Scopolamine is a muscarinic receptor antagonist and is widely utilized as a “memory-loss model.” However, its impact across different memory and attention tasks and using different modes of administration has yet to be clearly evaluated. This systematic review and meta-analysis investigates the effect of scopolamine, across all routes of administration and across different dosages, on memory and attention performance in healthy humans (PROSPERO ID: CRD42024531634).

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched (on 20 April 2024) for studies that utilized scopolamine and assessed memory and/or attention. Random-effects meta-analyses were conducted across a range of memory and attention tasks using “Comprehensive Meta-Analysis,” Version 3, to evaluate differential pharmacological effects on cognitive tasks between the scopolamine and placebo groups.

Forty-six studies fulfilled the inclusion and exclusion criteria. Scopolamine negatively impaired performance on all memory tasks (immediate memory, delayed recall, digit span, Buschke selective reminding task, and recognition memory) and led to slower reaction times for three of the five attention tasks examined (choice reaction time, simple reaction time, and rapid visual information processing) compared to placebo. Scopolamine’s negative effect on memory and attention was greater with injectable (e.g., intramuscular, intravenous, and subcutaneous) compared to non-injectable routes of administration (e.g., intranasal, oral, and transdermal).

This study supports the use of scopolamine as a “memory-loss model,” particularly when given by an injectable route of administration. Future clinical trials should evaluate the bioavailability of scopolamine across different routes of administration to ensure therapeutic benefits outweigh any potential adverse cognitive effects.