During the past few years, efavirenz has been increasingly used in the treatment of HIV1 infection. Its main side effect is a syndrome of central nervous system stimulation occurring in 40-50% of adults in the first few weeks of therapy which might be observed at increased frequency in subjects concurrently using recreational substances. We therefore conducted a single center, retrospective study in 134 patients treated with efavirenz and found no significant differences in CNS side effects or discontinuation rates between recreational substance (cocaine, ecstasy, cannabis) users and non-users. Although our study is limited, the results support the idea that efavirenz can be safely prescribed to patients using recreational substances.