Despite limited data, parents are rushing to find leucovorin for autism.

CHICAGO >> President Donald Trump’s adoption of an older generic drug called leucovorin for use in a rare disorder that causes autism-like symptoms has led to a surge in demand from parents who believe it can revitalize language skills and social connections in autistic children.

That poses a challenge to pediatricians and experts, who warn that the science on leucovorin in autism is limited and does not support widespread use.

A month after Food and Drug Administration (FDA) Commissioner Marty Makary touted that GSK’s decades-old drug could help “hundreds of thousands” of children with autism, doctors and researchers say they have been inundated with parents seeking information.

“My Facebook feed is flooded with parents swearing that leucovorin works,” said Dr. David Mandell, a psychiatry and autism researcher at the University of Pennsylvania.

Tens of thousands of people have joined a Facebook group called Leucovorin for Autism, which was started in May by Keith Joyce, the legal guardian of 4-year-old Jose, who takes the medication.

Joyce credits leucovorin for Jose’s improvements in verbal communication and social awareness. The site had 5,000 members on the day of Trump and McCurry’s White House announcement and now has 84,000.

Mandell and other scientists and doctors said the FDA’s approval, which does not require large, randomized clinical trials, leaves practitioners lacking the data, guidance or confidence to prescribe the drugs responsibly while facing emotional appeals from families.

Leucovorin is approved to treat chemotherapy side effects, but may be prescribed off-label for symptoms of autism.

“This puts doctors in a very difficult position because they are being asked to prescribe something that is not based on evidence,” said Dr. Shafali Jeste, an autism expert and UCLA pediatrician who does not prescribe leucovorin despite repeated requests.

The American Academy of Pediatrics said today that leucovorin is not recommended for routine use in children with autism.

The U.S. Centers for Disease Control and Prevention (CDC) reported in April that the prevalence of autism had risen to 1 in 31 children aged 8 years. Finding the root cause of the disease and potential treatments is something both Health Secretary Robert F. Kennedy Jr. and Trump advocate.

Despite the FDA commissioner’s broad comments, his agency proposed a narrower approval related to cerebral folate deficiency (CFD), a genetic disorder that can cause symptoms similar to autism. It affects approximately 1 in 1 million children worldwide.

The argument for wider use is based on small studies suggesting that many children with autism have autoantibodies that block folic acid, a vitamin important in brain signaling, from entering the brain, causing a deficiency similar to CFD.

It is estimated that about 75% of children with autism have these autoantibodies, but their significance has not been proven, said Dr. Karam Radwan, director of the Neurodevelopmental Disorders Program at the University of Chicago.

A HHS spokesperson said the FDA planned to update the leucovorin label to include CFD based on an analysis of more than 40 case studies published from 2009 to 2024. Overall, 85% of patients experienced some benefit, including improved language/communication skills.

HHS acknowledged that leucovorin may be useful in children with autoantibodies to folic acid, but that “data are limited and replication is needed.”

A spokesperson said the National Institutes of Health will support follow-up research into the effects of leucovorin on CFD and its potential benefits for individuals with autism. Post-marketing surveillance and safety studies are part of the plan.

Parents interpreted the FDA announcement as a green light for the use of leucovorin for autism and shared treatment tips that led Facebook to take down Joyce’s site. That was reinstated as a rule banning medication discussion, but was removed again last week for other violations.

Joyce began researching the drug after seeing a news program about the treatment of an autistic boy who showed significant speech improvements.

He found three studies, all written by the same author, to be credible. There have been no large trials comparing leucovorin to placebo in children with autism.

Joyce reviewed the drug’s performance in cancer patients, where leucovorin was associated with insomnia, agitation and depression. Doctors and parents say in children, it can cause hyperactivity, aggression and feelings of overwhelm.

Jose’s neurologist was reluctant to prescribe leucovorin, but the boy’s behavioral pediatrician, who had heard about the drug at a conference, was willing to do so.

The child’s care team measured language skills before and four months after treatment, Joyce said.

He is more aware of the world around him and more responsive, Joyce said. “It didn’t cure his autism, but it improved his quality of life. I’m sure it’s real.”

Radwan, who offers the drug in his practice, said doctors don’t fully understand who would benefit, how much they would benefit and whether it is sustainable. So far, the benefits have been “very minimal,” he said.

In some online communities, parents are urging caution.

Sophia Urwin, 33, a single parent from Wellington, New Zealand, is concerned that desperate parents are turning to over-the-counter folinic acid after her non-speaking four-year-old son was diagnosed with autism in 2022.

“When you’ve been skating on thin ice for so long, it’s really easy to get caught up in thinking something is a miracle ‘cure,’” she said.