INTRODUCTION: The effects of cannabis use on the autonomic regulation of the heart had been identified in tests with volunteers. We studied these effects of cannabis use on young adults in everyday life. METHODS: We measured heart rate variability (HRV) and well-being (WHO-5 score) in young men during a routine medical examination. Seventy-two men were identified with a positive drug screening test solely for tetrahydrocannabinol. The comparison group consisted of 72 men, matched according to age and body mass index, who used no illicit drugs or pharmaceuticals. RESULTS: In the cannabis group, HRV was significantly increased compared to the control group. The median value of root mean square of successive differences (RMSSD) at rest was 56.2 ms in the drug users and 48.6 ms in the controls (p<0.05). The ratio of low-to-high frequency was higher in the controls (median 1.87 vs. 1.62; p<0.05). Psychological well-being, measured by WHO-5 score was significantly lower in cannabis users. DISCUSSION: Our data support the hypothesis that the use of cannabis leads to a change in cardiovascular sympathovagal balance.