Aims This study aimed to evaluate the acute effects of cannabidiol plus tetrahydrocannabinol (CBD+THC) and tetrahydrocannabinol (THC) oils on cardiovascular haemodynamics, respiratory muscle activity and peripheral tissue perfusion in healthy adults. Methods In this randomized, double-blind, crossover trial, participants received orally administered CBD+THC oil (12.5 mg + 12.5 mg), THC oil (12.5 mg) or placebo. Cardiovascular haemodynamics, respiratory muscle electromyography and peripheral tissue perfusion were evaluated during breathing tasks. Results Eighteen individuals were evaluated (26 ± 5 years). Both oils significantly increased heart rate (HR) (p textless 0.05). Cardiac index significantly increased in I-THC at 60 and 150 min postdose (p textless 0.05). The vascular resistance index was lower in the I-THC, with significant differences during respiratory overload and recovery (p textless 0.05). A significant increase in activity of the sternocleidomastoid (SCM) and parasternal (PARA) muscles was observed in the I-THC during inspiratory loading at 60 and 150 min after dose (p textless 0.05). In the I-CBD+THC, increased activation was observed in the scalene (ESC) and PARA muscles (p ≤ 0.021). HHb levels showed a descriptive decrease, particularly during inspiratory loading and recovery in the I-THC group, without reaching statistical significance, whereas O2Hb showed a significant increase during inspiratory loading in the I-THC group (p textless 0.05). Conclusions Acute administration of THC and CBD+THC oils induced distinct cardiorespiratory responses in healthy individuals, affecting cardiovascular haemodynamics, respiratory muscle activation and peripheral tissue oxygenation. THC produced more pronounced physiological responses, while CBD+THC was associated with a more attenuated pattern.