Efeitos centrais do crack: uma abordagem experimental e epidemiológica

Abstract

The present study aimed to integrate preclinical and clinical evidence on the effects of crack cocaine by evaluating, in an animal model, its impact on conditioned place preference (CPP), depression-like behavior, and oxidative stress markers, as well as by synthesizing, through a systematic review, the prevalence of anxiety and depression among users of the substance. In the experimental component, male Swiss mice were exposed to crack cocaine smoke (0, 100, 200, or 400 mg) under two distinct CPP protocols (Protocol 1: one exposure per day for 5 consecutive days; Protocol 2: two exposures per day for 5 consecutive days). In Protocol 1, the 200 mg dose produced a significant increase in preference scores, indicating a reinforcing effect, whereas the other doses did not alter preference, suggesting an inverted U-shaped dose–response pattern. In Protocol 2, no significant CPP was observed, possibly due to behavioral extinction. In the forced swim test, all crack cocaine doses increased immobility time, indicative of depression-like behavior 24 hours after drug withdrawal. Biochemically, catalase activity in the hippocampus was elevated and sulfhydryl group content reduced, consistent with a redox imbalance, while plasma lactate dehydrogenase levels showed no significant change. The systematic review (26 studies; 9,428 participants) yielded pooled prevalence estimates of 30.4% for anxiety and 31.9% for depression, with medians of 26.8% and 43.4%, respectively, a predominance of male participants, and substantial methodological heterogeneity. Collectively, these findings demonstrate that crack cocaine induces marked neurobiological and behavioral alterations, and that its dependence is strongly associated with anxiety and depressive disorders. Further translational research is warranted to link oxidative stress biomarkers with behavioral and clinical parameters, thereby informing the development of integrated and personalized therapeutic interventions for this population.