Non-Psychoactive Cannabis Extract Disrupts Reinstatement and Reconsolidation in Cocaine-Induced Conditioned Place Preference in Mice

BACKGROUND: L., has shown promising preclinical effects in disrupting the consolidation and retrieval of drug-associated memories, thereby attenuating relapse-like behaviors. OBJECTIVES: The present study evaluated the effects of a low-THC CBD-rich cannabis extract (NPCE) on the reinstatement and reconsolidation of cocaine-induced conditioned place preference (CPP) in male CD1 (ICR) mice, an approach not previously investigated. METHODS: The extract was administered at a dose equivalent to 20 mg/kg of CBD. Treatment significantly attenuated both priming- and stress-induced reinstatement of cocaine-induced CPP. Reinstatement was triggered either by a cocaine priming injection or by acute stress exposure, whereas reconsolidation-like processes were assessed by administering the extract following memory reactivation sessions and subsequently evaluating the persistence of cocaine-associated preference over time. RESULTS: NPCE showed a consistent result with disruption of reconsolidation-like processes of cocaine-associated memory, with effects persisting for at least two weeks. The extract alone did not induce conditioned preference or aversion. CONCLUSIONS: These findings suggest that NPCE modulates drug-associated memory processes involved in relapse-like behavior. However, the underlying mechanisms were not directly evaluated and remain to be elucidated. Further studies are warranted to include both sexes, evaluate effects across multiple behavioral paradigms, directly compare full-spectrum extracts with isolated cannabinoids, and incorporate receptor-specific approaches to clarify the mechanisms of action.