Elevated serum levels of creatine kinase enzymes have been found in brain injuries and psychosis. Cannabinoid use is associated with increased frequency and duration of hospitalizations. We examined whether creatine kinase levels differ in psychotic cannabinoid users and the association between creatine kinase levels and clinical measures (duration of hospitalization and need for mechanical restraint). Computerized medical records of 124 men hospitalized due to acute psychotic episodes were reviewed. Creatine kinase levels and various clinical measures at admission were documented. Cannabis users were significantly younger than nonusers. Duration of illness was longer among nonusers. Log creatine kinase among cannabinoid users (N = 32) was numerically higher compared to nonusers (N = 92) (5.6 ± 1 vs. 5.2 ± 0.9, respectively). Significantly higher rate of elevated creatine kinase levels (creatine kinase > 195 U/l) was detected in the cannabinoid users compared to nonusers (59.4% vs. 38%, respectively; P < 0.04). No association was found between creatine kinase levels and use of mechanical restraints and hospitalization days. Higher rate of elevated creatine kinase levels was observed in hospitalized psychotic cannabinoid users, possibly due to a cannabis activity at peripheral or brain tissues. Studies in larger, more diverse clinical populations are needed to confirm this finding and to clarify the biological mediators of elevated creatine kinase levels in psychotic cannabinoid users.