Cannabinoids inhibit the respiration of human sperm

Objective: To investigate the effects of the psychotropic compounds Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and Δ⁸-tetrahydrocannabinol (Δ⁸-THC) on sperm mitochondrial O₂ consumption (respiration). Setting: State University of New York Upstate Medical University, Syracuse, New York. Patient(s): Forty-one men who visited the andrology laboratory for fertility evaluation. Intervention(s): None. Main Outcome Measure(s): A phosphorescence analyzer that measures O₂ concentration in sperm suspensions as a function of time was used to measure respiration. Result(s): An immediate decline in the rate of respiration was observed when Δ⁹-THC or Δ⁸-THC was added to washed sperm. The inhibition was concentration dependent, and Δ⁹-THC was the more potent of the two compounds. Respiration was much less affected when Δ⁹-THC or Δ⁸-THC was added to neat semen, suggesting the presence of protective factors in seminal plasma. Both compounds inhibited the respiration of isolated mitochondria, illustrating that direct mitochondrial damage is likely the primary mechanism of action. Conclusion(s): The two main active cannabinoids of the marijuana plant, Δ⁹- and Δ⁸-THC, are potent inhibitors of mitochondrial O₂ consumption in human sperm. These findings emphasize the adverse effects of these toxins on male fertility. The cytoprotective capacity of seminal plasma deserves further investigation.