Cannabidiol is a behavioral modulator in BTBR mouse model of idiopathic autism

Front Neurosci. 2024 May 9:18:1359810. doi: 10.3389/fnins.2024.1359810. eCollection 2024.

Abstract

Introduction: The prevalence of Autism Spectrum Disorder (ASD) has drastically risen over the last two decades and is currently estimated to affect 1 in 36 children in the U.S., according to the center for disease control (CDC). This heterogenous neurodevelopmental disorder is characterized by impaired social interactions, communication deficits, and repetitive behaviors plus restricted interest. Autistic individuals also commonly present with a myriad of comorbidities, such as attention deficit hyperactivity disorder, anxiety, and seizures. To date, a pharmacological intervention for the treatment of core autistic symptoms has not been identified. Cannabidiol (CBD), the major nonpsychoactive constituent of Cannabis sativa, is suggested to have multiple therapeutic applications, but its effect(s) on idiopathic autism is unknown. We hypothesized that CBD will effectively attenuate the autism-like behaviors and autism-associated comorbid behaviors in BTBR T+Itpr3tf/J (BTBR) mice, an established mouse model of idiopathic ASD.

Methods: Male BTBR mice were injected intraperitoneally with either vehicle, 20 mg/kg CBD or 50 mg/kg CBD daily for two weeks beginning at postnatal day 21 ± 3. On the final treatment day, a battery of behavioral assays were used to evaluate the effects of CBD on the BTBR mice, as compared to age-matched, vehicle-treated C57BL/6 J mice.

Results: High dose (50 mg/kg) CBD treatment attenuated the elevated repetitive self-grooming behavior and hyperlocomotion in BTBR mice. The social deficits exhibited by the control BTBR mice were rescued by the 20 mg/kg CBD treatment.

Discussion: Our data indicate that different doses for CBD are needed for treating specific ASD-like behaviors. Together, our results suggest that CBD may be an effective drug to ameliorate repetitive/restricted behaviors, social deficits, and autism-associated hyperactivity.

Keywords: autism spectrum disorders; behavioral assays; cannabidiol; repetitive behaviors; social deficits.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors graciously thank the following agency for the funding which supported in part of this work: SS (Autism Speaks Predoctoral Fellowship, T32ES011564), NM (R21HD110951), GB (P30ES030283-01A1, R01HG011598, NSF2213985) and Z-HS (R21EY030186).