinoid System.

Schonhofen, Patrícia · 2018

The endocannabinoid system regulates progenitor cell fate, neural differentiation, migration, and survival from early developmental stages.

Cannabis cultivation: Methodological issues for obtaining medical-grade product.

Chandra, Suman · 2017

The review described the production practices of two institutions with extensive cannabis cultivation experience.

Cannabinoids therapeutic use: what is our current understanding following the introduction of THC, THC:CBD oromucosal spray and others?

Maccarrone, Mauro · 2017

This expert review assessed the state of cannabinoid therapeutics roughly five years after THC/CBD oromucosal spray (Sativex) entered clinical practice for multiple sclerosis spasticity. For MS spasticity, clinical trials confirmed the spray's efficacy and tolerability, establishing it as the most widely used prescription cannabinoid medicine internationally.

Evidence for the use of "medical marijuana" in psychiatric and neurologic disorders.

Noel, Christopher · 2017

This review took a deliberately narrow approach, examining only randomized clinical trials of phytocannabinoids (plant-derived cannabis) for psychiatric and neurologic conditions, excluding synthetic products like dronabinol and nabilone. The search identified trials in dementia, multiple sclerosis, Parkinson's disease, Huntington's disease, schizophrenia, social anxiety disorder, depression, tobacco use disorder, and neuropathic pain. The overall evidence base was thin.

An Australian nationwide survey on medicinal cannabis use for epilepsy: History of antiepileptic drug treatment predicts medicinal cannabis use.

Suraev, Anastasia S · 2017

Epilepsy Action Australia surveyed 976 people with epilepsy nationwide.

Duration of use of oral cannabis extract in a cohort of pediatric epilepsy patients.

Treat, Lauren · 2017

A retrospective review of 119 pediatric epilepsy patients using oral cannabis extracts (OCEs) revealed high rates of discontinuation.

Pediatric Concerns Due to Expanded Cannabis Use: Unintended Consequences of Legalization.

Wang, George Sam · 2017

The review identified cannabis legalization's impact on children across four developmental stages. Prenatal: Cannabis remains one of the most commonly used substances during pregnancy, with increasing use as legalization normalizes cannabis.

Medical Cannabinoids in Children and Adolescents: A Systematic Review.

Wong, Shane Shucheng · 2017

Researchers systematically reviewed 2,743 citations from medical databases and identified 22 studies involving 795 children and adolescents who received cannabinoid treatments.

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

Devinsky, Orrin · 2016

This landmark open-label trial enrolled 214 patients (aged 1-30 years) with severe, treatment-resistant epilepsy across 11 US epilepsy centers.

Is the medical use of cannabis a therapeutic option for children?

Rieder, Michael J · 2016

This clinical review examined the evidence for medical cannabis use in children, prompted by case reports of children with refractory epilepsy responding to cannabis-based treatments.

CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience.

Tzadok, Michal · 2016

Researchers reported the experience of five Israeli pediatric epilepsy centers treating 74 children and adolescents (ages 1-18) with intractable epilepsy using CBD-enriched medical cannabis oil (20:1 CBD to THC ratio dissolved in olive oil). These children had severe, treatment-resistant epilepsy: all had failed more than 7 antiepileptic drugs, and 66% had also failed a ketogenic diet, vagal nerve stimulator, or both.

Narrative review of the safety and efficacy of marijuana for the treatment of commonly state-approved medical and psychiatric disorders.

Belendiuk, Katherine A · 2015

Researchers reviewed the scientific evidence for cannabis treatment across the conditions most commonly approved by state medical marijuana programs.

Medical marijuana in neurology.

Benbadis, Selim R · 2014

This expert review assessed the evidence for cannabinoids in neurological diseases.

The case for assessing cannabidiol in epilepsy.

Cilio, Maria Roberta · 2014

This editorial-style review from leading epilepsy researchers argued that pure CBD had accumulated sufficient preclinical evidence to justify systematic clinical investigation for treatment-resistant epilepsy.

Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.

Devinsky, Orrin · 2014

This landmark review by leading researchers summarized the evidence for CBD across multiple neuropsychiatric conditions.

Therapeutic potential of cannabinoid medicines.

Robson, P J · 2014

The review covers the endocannabinoid system's role in immune response, appetite, cognition, emotion, perception, motor coordination, body temperature, sleep, and bone metabolism.

Cannabis, cannabidiol, and epilepsy--from receptors to clinical response.

Szaflarski, Jerzy P · 2014

The review covers three key areas.

Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.

Pertwee, Roger G · 2012

Three cannabinoid medicines were already in clinical use at the time: Cesamet (nabilone), Marinol (dronabinol), and Sativex (THC with CBD).

Cannabidiol in humans-the quest for therapeutic targets.

Zhornitsky, Simon · 2012

The review identified 34 studies: 16 in healthy subjects and 18 in clinical populations covering MS, schizophrenia, bipolar mania, social anxiety, pain, cancer, Huntington's disease, insomnia, and epilepsy. Key findings included: high inhaled/IV doses of CBD were needed to block THC effects.

Medicinal cannabis: is delta9-tetrahydrocannabinol necessary for all its effects?

Wilkinson, J D · 2003

In a mouse model of MS, whole cannabis extract (SCE) and pure THC inhibited spasticity to comparable levels, but the extract produced faster onset of muscle relaxation and shorter time to maximum effect.

Cannabinoid Therapies in Less-Common Disorders: Clinical Evidence and Formulation Strategies.

Afonso, Silvia · 2026

Recent evidence supports cannabinoid use in rare epilepsies beyond Dravet/Lennox-Gastaut, movement disorders, and rare skin diseases, while Fragile X syndrome trials revealed methodological challenges instructive for future research..

Cannabidiol against Epilepsy: Insights and an Experimental In Silico Approach.

Dos Santos, Aline Matilde Ferreira · 2026

This study used computational (in silico) methods to model how CBD might interact with five types of brain receptors implicated in epilepsy: T-type calcium channels (CaV), GABA-A receptors, KCNQ2 potassium channels, voltage-gated sodium channels (NaV), and AMPA receptors. Pharmacodynamic analysis showed CBD has good oral absorption characteristics and the ability to cross the blood-brain barrier, as indicated by its pharmacokinetic parameters.

Influence of cannabis use on length of stay in patients admitted to the epilepsy monitoring unit.

Hoerth, Oliver · 2026

Cannabis use was associated with 0.9-day shorter length of stay and 18.1% higher event capture rate in the EMU, alongside significantly higher rates of psychosocial comorbidities: 12.6% physical abuse, 11.1% sexual abuse, 10.2% mental abuse, 18.9% higher MDD rates, and 22.1% higher GAD rates..

Cannabinoids and drug-drug pharmacokinetic interactions: Deciphering the risks.

Papakyriakopoulou, Paraskevi · 2026

This review mapped the pharmacokinetic drug-drug interactions involving cannabinoids across the full ADME framework (absorption, distribution, metabolism, excretion). The metabolism interactions are the most clinically significant.

Antiseizure Effects of Cannabidiol in Combination With Cannabigerol in the Maximal Electroshock Seizure Model.

Zhou, Han Zhong · 2026

Current antiseizure therapy fails for about 30% of epilepsy patients.

Protective Role of CBD Against Nicotine Pouch-Induced Seizure Aggravation and Alterations in Brain Glymphatic Biomarkers.

Bhandari, Bidhan · 2025

Seven days of nicotine pouch exposure significantly worsened seizure severity, raised brain inflammation markers (IL-6, HMGB1), and impaired the brain's waste-clearance system in mice.

Efficacy and safety of cannabidiol in a single-center pediatric drug-resistant epilepsy cohort: a retrospective study.

Butera, Ambra · 2025

11 of 15 patients showed seizure frequency reduction: 7 were responders (over 50% reduction, including 2 seizure-free) and 4 were partial responders (30-50% reduction).

Cannabidiol dampens propagation of hippocampal hyperactivity and differentially modulates feedforward and feedback inhibition.

Chamberland, Simon · 2025

CBD caused a GPR55-dependent reduction in CA3-to-CA1 hippocampal activity propagation by increasing PV interneuron recruitment while reducing SST interneuron activity; this effect was mimicked by GPR55 antagonism and PV interneuron enhancement..

The Current State of Unapproved Cannabidiol Product Use in Children.

Cowell, Braden · 2025

CBD has one FDA-approved pediatric use: Epidiolex for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex.

Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentylenetetrazole.

de Aquino, Pedro Everson Alexandre · 2025

In acute seizure tests, CBD and THC at 3-10 mg/kg and their 1:1 combinations increased latency to generalized seizures and improved survival.

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

Di Mauro, Giovanni · 2025

Both patients achieved resolution of status epilepticus after adding highly purified CBD (hpCBD) as add-on therapy via nasogastric tube, without adverse events.

Carvone derived cannabidiol enantiomers as novel anticonvulsants.

Hines, Rochelle M · 2025

Natural CBD (marketed as Epidiolex) works for certain severe childhood epilepsy syndromes, but its effectiveness is limited and it carries regulatory complexity as a cannabis-derived product.

Medical Cannabis and Epilepsy: The Evidence.

Kaur, Varinder · 2025

This review summarizes the state of evidence for cannabis-based treatments in epilepsy, focusing on the two main phytocannabinoids: cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). The clinical need is real: roughly 30% of epilepsy patients have seizures that resist available medications.

Cannabidiol ameliorates seizures and neuronal damage in ferric chloride-induced posttraumatic epilepsy by targeting TRPV1 channel.

Ma, Lin · 2025

CBD reduced seizure severity, decreased EEG amplitude and total power, and lowered spike wave discharges in a ferric chloride-induced post-traumatic epilepsy model.

Preclinical assessment of pharmacokinetics and anticonvulsant activity of CBDTech, a novel orally administered cannabidiol (CBD) formulation for seizure and epilepsy.

McDonald, Jacob D · 2025

One of CBD's biggest pharmacological limitations is poor oral bioavailability—most of what you swallow gets destroyed by the liver before reaching the bloodstream (first-pass metabolism).

Epilepsy, neuroinflammation and cannabidiol What do we know thus far?

Pesántez Ríos, Gabriela · 2025

One of the challenges in understanding CBD's anti-seizure action is that it doesn't work through a single, clean mechanism the way most drugs do.

Cannabidiol potentiates phenobarbital effects in the control of pentylenetetrazole (PTZ)-induced epileptic seizures in neonate rats.

Pinto, Lillian Soares · 2025

Low CBD doses (3 and 30 mg/kg) had limited antiseizure effects alone, while higher doses (100 and 200 mg/kg) modestly reduced seizures.

Status Epilepticus After an Exploratory Ingestion of Cannabis Edibles.

Rivera, Kevin · 2025

An 18-month-old male presented with generalized tonic-clonic seizures that recurred despite multiple benzodiazepine doses, requiring intubation and mechanical ventilation.

The DEC2-SCN2A Axis is Essential for the Anticonvulsant Effects of Cannabidiol by Modulating Neuronal Plasticity.

Song, Huifang · 2025

DEC2 acts as a transcriptional repressor of SCN2A by binding to class B E-boxes in its promoter.

Cannabidiol attenuates epileptic phenotype and increases survival in a mouse model of developmental and epileptic encephalopathy type 1.

Verrillo, Lucia · 2025

Daily CBD (100 mg/kg) for 7 days reduced the severity and frequency of spontaneous recurrent seizures and significantly extended lifespan in Arx(GCG)7/Y mice.

Drug-Cannabinoid Interactions in Selected Therapeutics for Symptoms Associated with Epilepsy, Autism Spectrum Disorder, Cancer, Multiple Sclerosis, and Pain.

Campos, Maria G · 2024

As medical cannabis use expands, patients are increasingly combining cannabinoids with prescription medications for serious conditions.

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

Mannini, Elisa · 2024

Off-label cannabidiol produced significant seizure frequency reduction in a patient with a rare genetic DEE not covered by current CBD indications.

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

Massey, Sean · 2024

CBD is proven for LGS, Dravet, and TSC.

Medical cannabis and cannabidiol: A new harvest for Malawi.

Bandawe, Gama · 2022

CBD has an established role in treating epilepsy (FDA-approved Epidiolex) and emerging evidence for antipsychotic and neuroprotective properties, with the authors proposing potential adjunctive use for neuropsychological complications of malaria..

Dissociable changes in spike and wave discharges following exposure to injected cannabinoids and smoked cannabis in Genetic Absence Epilepsy Rats from Strasbourg.

Roebuck, Andrew J · 2022

Absence epilepsy causes brief seizure episodes (staring spells) characterized by distinctive spike-and-wave discharges (SWDs) on EEG.

Behavioral and Molecular Responses to Exogenous Cannabinoids During Pentylenetetrazol-Induced Convulsions in Male and Female Rats.

Zirotti Rosenberg, Antonella · 2022

WIN prevented convulsions of medium severity in both female and male rats.

Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy.

Anderson, Lyndsey L · 2021

Screening identified CBGA, CBDVA, and CBGVA as novel anticonvulsants.

Cannabidiol-enriched medical cannabis as add-on therapy in children with treatment-resistant West syndrome: A study of eight patients.

Caraballo, Roberto · 2021

Of 8 children with treatment-resistant West syndrome treated with CBD:THC (25:1 ratio), 2 had 75-99% seizure reduction, 2 had 50-74% reduction, 3 had less than 50% reduction, and 1 had no change.

The use of medical cannabis in pediatric palliative care: a case series.

Divisic, Antuan · 2021

All six patients experienced a reduction in seizure frequency (with variable extent) after starting medical cannabis.

The ω-3 endocannabinoid docosahexaenoyl ethanolamide reduces seizure susceptibility in mice by activating cannabinoid type 1 receptors.

Ghanbari, Mohammad-Mahdi · 2021

DHEA (100-300 uM) significantly increased seizure threshold within 10 minutes, more potently than its parent molecule DHA (which required 300 uM and 15 minutes).

Family attitudes about and experiences with medical cannabis in children with cancer or epilepsy: an exploratory qualitative study.

Gibbard, Marissa · 2021

Five themes emerged: 1) parents sought cannabis as a last resort for severely ill children; 2) information came from social media, industry, and other families rather than healthcare providers; 3) cannabis was viewed ambiguously as both a serious drug needing medical oversight and a safe natural product; 4) parents perceived medical benefits with few adverse effect concerns; 5) high costs and uncertain legality were barriers but did not stop use..

Cannabidiolic acid exhibits entourage-like improvements of anticonvulsant activity in an acute rat model of seizures.

Goerl, Brett · 2021

In the maximal electroshock seizure test, Chylobinoid (CBDa plus minor cannabinoids) had an ED50 of 76.7 mg/kg, Mg-CBDa (purified) had an ED50 of 115.4 mg/kg, and CBD had an ED50 of 68.8 mg/kg.

Two-center experience of cannabidiol use in adults with Dravet syndrome.

Silvennoinen, Katri · 2021

Among 17 evaluable adults with Dravet syndrome treated with CBD (up to 20 mg/kg), 3 (17.6%) achieved greater than 30% reduction in convulsive seizures (range 87.5-100%), while adverse effects occurred in all patients, with transaminitis in 52.9% and behavioral side effects leading to discontinuation in 16.7%..

Global brain network dynamics predict therapeutic responsiveness to cannabidiol treatment for refractory epilepsy.

Anderson, David E · 2020

Patients who achieved >70% seizure reduction (responders) showed increased network integration (higher global efficiency, lower degree) and increased segregation (higher modularity) in the beta frequency band compared to non-responders.

Interactions between cannabidiol and Δ9 -tetrahydrocannabinol in modulating seizure susceptibility and survival in a mouse model of Dravet syndrome.

Anderson, Lyndsey L · 2020

CBD (100 mg/kg) alone was anticonvulsant against heat-induced seizures.

Cannabinoid receptors and the proconvulsant effect of toxoplasmosis in mice.

Ghanbari, Mohammad-Mahdi · 2020

The CB1 agonist ACEA, the endocannabinoid-boosting agent JZL184, and the CB2 antagonist AM630 all raised seizure thresholds in both healthy and Toxoplasma-infected mice.

Safety and pharmacokinetics of medical cannabis preparation in a monocentric series of young patients with drug resistant epilepsy.

Gherzi, Marcella · 2020

The cannabis preparation was generally well tolerated, with adverse events in 6 of 10 patients (mostly GI, sleep, or behavioral issues).

Response to cannabidiol in epilepsy of infancy with migrating focal seizures associated with KCNT1 mutations: An open-label, prospective, interventional study.

Poisson, Kelsey · 2020

Three patients with EIMFS secondary to KCNT1 mutations received pharmaceutical-grade CBD.

A pediatric patient with autism spectrum disorder and epilepsy using cannabinoid extracts as complementary therapy: a case report.

Ponton, Juliana Andrea · 2020

A 15-year-old boy with autism, selective mutism, anxiety, and controlled epilepsy was prescribed CBD-based extract to potentially replace seizure medications.

Effect of Cannabinoids on Electroencephalography of a Child with Lennox-Gastaut Syndrome.

Prakash, Vikram · 2020

A 9-year-old boy with Lennox-Gastaut syndrome of unknown etiology treated with highly purified CBD (Epidiolex) achieved complete seizure control and near-normalization of EEG background activity.

Drug-Drug Interactions Between Cannabidiol and Lithium.

Singh, Rani K · 2020

An autistic patient with LGS and psychiatric comorbidities on multiple medications including lithium developed hypersomnolence, ataxia, and decreased oral intake several weeks after starting CBD.

Full-Spectrum Cannabis Extract Microdepots Support Controlled Release of Multiple Phytocannabinoids for Extended Therapeutic Effect.

Uziel, Almog · 2020

Subcutaneously injected microdepots released CBD and other phytocannabinoids over 14+ days, maintaining elevated serum levels.

Inverse Agonism of Cannabinoid Receptor Type 2 Confers Anti-inflammatory and Neuroprotective Effects Following Status Epileptics.

Yu, Ying · 2020

Status epilepticus downregulated CB1 but slightly upregulated CB2 in the hippocampus.

Cannabinoids Rescue Cocaine-Induced Seizures by Restoring Brain Glycine Receptor Dysfunction.

Zou, Guichang · 2020

Systemic cannabinoid administration alleviated cocaine-induced seizures independently of CB1 and CB2 receptors.

Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats.

Colangeli, Roberto · 2019

WIN55,212-2 (CB1 agonist at 2 mg/kg) and RO60-0175 (5-HT2B/2C agonist at 3 mg/kg) were ineffective alone against EEG seizures but combined they reduced seizure incidence, severity, and increased latency to seizure onset.

Cannabis for refractory epilepsy in children: A review focusing on CDKL5 Deficiency Disorder.

Dale, Tristan · 2019

Evidence supports cannabinoids for refractory epilepsies similar to CDD (Dravet, Lennox-Gastaut syndromes).

Activation of ATP-sensitive K-channel promotes the anticonvulsant properties of cannabinoid receptor agonist through mitochondrial ATP level reduction.

Haj-Mirzaian, Arvin · 2019

WIN 55,212-2 at 10 mg/kg significantly increased clonic seizure threshold via CB1 (blocked by AM-251) but not CB2 (AM-630 had no effect).

Marijuana use among patients with epilepsy at a tertiary care center.

Kerr, Alysse · 2019

87.2% used cannabis to treat epilepsy.

Prospective evaluation of oral cannabis extracts in children with epilepsy.

Knupp, Kelly G · 2019

The 24% responder rate (50%+ seizure reduction) matched placebo rates from formal clinical trials.

The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study.

Mitelpunkt, Alexis · 2019

Median seizure count reduced by 81.9% from baseline.

Purified Cannabidiol for Treatment of Refractory Epilepsies in Pediatric Patients with Developmental and Epileptic Encephalopathy.

Pietrafusa, Nicola · 2019

Eleven of 29 patients (37.9%) achieved 50% or greater seizure reduction.

Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community.

Suraev, A · 2018

There was high variability in cannabinoid content across extracts.

Parent use of cannabis for intractable pediatric epilepsy: Everyday empiricism and the boundaries of scientific medicine.

Sobo, Elisa J · 2017

Twenty-five parents who used, had used, or sought to use cannabis for their children's epilepsy were interviewed about their evidentiary standards, research methods, and aims. Contrary to stereotypes of alternative medicine users rejecting science, these parents generally described their work as experimentation.

Cannabis in epilepsy: From clinical practice to basic research focusing on the possible role of cannabidivarin.

Morano, Alessandra · 2016

A patient with symptomatic partial epilepsy who had failed numerous medications and surgical treatments began self-medicating with cannabis.

Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome.

Hussain, Shaun A · 2015

Researchers surveyed 117 parents who had given CBD-enriched cannabis preparations to their children for epilepsy.

Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy.

Press, Craig A · 2015

Researchers reviewed records of 75 children and adolescents treated with oral cannabis extracts (OCEs) at a single epilepsy center.

Inhibition of monoacylglycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice.

von Rüden, E L · 2015

Researchers tested whether increasing levels of the brain's own cannabinoid 2-AG, by blocking the enzyme MAGL that normally breaks it down, could slow epilepsy development in mice. Using JZL184, a MAGL inhibitor, they found it significantly delayed the progression from mild to generalized seizures in the kindling model of temporal lobe epilepsy.

The case for medical marijuana in epilepsy.

Maa, Edward · 2014

Charlotte, a child with SCN1A-confirmed Dravet syndrome, experienced a dramatic reduction in seizure frequency after beginning adjunctive therapy with Charlotte's Web, a high-CBD/low-THC cannabis strain.

Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy.

Porter, Brenda E · 2013

Nineteen parents of children with treatment-resistant epilepsy (13 with Dravet syndrome, 4 with Doose syndrome, 1 Lennox-Gastaut, 1 idiopathic) were surveyed via a Facebook support group.

Seizure exacerbation in two patients with focal epilepsy following marijuana cessation.

Hegde, Manu · 2012

Two patients with focal epilepsy had well-controlled seizures through regular outpatient marijuana use in addition to their anticonvulsant medications.

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges.

Grant, Igor · 2005

This review examined the endocannabinoid signaling system, including CB1 receptors (heavily represented in the central nervous system), CB2 receptors (localized to immune cells), and their endogenous ligands anandamide and 2-arachidonoyl glycerol. A key insight was that endocannabinoid system activation can enhance or dampen neural circuit activity depending on the circuit's existing state of activation.

The Anticonvulsant Effects of Different Cannabis Extracts in a Zebrafish Model of Epilepsy.

Jackson, Karen · 2025

In a PTZ-induced zebrafish seizure model, 5.7 ug/mL of pure CBD and 10 ug/mL of various cannabis extracts both significantly reduced hyperactivity compared to both PTZ alone and the standard anti-epileptic drug valproic acid.

Cannabinoids Used for Medical Purposes in Children and Adolescents: A Systematic Review and Meta-Analysis.

Chhabra, Manik · 2024

Compared to control, cannabinoids in children increased risk of overall adverse events (RR 1.09), withdrawals due to AEs (RR 3.07), and serious AEs (RR 1.81).

Purified cannabidiol as add-on therapy in children with treatment-resistant infantile epileptic spasms syndrome.

Reyes Valenzuela, Gabriela · 2024

Of 28 infants with treatment-resistant IESS, 7 (25%) became spasm-free and 12 (43%) had >50% spasm reduction (total responder rate 67.8%).

Cannabidiol Add-On in Glycosylphosphatidylinositol-Related Drug-Resistant Epilepsy.

Riva, Antonella · 2024

Six patients with genetically confirmed GPI-anchored protein deficiency and drug-resistant epilepsy received add-on CBD (Epidyolex).

Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis.

Talwar, Ashna · 2023

CBD treatment was significantly more effective than placebo (OR=2.45, 95% CI: 1.81-3.32).

Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial

Thiele EA · 2018

Add-on CBD (20 mg/kg/day) reduced drop seizure frequency by 43.9% versus 21.8% with placebo (p=0.0135) in 171 patients with Lennox-Gastaut syndrome.

Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome

Devinsky O · 2018

CBD pharmacokinetics are dose-proportional in young Dravet patients.

Chronic administration of cannabidiol to healthy volunteers and epileptic patients

Cunha JM · 1980

The first-ever clinical trial of CBD for epilepsy.