Differential effects of cannabidiol on inhibitory avoidance memory reconsolidation and consolidation are associated with distinct hippocampal proBDNF and BDNF signaling profiles.

Dai W.; Huang W.; Hu S. · Frontiers in neuroscience · 2026

**Background & Methods** This review examined cannabidiol's (CBD) effects on inhibitory avoidance (IA) memory reconsolidation and consolidation in mice. The study involved administering CBD at varying doses during different memory phases, with co-administration of the Trk receptor antagonist K252a to evaluate tropomyosin receptor kinase signaling involvement, and anisomycin (ANI) to induce memory consolidation impairments. Hippocampal proBDNF and mature BDNF levels were measured to elucidate underlying molecular mechanisms. **Key Findings** • CBD impaired IA memory reconsolidation in a dose-dependent manner through Trk signaling-dependent reduction of hippocampal proBDNF levels, without altering mature BDNF expression; this effect was completely abolished by K252a co-administration. • CBD did not affect IA memory consolidation under baseline conditions but demonstrated protective effects against ANI-induced memory consolidation deficits by restoring hippocampal mature BDNF levels; this neuroprotective effect was blocked by K252a, indicating Trk signaling dependence. • CBD exhibited bidirectional, context-dependent effects on memory processes mediated by distinct neurotrophic mechanisms: proBDNF reduction during reconsolidation versus mature BDNF restoration during consolidation recovery. **Dosage & Administration** Specific doses and routes of CBD administration were not detailed in the abstract; doses were described as "different doses" administered during reconsolidation or consolidation phases in mice models. **Safety & Adverse Effects** The abstract notes that CBD possesses "low toxicity and minimal euphoric effects" and describes antipsychotic, anxiolytic, and neuroprotective properties. No specific adverse effects from the experimental interventions were reported. **Evidence Quality** As a review article published in 2026, this work synthesizes existing literature rather than presenting original experimental data. Key limitations include: reliance on animal models (mice) with uncertain translational applicability to humans; incomplete reporting of methodological details in the abstract; and potential publication bias in reviewed literature. The findings provide mechanistic insights but require validation through clinical trials before application to memory-related disorders in human populations. The distinction between reconsolidation and consolidation effects represents a notable methodological strength in differentiating CBD's context-dependent mechanisms.

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