Abstract
Abstract Background Catha edulis (khat) is a stimulant plant endemic to East Africa and the Arabian Peninsula, widely consumed for its psychostimulant effects, which are primarily attributed to cathinone and cathine. Despite an estimated 20 million daily users globally, the neurocognitive consequences of khat use, particularly on spatial learning and memory, remain incompletely characterized in preclinical models. Objectives This narrative review aimed to critically synthesize preclinical evidence regarding the effects of Catha edulis on spatial cognition and memory in rodents, with specific attention to dose-response relationships, exposure duration, and behavioral paradigm selection. Methods A structured literature search was conducted in PubMed, ResearchGate, Elsevier, EMBASE, and Web of Science (search end date: May 25, 2025) using predefined Medical Subject Headings (MeSH) terms and keyword combinations. Screening followed PRISMA 2020 methodology. Fourteen primary studies (n = 610 rodents) met all inclusion criteria. Study quality and risk of bias were assessed using the SYRCLE Risk of Bias tool. Results/Conclusions Fourteen studies meeting inclusion criteria were identified, comprising 610 rodents across several mouse and rat strains, predominantly Swiss albino mice, with additional CBA mice, C57BL/6 mice, adult albino mice, and Wistar rats. Acute exposure (single dose; 40–500 mg/kg) produced dose-dependent bidirectional effects on spatial task performance. Subacute exposure (≤ 28 days) was consistently associated with spatial learning deficits. Subchronic exposure (29–90 days) yielded the most robust impairment profiles across multiple behavioral paradigms. Chronic exposure (> 90 days) resulted in persistent spatial learning and memory deficits; however, reversibility remains unknown as no included study incorporated a washout period. Risk-of-bias assessment revealed high-performance bias in 78.6% of studies. Standardized preclinical protocols and prospective translational studies are urgently required to bridge the gap between rodent findings and human neurocognitive outcomes in khat users.