THC at concentrations found in drivers' blood caused neurotoxicity through oxidative stress in lab cells

THC at 73.75 and 150 ng/mL significantly reduced cell viability (to 76.5% and 64.6% at 48 hours) and caused morphological changes. THC increased reactive oxygen species (peaking at 116.5% at 150 ng/mL), disrupted glutathione balance (GSH/GSSG ratio decreased 69.2%), increased lipid peroxidation (34.5%), and reduced antioxidant enzyme activities. Nuclear condensation and mitochondrial membrane depolarization indicated early apoptosis.

Human undifferentiated SH-SY5Y neuroblastoma cells were exposed to THC at four concentrations (0.66, 20, 73.75, 150 ng/mL) reflecting real-world blood levels found in drivers involved in traffic accidents. Cell viability, ROS, glutathione balance, lipid peroxidation, antioxidant enzyme activities, nuclear morphology, and mitochondrial membrane potential were assessed.

This study bridges the gap between traffic safety data and neuroscience by testing THC concentrations actually found in impaired drivers. The finding that these real-world concentrations cause measurable neurotoxicity provides biological context for why THC impairs driving and other cognitive functions.

The dose-dependent nature of the toxicity aligns with the potency concerns raised by other studies in this database. As cannabis products become more potent, users may achieve higher blood THC levels, potentially reaching the neurotoxic concentrations identified here. This has implications for both driving safety and long-term brain health.

Undifferentiated neuroblastoma cells are not identical to mature neurons. In vitro exposure does not account for blood-brain barrier, metabolism, or protein binding. The concentrations were tested as steady-state exposures, whereas in vivo THC levels fluctuate rapidly. Short exposure times may not reflect chronic use patterns.