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Brief Report: Intranasal Ketamine in Adolescents and Young Adults with Autism Spectrum Disorder—Initial Results of a Randomized, Controlled, Crossover, Pilot Study

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Abstract

Dysregulation of glutamate neurotransmission plays a critical role in autism spectrum disorder (ASD) pathophysiology and is a primary target for core deficit research treatment trials. The mechanism of action of ketamine has striking overlap with the theory of ASD as a disorder of synaptic communication and neuronal networks. This two-dose, double-blind, placebo controlled, cross-over pilot trial of intranasal (IN) ketamine targeting core social impairment included individuals with ASD (N = 21) between 14 and 29 years. Participants were randomized to received two doses of IN ketamine (30 and 50 mg) and two doses of matching placebo. No significant impact was noted on the Aberrant Behavior Checklist Social Withdraw subscale. The IN ketamine was well tolerated, with only transient mild adverse effects.

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Funding

Funding for this project was provided by Cures Within Reach and Roivant Sciences. The authors report no competing financial interests related to the work described. Dr. Wink has received funding from the National Institute of Metal Health-National Institute of Child Health and Human Development via a T32 fellowship, as well as research funding from Autism Speaks. Dr. Wink has consulted for Ovid Therapeutics. Dr. Horn, Dr. Reisinger, Dr. Shaffer, Ms. O’Brien, and Dr. Schmitt have no conflicts to disclose. Dr. Dominick has received research support from the National Institute of Neurological Disorders and Stroke (NINDS), American Academy of Child and Adolescent Psychiatry, and Cincinnati Children's Hospital Medical Center. She is a clinical trial site investigator for F. Hoffman-La Roche Ltd. and Ovid Therapeutics. Dr. Pedapati has received research support from the National Institute of Health, American Academy of Child and Adolescent Psychiatry, and Cincinnati Children's Hospital Research Foundation. He is a clinical trial site investigator for the Marcus Autism Center for an investigational medical device. He receives compensation for consulting for Proctor & Gamble, Eccrine Systems, and Autism Speaks. He receives book royalties from Springer. Dr. Erickson receives current consulting revenue from Lenire Bioscience, Stalicla, and Confluence Pharmaceuticals. Dr. Erickson receives current research support from the National Institutes of Health, the United States Centers for Disease Control, the FRAXA foundation, Autism Speaks, the State of Ohio, and from the Cincinnati Children’s Hospital Research Foundation. Drs. Wink and Erickson are inventors on a patent describing use of ketamine in autism.

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Authors and Affiliations

  1. Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave. MLC 4002, Cincinnati, OH, 45229, USA

    Logan K. Wink, Debra L. Reisinger, Paul Horn, Rebecca C. Shaffer, Kaela O’Brien, Lauren Schmitt, Kelli R. Dominick, Ernest V. Pedapati & Craig A. Erickson

  2. University of Cincinnati College of Medicine, 3230 Eden Ave., Cincinnati, OH, USA

    Logan K. Wink, Paul Horn, Rebecca C. Shaffer, Lauren Schmitt, Kelli R. Dominick, Ernest V. Pedapati & Craig A. Erickson

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  1. Logan K. Wink
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Contributions

LW conceptualized experiments and wrote the primary draft of the manuscript. DR participated in data analysis, results interpretation, and in the writing of the manuscript. PH is the primary biostatistician on this project. RS, LS, KR, KO, and EP all participated in data collection and contributed to data analysis, results interpretation, and edited and reviewed the manuscript. CE participated in conceptualizing the experiments and contributed to the writing of the manuscript.

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Correspondence to Craig A. Erickson.

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Wink, L.K., Reisinger, D.L., Horn, P. et al. Brief Report: Intranasal Ketamine in Adolescents and Young Adults with Autism Spectrum Disorder—Initial Results of a Randomized, Controlled, Crossover, Pilot Study. J Autism Dev Disord 51, 1392–1399 (2021). https://doi.org/10.1007/s10803-020-04542-z

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