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Abstract Background Medical cannabis, legalized in many countries, remains illegal in France. Despite an experiment in the medical use of cannabis that began in March 2021 in France, little is known about the factors associated with the use of cannabis for self-medication among adults. Methods Data came from the French TEMPO cohort and were collected between December 2020 and May 2021. Overall, 345 participants aged 27–47 were included. Cannabis for self-medication was defined using the following questions: ‘Why do you use cannabis?’ and ‘In what form do you use cannabis?’. The penalized regression method “Elastic net” was used to determine factors associated with the use of cannabis for self-medication, with the hypothesis that it is mainly used for pain in individuals who have already used cannabis. Results More than half of the participants reported having ever used cannabis (58%). Only 10% used it for self-declared medical reasons (n = 36). All self-medication cannabis users, except one, were also using cannabis for recreational purposes. The main factors associated with cannabis use for self-medication vs. other reasons included cannabis use trajectories, the presence of musculoskeletal disorders, tobacco smoking, and parental divorce. Conclusions Engaging in cannabis use during adolescence or early adulthood may increase the likelihood of resorting to self-medication in adulthood. Due to the propensity of individuals with cannabis use during adolescence to resort to uncontrolled products for self-medication, this population should be more systematically targeted and screened for symptoms and comorbidities that may be associated with cannabis use.