Introduction: In the past century, many studies suggested that LSD-assisted psychotherapy was effective for a wide range of disorders. Nowadays, there is a comeback of psychedelic research, showing again significant therapeutic potential of hallucinogenic substances. Nevertheless, there is a lack of studies with psychedelic-naïve participants. Performing such studies could be important to evaluate possible side effects of LSD. Objectives: We sought to analyze the experiences of first-time LSD consumers in a naturalistic context. Methods: Nine subjects (6 men and 3 women) were collected for the experimental group, and eight subjects (1 man and 7 women) for the control group. The study was conducted in an interand intra-group mixed design of repeated measures. Variables of Personality (EPI A-B), Anxiety (STAI S/T), Depression (BDI-II), Psychopathology (SCL-90-R), and Satisfaction with Life (SWLS) were analyzed. Nonparametric tests were used to analyze the results. Results: Before the LSD experience, differences between groups were found. Experimental group scored significantly higher in Depression (p= 0.03) as well as in certain scales of Psychopathology (ObsessiveCompulsive,p< 0.01; Depression, p< 0.01; Psychoticism, p= 0.01; and Global Severity Index, p= 0.02). Control group scored significantly higher in Satisfaction with Life (p= 0.05). After the LSD experience, several scores of the experimental group decreased significantly, becoming equal between both groups. Most significant decreases were in depression and in psychopathology. Data from the follow-up suggested that these changes were stable over time. Conclusions: First time consumption of LSD in an appropriate context may have benefits to mental health.