In the late 2019, an epidemic of cases with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has spread from China to the rest of the world, resulting in a global pandemic (COronaVIrus Disease 19, COVID-19 pandemic). Starting from the first months of 2020, several restrictions have been imposed by governments to face the public health threat, impacting the usual patterns of drug abuse throughout the world (1). The temporary border closure affected the usual illicit drug route of shipping from country to country, resulting in scarcity of classic street drugs (2). Moreover, restrictive measures internationally adopted by several countries made necessary to close all the usual recreational settings in which stimulants drugs are commonly abused. On the contrary, since in house drugs abuse became the most feasible option, other private encounters might have caught on, such as chemsex (3). In particular this phenomenon, which originated mainly in the large cities of Northern Europe, has gradually spread across the continent and is now a worrying reality in western European countries. Other rising trends of substance abuse include cognitive enhancers and new psychoactive substances (4, 5). Furthermore, the consequent social isolation and the likely limited access to detoxification centers caused additional psychological distress, pushing drug addicts toward alternative psychotropic drugs, possibly through illegal online marketplaces. An international overview of the new trends of drug abuse during the current COVID-19 pandemic and the related health risks are hereby discussed, taking into consideration different points of view. Can New Trends of Substance Abuse Be Identified During COVID-19 Pandemic? As we write this opinion paper, the social and economic restrictions due to the coronavirus pandemic have already seriously impacted health and social fields. COVID-19 outbreak has led to the implementation of social distancing to contain the spread of the disease, changing people’s lifestyle. People have been going through a moment of anxiety and fear for their health and their jobs, and they are forced to live an unfamiliar lifestyle, deprived of relationships. Furthermore, the condition of people with psychological troubles may have worsened during the pandemic as a result of the unconsciously mirroring of others feelings (6). This peculiar situation may have pushed more people toward a deviant behavior linked to licit or illicit substance use, and it may have been a good opportunity for drug dealers to attract new customers. However, global issues have not favored the usual trade business. Indeed, social distancing has substantially reduced drug trafficking on the streets, pushing consumers toward illegal markets on the dark web or through messaging applications (7). Furthermore, the paucity of classic drugs, together with the impossibility to go out to look for those, might have induced addicts to misuse psychoactive prescription drugs such as benzodiazepines (8–10). In this concern, although there is limited scientific evidence, the impact of the COVID-19 pandemic could lead to substantial modifications in substance use patterns, and an increased risk of substitution, adulteration, contamination, and dilution with a potentially harmful substance. As such, reports from forensic science and toxicology laboratories are crucial for the early detection and response to such events (11, 12). Moreover, in this period of home confinement, users might no longer be looking for “socializing” substances to be used in recreational settings, but for psychotropic drugs to be consumed in solitude. Even short periods of isolation and loneliness can have negative consequences on physical and mental well-being. The feeling of isolation can lead to anxiety and anger, and even sleep disorders, depression, and post-traumatic stress disorders, which may be underestimated due to the lack of specific screening tools (13, 14). Moreover, psychiatric assistance from health professionals is not assured due to the temporary monopolization of psychiatric facilities for COVID-19 treatment (15). In addition to drug addicts using prescription sedatives available at home, some may have shifted to narcotics such as new synthetic opioids or designer benzodiazepines, available online. Indeed, these two classes of new psychoactive substances showed the highest consumption increase in 2019 (16–19).