The history of autism "cures" is a history of dashed hopes and frequent danger.
Our data suggest that leucovorin prescription rates rose sharply following the September 2025 announcement by White House leaders but began a steadier increase in February 2025, after being stable for 2 years. A recent analysis4 reported increased leucovorin prescriptions in children following the White House announcement. Our study extends these findings by examining a longer observation period and restricting the cohort to children with a prior ASD diagnosis, which reveals that the upward trend in prescribing began months before the announcement and was specific to the population of greatest clinical interest.
A February 17, 2025, CBS Evening News segment titled “Parents say off-label drug helped son with autism speak”6 described a family whose child was diagnosed with autism when aged 2.5 years and was prescribed off-label leucovorin when aged 3 years. According to his mother, he spoke his first word within days of starting the medication, and by age 5 years, he had enrolled in a mainstream kindergarten program. Following the CBS segment, the story received substantial media attention, and Autism Speaks, the largest autism nonprofit organization in the US, highlighted the news on their website on February 25, 2025.7
Our findings suggest that mainstream media information about leucovorin’s potential use in ASD and the 2025 announcement by White House leaders may be associated with substantial increases in leucovorin use in children with ASD. Although no large randomized clinical trials have been initiated to assess the safety and efficacy of leucovorin for ASD, an increasing number of patients are being prescribed the medication. Notably, on March 10, 2026, the FDA approved leucovorin for the treatment of cerebral folate transport deficiency due to confirmed FOLR1 gene variants.8 However, the FDA did not approve leucovorin for ASD. This regulatory decision warrants ongoing surveillance of leucovorin prescribing for children with ASD. This study has limitations, including reliance on prescription-level data without confirmation of medical indication, inability to assess patient-level clinical outcomes, and lack of adjustment for site-level variation in Epic Cosmos participation. The rapid increase in leucovorin use for ASD, the timing of which is associated with otherwise exogenous events, may offer a novel natural experiment to better understand the potential behavioral effects of leucovorin in ASD.
