BACKGROUND The features of acute classical recreational drugs or new psychoactive substances (NPS) toxicity fall into three broad groups: (i) stimulant; (ii) hallucinogenic and (iii) depressant. Currently, there is no information available on healthcare professionals knowledge/confidence in managing the acute toxicity related to NPS use. AIM We have compared knowledge and confidence of managing acute toxicity related to use of NPS with that seen with the use of to classical recreational drugs. DESIGN AND METHODS Physicians/nurses completed a questionnaire survey to self-assess on a 5-point scale their knowledge (1-little knowledge; 5-very knowledgeable) and confidence (1-little confidence; 5-very confident) of managing acute toxicity related to the use of classical recreational drugs or NPS. Differences between knowledge and confidence for classical recreational drugs and NPS were assessed using paired Student's t-test; comparison between doctors, nurses and the frequency of managing acute classical recreational drug/NPS toxicity was assessed using unpaired Student's t-test. RESULTS One hundred and eighty-eight (82 physicians, 106 nurses) completed the survey. Classical drug compared with NPS knowledge: nurses 2.9 ± 1.0 vs. 2.1 ± 1.0, P < 0.001; physicians 3.1 ± 0.8 vs. 2.1 ± 1.0, P < 0.001. There was no difference between nurses and physicians in classical drug (P = 0.11) or NPS (P = 0.89) knowledge. Confidence in managing classical drug toxicity compared with NPS confidence: nurses 3.0 ± 1.1 vs. 2.3 ± 1.1, P < 0.001; physicians 3.0 ± 0.9 vs. 2.1 ± 1.0, P < 0.001. There was no difference between nurses and physicians in classical drugs (P = 0.85) or NPS (P = 0.33) confidence. CONCLUSIONS Physicians/nurses are less confident in managing acute NPS toxicity. Management of toxicity is not dependent on knowing the drug/NPS, but should be on the basis of these clinical signs/symptoms. Training/education should focus on the concept of managing the pattern of toxicity that an individual presents with rather than the actual drug(s).