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Background Cannabis has increasingly been used for medical and recreational purposes. The main pharmacological compound in cannabis is tetrahydrocannabinol (THC), which has sedative, anxiolytic and analgesic effects. In some animal models, THC has also been shown to reduce the minimum alveolar concentration (MAC) of halothane and cyclopropane, but its effect on sevoflurane, currently the most commonly used inhalational anaesthetic agent, has not been investigated. Objective To investigate the effect of THC on the MAC of sevoflurane in rats. Methods Observer-blinded, randomised controlled trial. Setting Centre for Biomedical Research of the Medical University of Vienna, 2019. Individuals Thirty-eight adult Wistar rats. Interventions The rats were allocated randomly into one of two groups. Group A received THC 10 mg kg and group B received the corresponding volume of placebo via gastric gavage (administration through a tube placed in the distal oesophagus). The rats were then individually anaesthetised in an airtight sevoflurane-flooded chamber, and the MAC in both groups was determined using Dixon's up-and-down method. Blood samples were drawn to measure serum concentrations of THC. Main outcome measures The primary outcome was the MAC of sevoflurane in Groups A and B. Results The bootstrap estimate of the MAC of sevoflurane was 2.1 (95% confidence interval 1.8 to 2.4) vol% in the THC group and 2.8 (95% confidence interval 2.7 to 2.9) vol% in the placebo group, corresponding to a significant MAC reduction of 26% in response to THC. Conclusion Gastric administration of THC 10 mg kg significantly reduced the MAC of sevoflurane by 26%. Trial registration Not applicable.

BACKGROUND Generic drug preparations do not require the same degree of scrutiny as the originally licensed preparation before they can be approved for clinical use. The permitted tolerance limits for bioequivalent preparations might be associated with clinically relevant differences for drugs with a narrow therapeutic index, such as local anaesthetics. OBJECTIVE We compared pharmacokinetic and pharmacodynamic characteristics of generic and reference listed or original preparations of ropivacaine. DESIGN The current healthy volunteer study used a randomised, triple-blinded, cross-over equivalence design. SETTING Tertiary university hospital, Medical University of Vienna. SUBJECTS Healthy male volunteers (N=18) aged 18 to 60 years. INTERVENTIONS A series of three ultrasound-guided ulnar nerve blocks separated by at least 6 days were carried out on each volunteer. Reference listed ropivacaine (NaropinTM) was used for two blocks and a generic preparation of ropivacaine was used for the other block. Sensory block onset and duration were evaluated using loss of pinprick sensation. MAIN OUTCOME MEASURES Duration of sensory block was the primary outcome. Secondary outcomes included time-to-onset of sensory block, ropivacaine pharmacokinetics from venous blood samples and pH of the preparations. Equivalence was evaluated using the ratios of means and 90% confidence intervals (CIs) of log transformed data. RESULTS Equivalence was demonstrated for the primary outcome measure, the duration of sensory block [original : generic ratio 1.01 (90% CI 0.87 to 1.16); P