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Leucovorin for kids with autism

More research is needed, but the results of small studies are promising
Wendy Wisner
By | Dec. 16, 2025 Medically reviewed by Leslie Greenberg, MD
A prescription bottle spilled over: Leucovorin for kids with autism

Key takeaways

  • While the FDA has stated that it will soon be approving leucovorin for autism, it has not yet been approved.

  • Research has found some promising uses for leucovorin in autism, but the research so far is limited and focuses mostly on autistic children with cerebral folate deficiency or children who have tested positive for folate receptor autoantibodies.

  • If you are interested in leucovorin for your child, you should connect with your child’s healthcare provider, who may be able to prescribe it off-label for your child.

In this article:

Leucovorin is a type of medication called a folic acid analog. It works by increasing folate levels (vitamin B9) in the body and protecting cells from the side effects of certain drugs. Leucovorin is currently approved by the Food and Drug Administration (FDA) to manage the side effects of large doses or overdoses of medications like methotrexate. Although managing drug side effects is leucovorin’s FDA-approved indication, it is also used off-label for several conditions, including cancer treatments and ectopic pregnancy treatments. In September 2025, the FDA announced that it would soon be approving Leucovorin for kids with autism. Leucovorin has already been used off-label for autism, and this move by the FDA could make the medication a more standard treatment option for autism in kids.

Leucovorin as a treatment for autism in kids

Autism, also known as autism spectrum disorder, is a neurodevelopmental disorder impacting the way people view the world, communicate and socialize with others, and behave. Symptoms are usually first noticed in early childhood, and it’s estimated to impact 1 in every 31 children.

There is a range of autism functionality, with some people needing very little support, some needing daily care, and some being non-verbal. Many people view autism not as a disease that’s meant to be cured, but as a different way of being.

What the research says

As the FDA mentioned in its September press release, there is some research showing positive use of leucovorin in people with cerebral folate deficiency (CFD), which is a condition that impacts the transport of folate to the brain. The FDA notes that people with cerebral folate deficiency share symptoms with people who have autism.

Other studies have looked specifically at the use of leucovorin supplementation for the treatment of some symptoms of autism. A 2020 review published in Seminars in Pediatric Neurology concluded that leucovorin may be able to “substantially improve” autism symptoms, including language and verbal communication skills, especially in those who test positive for folate receptor alpha autoantibodies.

While these studies show promise, experts note that it may be too soon to recommend leucovorin as a universal autism treatment for kids. Instead, what the research shows is that leucovorin may be a helpful potential treatment for certain autistic children. “It’s not a cure for autism, but it may help a specific group of children whose brains aren’t getting enough folate on their own,” says Nona Kocher, MD, a board-certified psychiatrist based in Miami.

“The strengths of these studies are that they are revealing a specific biological/mechanistic link between folinic acid therapy and ASD-symptom improvements for those individuals who have a genetic or other biological deficiency that leads to reduced folate availability in the brain,” says Jared Schwartzer, Ph.D., professor of psychology, neuroscience, behavior, and education at Mount Holyoke College.

On the other hand, the limitations of these studies are a relatively low sample size and a limited number of experiments. “This makes it difficult to generalize to a larger population or identify potential contraindications (populations for which this treatment could be harmful and should be avoided),” Dr. Schwartzer says.

Also, Dr. Kocher points out that even if leucovorin proves helpful for certain children, it is not a behavioral medication. “It’s targeting a specific metabolic pathway,” she explains. “That makes it very different from the usual tools we rely on, like stimulants or antipsychotics.”

Dr. Schwartzer notes that in these studies, leucovorin hasn’t shown significant adverse effects on kids. But that doesn’t mean it’s necessarily time to recommend it as an autism treatment. “The concern is not that Leucovorin is a dangerous or harmful medication,” he explains. “The concern is that there are claims being made about its effectiveness beyond what the data are presently able to support.”

On Oct. 31, 2025, the Academy of American Pediatrics (AAP) issued guidance about leucovorin and children. It states that it currently doesn’t recommend the routine use of leucovorin for autism in kids. The AAP acknowledges that small studies have found benefits for selected cases, but that more research is needed for a wider recommendation to be made. 

Leucovorin dosage for kids with autism 

As the AAP notes in its recent guidance, questions about a leucovorin dose for kids with autism still remain unanswered due to a lack of robust clinical trials. The FDA also has not yet released dosing guidance about leucovorin for autism in kids.

Dr. Schwartzer predicts that the dosing used in research reports will likely be incorporated in the FDA decision. “But I also want to express caution about using research doses as a means to self-medicate,” Dr. Schwartzer emphasizes. “Just because these doses are published in the literature does not mean they alone represent the safe and effective dose.”

 The typical dose mentioned in research ranges from “2 mg/kg per day, or 25 mg twice a day (50 mg maximum), and higher doses have been used for clinical evaluation purposes at a concentration of 50 mg twice a day,” Dr. Schwartzer says.

Leucovorin side effects and warnings

Like any medication, leucovorin can cause side effects. According to Dr. Kocher, the side effects most often seen in kids are restlessness, irritability, trouble sleeping, stomach upset, or headaches. But these are typically mild and can usually be managed by adjusting the dose.

“The studies that have looked at leucovorin and folinic acid supplementation for ASD symptoms report that the medication is well tolerated with few adverse effects,” Dr. Schwartzer says. “This is certainly encouraging. However, there have not been enough large-scale trials (for example, a Phase III clinical trial) that can scale the medication use up across a large enough population to identify any other potential side effects or contraindications.”

Who should not take leucovorin for autism?

Although leucovorin is largely safe, there are some people who should avoid it. Here are tips from Dr. Kocher:

  • Leucovorin can interfere with some chemotherapy drugs, so people with certain cancers should avoid it.
  • People on seizure medications should take precautions, since it may change how these medicines work and allow seizures to occur.
  • Anyone with a folinic acid allergy should avoid it.

According to the drug’s label, it’s not known whether leucovorin is safe for pregnant people, because no studies have been done on its safety in this population or the risk of birth defects if the medication is taken during pregnancy. It’s also not known whether leucovorin is excreted into breast milk. For these reasons, it’s best if pregnant or nursing parents discuss leucovorin with their healthcare provider before taking it.

How much does leucovorin cost? 

Without insurance, leucovorin costs about $36 for 12, 5 mg tablets, although prices vary by pharmacy, location, and dosage. With a SingleCare coupon, you can get leucovorin for even less, at $9 for 12, 5 mg tablets. SingleCare discount cards are free to use, and there are no hidden fees or premiums.

Will insurance cover leucovorin for autism?

Since the FDA has not yet approved leucovorin to treat autism, it’s unlikely that your health insurance company will cover the medication for this diagnosis. However, coverage varies by state and by policy. At times, if your healthcare provider requests prior authorization or proves that a medication is medically necessary, your insurance company may approve coverage.

How to get a leucovorin prescription for autism 

You can get a leucovorin prescription for autism for your child from your pediatrician or from another provider who specializes in autism, like a psychiatrist or neurologist. “When it’s given to children on the spectrum, it falls under what’s called ‘off-label’ use, which is something doctors do often when research suggests a benefit,” Dr. Kocher says. “It should only be started and monitored by a physician who knows this area, so the child is watched closely for both improvements and any side effects.”

Dr. Kocher emphasizes that even if your child is prescribed leucovorin, it should not be used as a standalone treatment, and it’s not the answer for every child with autism. “It may be useful for some children, but it works best as part of a broader plan that includes therapies, school supports, and other care tailored to your child’s needs,” she says.

The SingleCare prices in this article are the most accurate at the time of publishing in ZIP code 23666 as of Dec. 9, 2025. Prices vary by pharmacy. Visit our leucovorin coupon page for updated leucovorin prices near you.

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