Background: The protocols for mitigating the transmission of Covid-19 seem to be a trigger for the use of psychoactive substances, as an individual's adaptive response to support this new way of being in the world. Objective: To investigate the use of psychoactive substances in the context of the Covid-19 pandemic in Brazil. Method: A cross-sectional and prospective observational study, undertaken in a virtual environment. An online survey was developed and employed through Google Forms to collect data. The survey was made available to participants on social networks, Facebook@, Whatsapp@, and Instagram@, linked to the research group, during the period 06/15/2020 to 07/15/2020. 1,145 individuals participated in the research. Results: The average age of the participants was 37 years old. They were mostly female, white, Brazilians, with a higher education level, with occupations in the health field, and had religion. They either maintained their family income or suffered a small income decrease. Moreover, they informed that they were caring for social isolation. The most used substances before and after the beginning of the Covid-19 pandemic were alcohol, tobacco, marijuana, although the use of these substances decreased (P<0.001). Approximately 32% of the participants started using psychoactive substances in this period. Among them, most individuals started by their own initiative. Conclusions: For a better understanding of the pattern use of psychoactive substances during the Covid-19 pandemic and the adverse effects on human behavior and mental disorders, careful longitudinal studies must be developed, due to the great interest in the knowledge of adaptive responses when people's lives are at risk.