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BACKGROUND: The last decade has seen the appearance of myriad novel psychoactive substances with diverse effect profiles. Synthetic cannabinoids are among the most recently identified but least researched of these substances. METHODS: An anonymous online survey was conducted in 2011 using a quantitative structured research tool. Missing data (median 2%) were treated by available-case analysis. RESULTS: Of 14,966 participants, 2513 (17%) reported use of synthetic cannabis. Of these, 980 (41% of 2417) reported its use in the last 12 months. Almost all recent synthetic cannabis users (99% of 975) reported ever use of natural cannabis. Synthetic cannabis reportedly had both a shorter duration of action (z=17.82, p<.001) and quicker time to peak onset of effect (z=-9.44, p<.001) than natural cannabis. Natural cannabis was preferred to synthetic cannabis by 93% of users, with natural cannabis rated as having greater pleasurable effects when high (t(930)=-37.1, p<.001, d=-1.22) and being more able to function after use (t(884)=-13.3, p<.001, d=-0.45). Synthetic cannabis was associated with more negative effects (t(859)=18.7, p<.001, d=0.64), hangover effects (t(854)=6.45, p<.001, d=0.22) and greater paranoia (t(889)=7.91, p<.001, d=0.27). CONCLUSIONS: Users report a strong preference for natural over synthetic cannabis. The latter has a less desirable effect profile. Further research is required to determine longer term consequences of use and comparative dependence potential.