The paper evaluates the prevalence of psychoactive substance use in a non-clinical sample of university students and examines its relation to childhood traumatic experiences and common mental health problems. An anonymous online survey was conducted between September 2022 and May 2023 in two major universities in Bulgaria using opportunity sampling. The study has a cross-sectional, observational, and retrospective design, using self-rating scales for depression, anxiety, alexithymia, empathy, quality of life, and lifetime history of substance use. One hundred and forty-six university students completed the survey, with a mean age of 23 years (SD=2), 66% females. Ninety-eight percent of the participants have used caffeine, 90% alcohol, 62% tobacco, 50% cannabis, 26% sedatives, 19% amphetamines, 12% inhalants, 8% hallucinogens, 4% opiates, and 9% other/unknown substances. The mean number of psychoactive substances used within a lifetime is 4 (SD=2). Forty-two (29%) participants have a history of use of multiple (≥ 5) types of psychoactive substances. Statistically significant differences from the rest of the sample include lower empathy (p=.016), higher scores on the childhood trauma scale (p=.001), and a higher percentage of dissociative symptoms (47.6%, p=.012). The binary logistic regression model revealed that higher scores on the childhood trauma scale (p=.003) and lower empathy (p=.004) are statistically significant predictors of multiple substance use. In conclusion, the lifetime use of multiple psychoactive substances in non-clinical settings is related to underlying childhood traumatic experiences and lower empathy.