CBD reduced seizures by 50% or more in 40% of highly treatment-resistant epilepsy patients

Among 82 patients with severe Dravet or Lennox-Gastaut syndrome who had failed a median of 8 prior medications, 40.2% achieved at least 50% seizure reduction with purified CBD within 3 months.

Iannone, Luigi Francesco et al.·Frontiers in neurology·2021·Moderate EvidenceProspective Cohort
RTHC-03215Prospective CohortModerate Evidence2021RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Prospective Cohort
Evidence
Moderate Evidence
Sample
N=93

What This Study Found

At 3 months, 40.2% of patients achieved 50% or greater seizure reduction, with 1.2% becoming seizure-free. Retention rates were similar for Dravet and Lennox-Gastaut syndromes but higher in adults than pediatric patients. Of 93 enrolled patients, 31.2% dropped out (17.2% for lack of efficacy, 12.9% for adverse events). Most common side effects were somnolence (22.6%) and diarrhea (11.9%).

Key Numbers

93 enrolled, 82 analyzed. Median 8 failed prior medications. 50% seizure reduction: 40.2%. Seizure-free: 1.2%. Dropout: 31.2%. Somnolence: 22.6%. Diarrhea: 11.9%. Transaminase elevation noted. CBD coadministered with valproic acid (62.2%) and clobazam (41.5%).

How They Did This

Open-label prospective expanded access program across 30 Italian centers (December 2018 to December 2019). Purified CBD up to 25 mg/kg/day added to existing medications. 93 patients enrolled for safety analysis, 82 with at least 3 months follow-up for effectiveness. Median 8 previously failed antiseizure medications.

Why This Research Matters

These patients represent the most treatment-resistant cases, having failed a median of 8 medications. Achieving 50% seizure reduction in 40% of this population is clinically meaningful, and the real-world expanded access design provides pragmatic evidence beyond controlled trials.

The Bigger Picture

This Italian EAP adds to the global evidence supporting CBD for treatment-resistant epilepsy. The finding that effectiveness was independent of clobazam use is important, as some have questioned whether CBD benefits in epilepsy are partly mediated through clobazam interactions.

What This Study Doesn't Tell Us

Open-label design with no placebo group. Potential placebo effect. Only 3 months of effectiveness data. Concurrent medication changes possible. Dropout rate of 31% may bias results.

Questions This Raises

  • ?Do seizure reduction rates improve or decline beyond 3 months?
  • ?Which patients are most likely to respond?
  • ?Is the benefit maintained when adjusting concurrent medications?

Trust & Context

Key Stat:
40.2% achieved ≥50% seizure reduction after failing median 8 prior drugs
Evidence Grade:
Multicenter prospective design in a real-world setting, but open-label with no placebo control.
Study Age:
2021 interim results from Italian expanded access program (2018-2019).
Original Title:
Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome.
Published In:
Frontiers in neurology, 12, 673135 (2021)
Authors:
Iannone, Luigi Francesco, Arena, Gabriele, Battaglia, Domenica(2), Bisulli, Francesca, Bonanni, Paolo, Boni, Antonella, Canevini, Maria Paola, Cantalupo, Gaetano, Cesaroni, Elisabetta, Contin, Manuela, Coppola, Antonietta, Cordelli, Duccio Maria, Cricchiuti, Giovanni, De Giorgis, Valentina, De Leva, Maria Fulvia, De Rinaldis, Marta, d'Orsi, Giuseppe, Elia, Maurizio, Galimberti, Carlo Andrea, Morano, Alessandra, Granata, Tiziana, Guerrini, Renzo, Lodi, Monica A M, La Neve, Angela, Marchese, Francesca, Masnada, Silvia, Michelucci, Roberto, Nosadini, Margherita, Pilolli, Nicola, Pruna, Dario, Ragona, Francesca, Rosati, Anna, Santucci, Margherita, Spalice, Alberto, Pietrafusa, Nicola, Striano, Pasquale, Tartara, Elena, Tassi, Laura, Papa, Amanda, Zucca, Claudio, Russo, Emilio, Mecarelli, Oriano
Database ID:
RTHC-03215

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-ControlFollows or compares groups over time
This study
Cross-Sectional / Observational
Case Report / Animal Study

Enrolls participants and follows them forward in time.

What do these levels mean? →

Frequently Asked Questions

Did CBD work independently of clobazam?

Yes. The study found CBD effectiveness was independent of clobazam coadministration, though CBD was most commonly combined with valproic acid (62.2%) and clobazam (41.5%).

What were the main side effects?

The most common were somnolence (22.6%) and diarrhea (11.9%), followed by transaminase elevation and loss of appetite. Side effects led to dropout in 12.9% of patients.

Read More on RethinkTHC

Cite This Study

RTHC-03215·https://rethinkthc.com/research/RTHC-03215

APA

Iannone, Luigi Francesco; Arena, Gabriele; Battaglia, Domenica; Bisulli, Francesca; Bonanni, Paolo; Boni, Antonella; Canevini, Maria Paola; Cantalupo, Gaetano; Cesaroni, Elisabetta; Contin, Manuela; Coppola, Antonietta; Cordelli, Duccio Maria; Cricchiuti, Giovanni; De Giorgis, Valentina; De Leva, Maria Fulvia; De Rinaldis, Marta; d'Orsi, Giuseppe; Elia, Maurizio; Galimberti, Carlo Andrea; Morano, Alessandra; Granata, Tiziana; Guerrini, Renzo; Lodi, Monica A M; La Neve, Angela; Marchese, Francesca; Masnada, Silvia; Michelucci, Roberto; Nosadini, Margherita; Pilolli, Nicola; Pruna, Dario; Ragona, Francesca; Rosati, Anna; Santucci, Margherita; Spalice, Alberto; Pietrafusa, Nicola; Striano, Pasquale; Tartara, Elena; Tassi, Laura; Papa, Amanda; Zucca, Claudio; Russo, Emilio; Mecarelli, Oriano. (2021). Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome.. Frontiers in neurology, 12, 673135. https://doi.org/10.3389/fneur.2021.673135

MLA

Iannone, Luigi Francesco, et al. "Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome.." Frontiers in neurology, 2021. https://doi.org/10.3389/fneur.2021.673135

RethinkTHC

RethinkTHC Research Database. "Results From an Italian Expanded Access Program on Cannabidi..." RTHC-03215. Retrieved from https://rethinkthc.com/research/iannone-2021-results-from-an-italian

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.