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Intranasal Oxytocin Doesn’t Boost Social Functioning

Oxytocin is ineffective at improving social abilities in children with autism.

Key points

  • For this Phase 2 trial, 277 people (ages 3-17) with ASD were administered oxytocin or placebo via nasal spray for 24 weeks.
  • In smaller, less robust studies, oxytocin showed promise as a treatment. This placebo-controlled trial found it's safe but ineffective.
  • Intranasal oxytocin shows no evidence of helping children with autism spectrum disorder (ASD) improve social function.
Source: Picsfive/Shutterstock

Despite its reputation for being a "love hormone" or "cuddle molecule," growing evidence suggests that oxytocin doesn't always promote social bonding, positive emotions, or magnanimous human behavior.

For example, earlier this year, a study (Wong et al., 2021) by researchers at Concordia University reported that administering intranasal oxytocin can enhance the vividness of negative memories and may increase depression risk when given to people in non-social contexts where they feel isolated or unsupported.

This week, the long-awaited results of a randomized, double-blind, placebo-controlled clinical trial revealed that intranasal oxytocin does not improve social behaviors in children and adolescents with autism spectrum disorders. These peer-reviewed findings (Sikich et al., 2021) were published on October 14 in the New England Journal of Medicine.

Smaller, Less Robust Studies Gave Us False Hope in Oxytocin's Benefits

For those who had high hopes that intranasal oxytocin would prove to be an effective ASD therapy, the final results of this phase 2 clinical trial (NCT01944046) are disappointing.

"There was a great deal of hope this drug would be effective," the study's principal investigator and lead author, Linmarie Sikich of Duke University School of Medicine's Department of Psychiatry and Behavioral Sciences, said in a news release. "All of us on the study team were hugely disappointed, but oxytocin does not appear to change the social function of people with autism."

Previous research into oxytocin's ability to improve social functioning in those with autism during childhood and adolescence has shown conflicting results; some studies showed benefits, others did not. However, earlier experimental studies and small clinical trials were not as large or robust as Sikich et al.'s recent (2021) Phase 2 clinical trial.

For this nationwide study, researchers from numerous institutions across the United States conducted a 24-week, placebo-controlled Phase 2 trial of intranasal oxytocin therapy in 277 children and adolescents (ages 3 to 17) who'd been diagnosed with ASD. A total of 139 participants were assigned to the oxytocin group and 138 to the placebo group.

Oxytocin or placebo was administered intranasally, with a total target dose of 48 international units daily. The primary outcome was based on the least-squares mean change from baseline on the 13-item Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW). Secondary outcomes involved two additional measures of social function and a brief IQ test. The authors sum up their findings:

"This placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks."

Intranasal Oxytocin May Be Safe, but It's Ineffective

"Thousands of children with ASD were prescribed intranasal oxytocin before it was adequately tested. Thankfully, our data show that it is safe," senior author Jeremy Veenstra-VanderWeele of Columbia University and the New York State Psychiatric Institute noted.

"Unfortunately, [intranasal oxytocin] is no better than placebo when used daily for months. These results indicate that clinicians and families should insist that there is strong evidence for the safety and benefit of new treatments before they are provided to patients in the clinic," he added.

In closing, Sikich speculates that the negative findings of this study may preclude further research into intranasal oxytocin as a viable autism treatment. "Our consensus as investigators is that there is no evidence in this large study that is strong enough to justify more investigation of oxytocin as a treatment for autism spectrum disorders," she concluded.


Linmarie Sikich, Alexander Kolevzon, Bryan H. King, Christopher J. McDougle, Kevin B. Sanders, Soo-Jeong Kim, Marina Spanos, Tara Chandrasekhar, Pilar Trelles, Carol M. Rockhill, Michelle L. Palumbo, Allyson Witters Cundiff, Alicia Montgomery, Paige Siper, Mendy Minjarez, Lisa A. Nowinski, Sarah Marler, Lauren C. Shuffrey, Cheryl Alderman, Jordana Weissman, Brooke Zappone, Jennifer E. Mullett, Hope Crosson, Natalie Hong, Stephen K. Siecinski, Stephanie N. Giamberardino, Sheng Luo, Lilin She, Manjushri Bhapkar, Russell Dean, Abby Scheer, Jacqueline L. Johnson, Simon G. Gregory, and Jeremy Veenstra-VanderWeele. "Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder." New England Journal of Medicine (First published: October 14, 2021) DOI: 10.1056/NEJMoa2103583

Shiu F. Wong, Christopher Cardoso, Mark A. Orlando, Christopher A. Brown, Mark A. Ellenbogen. "Depressive Symptoms and Social Context Modulate Oxytocin’s Effect on Negative Memory Recall." Social Cognitive and Affective Neuroscience (First published: June 18, 2021) DOI: 10.1093/scan/nsab072