Inflammatory and epigenetic alterations associated with attention deficits in adolescents with cocaine base paste addiction

Cocaine base paste (CBP) is an intermediate product in the process of obtaining cocaine (COC), known for its low cost, high toxicity, and poor quality. Its use became widespread in Argentina during the socioeconomic crisis of 2001-2002 and is more prevalent among individuals under 25 and those from low socioeconomic backgrounds. This pilot study aimed to characterize inflammatory and epigenetic mechanisms involved in CBP and COC addiction, and their relationship to attention deficits. We analyzed adolescents with CBP dependence (n = 25), COC dependence (n = 22), and non-dependent controls (CTR, n = 25). Gene expression analysis revealed decreased levels of NF-κB and TNF-α in both drug-dependent groups. The CBP group also showed reduced expression of DNMT1 and DNMT3A, while only DNMT1 was decreased in the COC group. These changes were consistent with lower global DNA methylation levels in both groups compared to controls. We observed that DNMT1 expression was related to top-down attention. While higher DNMT1 levels were associated with better attention performance in the CTR and COC groups, the CBP group showed the opposite pattern. These findings support the presence of distinct molecular adaptations in CBP and COC abusers and may help identify potential targets linked to cognitive deficits in addiction.