Potential use of propranolol in autism spectrum disorder: A narrative review

Abstract

Rationale:

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication difficulties and restricted, repetitive behaviors. Although several pharmacological agents have been trialed, treatments for core features remain limited. Propranolol, a non-selective β₁/β₂-adrenoceptor antagonist (β-blocker, NbN), has shown potential effects across multiple ASD-related domains.

Methods:

A narrative review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses principles. Systematic searches in PubMed, Scopus, ScienceDirect, and ProQuest identified 22 studies, of which 15 were included, comprising randomized controlled trials, single-dose psychopharmacological challenge studies, and reviews.

Results:

Evidence suggests that propranolol may improve social anxiety, verbal problem-solving, cognitive flexibility, emotional regulation, and behavioral dysregulation. Benefits of facial scanning and verbal fluency have also been described. The drug may attenuate adrenergic hyperarousal and promote parasympathetic dominance. However, most positive findings derive from small samples or single-dose studies, while sustained double-blind trials are scarce. Polypharmacy contexts remain underexplored.

Discussion:

Propranolol may serve as an adjunctive therapy in selected ASD cases, particularly when other strategies are insufficient. Its central nervous system penetration and anxiolytic profile support potential clinical use. Emerging evidence suggests that autonomic biomarkers and pharmacogenetic factors (e.g., CYP2D6, ADRB1/2 polymorphisms) could inform patient selection.

Conclusions:

Propranolol shows promise in modulating adrenergic activity relevant to several ASD symptom domains. The most consistent evidence supports anxiolytic effects under sustained dosing, whereas cognitive and behavioral findings remain preliminary. Larger, placebo-controlled trials with biomarker integration are needed to clarify efficacy, long-term safety, and clinical positioning. Until then, its use should remain cautious and highly individualized.