International forskning

Second-line cannabis therapy in patients with epilepsy

Erica Braun e, Francesca M. Gualano b, Prabha Siddarth c, Eric Segal a b d

  • 1Joseph M. Sanzari Children’s Hospital, Hackensack, NJ 07601, USA.
  • 2Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA. Electronic address:
  • 3Semel Institute for Neuroscience and Human Behavior, School of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA.
  • 4Hackensack University Medical Center, Hackensack, NJ 07601, USA; Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA; Northeast Regional Epilepsy Group, Hackensack, NJ 07601, USA


Objective: Marijuana-based therapies (MBTs) have been shown to reduce seizure frequency in patients with severe and drug-resistant epilepsy (DRE). Pharmaceutical-grade CBD (Epidiolex) was approved by the FDA in 2018 for the treatments of Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS) and subsequently in 2020 for tuberous sclerosis complex (TSC). It is unclear what the utility would be in prescribing one type of MBT if a previous, alternative type failed. We conducted a retrospective study to determine if an alternative formulation of MBT reduces seizure frequency if the patient has not had a meaningful response from an initial MBT. We also investigated the clinical impact that a second MBT has on side effect profile.

Methods: We reviewed the charts of patients with DRE who were at least 2 years old and who took at least 2 different formulations of MBT, including a pharmacologic formulation of CBD (Epidiolex), artisanal marijuana, and/or a hemp-based formulation. We reviewed medical records in patients 2 years of age and older; however, subjects’ historical data, such as age of first seizure onset, may be prior to the age of 2 years. We extracted data on demographics, type of epilepsy, history of epilepsy, medication history, seizure count, and drug side effects. Seizure frequency, side effect profiles, and predictors of responder status were evaluated.

Results: Thirty patients were identified as taking more than 1 type of MBT. Our findings suggest that seizure frequencies do not change significantly from baseline to after the first MBT and to after the second MBT (p = .4). However, we did find that patients with greater baseline seizure frequency were significantly more likely to respond to treatment after the second MBT (p = .03). To our second endpoint of side effect profile, we found that patients who experienced side effects after a second MBT had significantly greater seizure frequency compared to those who did not (p = .04).

Conclusion: We found no significant seizure frequency reduction from baseline to after a second MBT in patients who tried at least 2 different formulations of MBT. This suggests a low probability of seizure frequency reduction with a second MBT therapy in patients with epilepsy who tried at least two different MBTs. While these findings need to be replicated in a larger sample, they suggest that clinicians should not delay care by trying alternative MBT formulations after a patient has already tried one. Instead, it may be more prudent to attempt an alternative class of therapy.

Keywords: Cannabidiol; Drug-Resistant Epilepsy; Marijuana; Marijuana-Based Therapy; Medication-Refractory Epilepsy; Seizure.