The effect of oral Δ-9-tetrahydrocannabinol on the minimal alveolar concentration of sevoflurane

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.