The use of cannabis-based products for refractory epilepsy is associated with high perceived efficacy in a real-world public health setting in Brazil, with most patients reporting having their seizure frequency halved while experiencing mild-to-moderate adverse events (AEs).
In a cross-sectional study involving 91 patients (mean age 19.5 years, 58.2 percent male, 58.2 percent Black or Brown) with refractory epilepsy, 70.3 percent reported a ≥50-percent reduction in seizure frequency following the use of cannabis-based products. This perceived effectiveness was more frequently reported by current users than former users (94.7 percent vs 57.1 percent). [Clin Ther 2026;48:847-853]
More than half of the patients (51.6 percent) reported AEs, including sleep disturbances (28.6 percent), mood, psychiatric, or neurological changes (24.2 percent), and gastrointestinal symptoms (19.8 percent). Furthermore, 4.4 percent of patients reported an increase in seizure frequency, and 19.7 percent cited AEs as one of the reasons for discontinuing treatment.
In the multivariate analysis, at least 12 months of use of cannabis-based products was associated with greater odds of reporting a ≥50-percent reduction in seizure frequency (odds ratio, 23.79; p=0.013). Conversely, discontinuation of cannabis-based products due to access difficulties was associated with reduced odds of reporting a ≥50-percent reduction in seizure frequency (odds ratio, 0.074; p=0.003).
“The findings of the present study are consistent with the international real-world literature on the use of cannabis-based products for refractory epilepsies, which demonstrates clinically relevant reductions in seizure frequency in a significant proportion of patients despite important heterogeneity related to formulations, clinical characteristics, and regulatory contexts,” said first author Mariana Dias Lula from the Federal University of Minas Gerais in Belo Horizonte, Brazil, and colleagues. [Seizure 2023;109:11-18; Pediatr Neurol 2022;129:1-6; Brain Behav 2025;15:e70034]
The study did not investigate the exact ways in which cannabis might reduce seizure frequency, but previous studies have shown that cannabinoids can modulate brain activity and exert neuroprotective and anti-inflammatory effects that contribute to seizure control. [Front Neural Circuits 2022;15:781113; Physiol Rev 2024;104:591-649]
Product diversity
Lula and colleagues cautioned that not all cannabis-based products are created equal, saying that product quality, composition variability, and formulation type all influence seizure-control outcomes.
“Standardized pharmaceutical-grade products tend to provide greater therapeutic predictability, improved dose control, and more consistent chemical composition, aspects that are particularly relevant for clinical monitoring in refractory epilepsies,” the authors said.
Nevertheless, they noted that artisanal and nonregulated products still represent an important access route for patients in low- and middle-income countries despite important limitations related to variability in composition, safety, and product quality.
“Taken together, our findings contribute to the growing body of real-world evidence regarding medicinal cannabis use in refractory epilepsy and reinforce the need for prospective studies, formulation standardization, active pharmacovigilance, and public policies capable of ensuring continuous, safe, and regulated access to treatment,” Lula and colleagues said.
Refractory epilepsy population
The cross-sectional study was conducted in the Federal District, a federative unit that includes Brazil’s capital city and has approximately 3 million inhabitants. Most of the patients were 0–18 years of age (64.8 percent).
Of the patients, 40.7 percent had idiopathic focal epilepsy, and 23.1 percent had symptomatic focal epilepsy with complex seizures. Most patients (71.4 percent) presented coexisting conditions, including autism spectrum disorder (23.1 percent), paralysis (12.1 percent), and cognitive impairment (11 percent).
All patients had previously received antiepileptic drugs (AEDs), with a mean of 3.9 medications. Additionally, 14.3 percent had undergone surgical procedures for seizure control, 41.8 percent had adopted a ketogenic diet at some point, and 59.3 percent had undergone genetic testing. Isolated cannabidiol was the most used formulation (73.6 percent) of cannabis-based products.
Open conversations
In a linked commentary, Christine Baily of C Baily Law LLC in Arlington, Massachusetts, US, pointed out that healthcare professionals in the US are well positioned to talk to patients about medical marijuana. [Clin Ther 2026;48:883-886]
“Federal and state laws and regulations prevent patients from learning about the benefits and risks of marijuana, and its known medical and therapeutic uses. These restrictions, however, should not prevent healthcare providers from being a resource to patients,” Baily noted.
“Providers may not realize that the Controlled Substances Act (CSA), the federal law classifying marijuana, does not prohibit them from discussing and even recommending marijuana with their patients,” she added.
Baily explained that while the CSA prohibits healthcare providers from prescribing or ordering marijuana, federal law does not restrict healthcare providers from discussing and even recommending marijuana to their patients, regardless of whether it is classified under either Schedule I (adult marijuana) or Schedule III (state legalized medical marijuana and FDA-approved cannabis products) controlled substance.
“Given the rapidly evolving nature of federal and state laws and regulations, providers are encouraged to consult legal and other advisors to develop policies and procedures that enable them to address the needs of patients who may benefit from marijuana use,” she said.