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Cannabis has potential therapeutic use but tetrahydrocannabinol (THC), its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities V_max (complexes I, III, and IV activities), V_succ (complexes II, III, and IV activities), V_tmpd (complex IV activity), together with mitochondrial coupling (V_max/V₀), were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H₂O₂) production, measured with Amplex Red. THC significantly decreased V_max (−71%; P < 0.0001), V_succ (−65%; P < 0.0001), and V_tmpd (−3.5%; P < 0.001). Mitochondrial coupling (V_max/V₀) was also significantly …