Since ancient times, the use of substances such as cacao, cannabis and peyote was part of cultural and religious practices, without being considered a social problem. However, in the 19th century, the use of substances such as opium and cocaine intensified, generating concern, especially among the upper classes and urban workers. In the early twentieth century, this consumption began to be associated with racial degeneration and decadence, especially after the expansion of European colonialism. In Mexico, the criminalization and prohibition of marijuana and alcohol in the 1920s was linked to the lower classes and immigrants, reflecting the social concerns of the time. Since the 21st century, anti-drug policies, especially during the Calderon, Peña Nieto, Obrador and Sheinbaum governments, have increased violence and public health problems. The prohibitionist model has failed to control consumption and Substance Use Stigma (SUS) has contributed to the marginalization of users, limiting their access to treatment and perpetuating their social exclusion in areas such as employment, education and health, among others. This research focuses on the coping strategies of SUS using semi-structured interviews with users in the Bajio region. The results show that the main coping strategy is concealment, which reflects a desire to protect privacy. Proactive strategies also emerge, such as denial, that allow stigma to be challenged through concrete evidence, in a geographical context marked by conservatism, due to the deep relationship between culture, religion and the predominant social norms in the communities of the region. Added to this is the presence of a paralegal biopower, characterized by the influence of organized crime groups. The potential to reconfigure the narrative around the illegalized substance use is highlighted, highlighting the resilience of users. Coping strategies emerge as valuable tools to counter stigmatization and encourage a human rights-centered approach.