Interaction of Catha edulis (Vahl) Forssk. ex Endl. (Khat) and the Endocannabinoid System on Spatial Learning and Memory in Mice

Numerous studies have looked into the neurocognitive impact of cannabinoid ligands. The effect of Catha edulis (Vahl) Forssk. ex Endl. (khat) on learning and memory is also researched by few scholars, although the findings are inconsistent. Moreover, the interaction of cannabis with other drugs of abuse is well studied. According to recent reports, the endocannabinoid system modulates the neurobehavioural effects of khat, including motor activities, working memory, and anxiety-like behaviours. However, it is not known whether such modulation is apparent in spatial learning and memory. To this effect, mice were subjected to acute exposure to khat and cannabinoids (agonists and antagonists) and spatial learning and memory were assessed using a battery of tests including the radial arm maze, multiple T-maze and the Morris water maze. Parameters including latency, correct/incorrect decision, reference memory error, and working memory error were determined. The study revealed that acute khat exposure did not have a substantial effect on spatial learning and memory. Method-dependent pro-cognitive effect was observed with single administration of JWH-133 (CB2R agonist) and cannabidiol. By contrast, WIN-55,212-2 (a nonselective CBR agonist) resulted in significant impairment of cognition. Whereas, co-administration of khat with cannabinoid agonists attenuated the effect produced by the agonists regardless of the direction of change(enhanced or reduced cognition). Co-administration with inverse agonists/antagonists, however, had a procognitive effect. Especially, co-administration of khat and the cannabinoid 1 receptor inverse agonist/antagonist AM-251 improved spatial learning and memory. Overall, this research indicates that khat could potentially be able to modify how the endocannabinoid system affects spatial learning and memory.