The major psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), strongly affected rat liver mitochondria in vitro. At concentrations of 15-60 nmoles/mg of mitochondrial protein, THC uncoupled state IV respiration and decreased respiratory control and ADP/O ratios. Energy-linked changes in fluorescence of 8-anilino-1-naphthalene sulfonate were prevented or reversed by THC. THC also produced large amplitude swelling of mitochondria and release of matrix enzymes. These effects were greatly potentiated by Mg2+. Likewise, flocculation of mixed phospholipid micelles by Mg2+ was potentiated greatly by low concentrations of THC. Studies with micelles prepared from purified phospholipids suggest that THC may specifically destabilize the cardiolipin in mixed micelles.
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