Lockdown measures in response to the COVID-19 pandemic in 2020 yielded dramatic changes in drug consumption. A cross-sectional study was conducted on a representative sample of 6003 Italian adults (18–74 years) in April–May 2020 – reporting information before lockdown and at the time of interview – and two years later (i.e., in February–March 2022). Italian adults using cannabis decreased from 7.0% in pre-pandemic to 5.9% during lockdown (percent change -15.7%) and to 6.7% in 2022 (-4.3%). The reduction was particularly evident among adults aged 55–74 years, whereas cannabis use strongly increased among those aged 18–34 years. In the last period considered (2022), cannabis use was significantly more frequent in men (adjusted odds ratio, OR = 1.43), adults aged 18–34 years (p-trend <0.001), individuals with a low or high level of education (OR = 1.42 and 1.46, respectively), those from Central or Southern Italy/islands (OR = 1.50 and 1.38, respectively), and those with an economic status above the average (OR = 3.07). In 2022, cannabis use was also more frequently reported in current smokers (OR = 3.52), current e-cigarette and heated tobacco product users (OR = 6.09 and 2.94, respectively), individuals with a risky alcohol consumption (OR = 4.60), gamblers (OR = 3.76), those with anxiety and depression (OR = 2.50 and 2.80, respectively), those using psychotropic drugs (OR = 8.96), those with a low quality of life (OR = 1.91), and those sleeping less (OR = 1.42). After the COVID-19 pandemic, cannabis use was more frequent in individuals with other addictive behaviours, and with anxiety and depressive symptoms. [ABSTRACT FROM AUTHOR]