Repeated high doses of MDMA impaired mice's ability to learn and recall an active avoidance task. Pretreatment with a low dose (5 mg/kg) of the endogenous PPAR-α agonist oleoylethanolamide (OEA) partially protected against these deficits, while a higher dose (25 mg/kg) worsened them. MDMA also reduced dopamine transporter (DAT)-binding sites in the brain four days after the last dose, an effect prevented by both OEA doses. Coexpression of tyrosine-hydroxylase and PPAR-α receptors was observed in the striatum and substantia nigra pars compacta, suggesting OEA modulates MDMA-induced cognitive deficits through a DAT-independent mechanism.
Cannabis use during adolescence and young adulthood is linked to memory problems, especially in episodic and working memory, but effects on executive functions are less consistent and depend on age, how much cannabis is used, and the type of cognitive test. Studies from the Americas, many of which followed participants over time, more often found negative associations between cannabis use and cognitive performance. European studies showed mixed results, possibly due to differences in cannabis products, patterns of co-use, and measurement methods. Evidence from Asia was limited. Overall, cognitive differences are more reliably seen in adolescents than in young adults, shaped by developmental, methodological, and contextual factors.