Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review.
Naltrexone can take the edge off irritability in some autistic kids, but you still need ABA to build social and communication skills.
01Research in Context
What this study did
The team looked at 10 small drug trials. All tested naltrexone in autistic children.
They pooled the results to see if the pill calmed core autism signs or just tricky behaviors.
What they found
About 3 in 4 kids were less irritable and hyper. Core social and language signs stayed the same.
The drug helped side behaviors, not the main autism traits.
How this fits with other research
Huguenin (2000) once said no pill reliably eases autism aggression. Boudreau et al. (2015) updates that view. Their stricter review shows naltrexone does lower irritability, so the old claim is partly superseded.
Laposa et al. (2017) warn that parent ratings can improve even without treatment. Because most naltrexone trials used the same parent forms, some of the 77% gain could be placebo. The studies seem to clash, yet both can be true: naltrexone beats sugar pill, but part of the win is expectation.
Ramírez-Guerrero et al. (2025) found antioxidant pills give mixed, tiny gains. Like naltrexone, they rarely touch core social skills. The pattern across reviews is clear: pills may calm the body, but they don’t teach social interaction.
Why it matters
You can think of naltrexone as a helper, not a teacher. If a child is so hyper that learning stalls, a low dose might settle them for 2–3 hours. Use that calm window to run your social-skills program. Keep measuring with direct observation, not just parent forms, to be sure the gain is real.
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02At a glance
03Original abstract
BACKGROUND: ASC (autism spectrum conditions) may result from a failure of striatal beta endorphins to diminish with maturation. Many symptoms of ASC resemble behaviours induced in animals or humans by opiate administration, including decreased socialisation, diminished crying, repetitive stereotypies, insensitivity to pain and motor hyperactivity. Naltrexone, an opioid antagonist, has been used in the management of children with ASC and can produce a clinically significant reduction in the serious and life-threatening behaviour of self-injury for individuals who have not been responsive to any other type of treatment and is important for this reason. It was therefore appropriate to reconsider the available evidence and a systematic review was undertaken. METHODS: Four electronic databases were searched for relevant journal articles. In addition, cross-referencing of pertinent reviews and a hand search for articles in major international intellectual disability (ID) journals between the years 2010 and 2012 was carried out to ensure that all relevant articles were identified. We also searched databases for unpublished clinical trials to overcome publication bias. Each database was searched up to present (February 2013) with no restrictions on the date of publication. The search terms consisted of broad expressions used to describe ID and autistic spectrum disorder as well as terms relating to opioid antagonists and specific drugs. All studies identified by the electronic database search and hand search were examined on the basis of title alone for relevance and duplication. The abstracts of the remaining papers were then scrutinised against the inclusion criteria. Where abstracts failed to provide adequate information, the full texts for these papers were obtained. All the full texts were then evaluated against the inclusion proforma. Two reviewers carried out all the stages of the process independently. The reviewers met to discuss their selections and where disagreements arose, these were settled by discussion with a member of the study group. Data from each study meeting the inclusion criteria were extracted on a pre-piloted data extraction form. The quality of each study was further assessed using the Jadad scale, a tool developed to assess the quality of randomised controlled trials. RESULTS: 155 children participated in 10 studies; 27 received placebo. Of the 128 that received naltrexone 98 (77%) showed statistically significant improvement in symptoms of irritability and hyperactivity. Side effects were mild and the drug was generally well tolerated. CONCLUSIONS: Naltrexone may improve hyperactivity and restlessness in children with autism but there was not sufficient evidence that it had an impact on core features of autism in majority of the participants. It is likely that a subgroup of children with autism and abnormal endorphin levels may respond to naltrexone and identifying the characteristics of these children must become a priority.
Journal of intellectual disability research : JIDR, 2015 · doi:10.1111/jir.12122