Young Age and Concomitant Cannabis (THC) and Ethanol (EtOH) Exposure Enhances Rat Brain Damage Through Decreased Cerebral Mitochondrial Respiration.

Abstract

The reason why young people taking concomitantly cannabis (THC) and ethanol (EtOH) are more prone to stroke is underresearched. To investigate whether an underlying mechanism of increased brain damage could be an impaired mitochondrial function, this experiment determined the acute effects of EtOH, both alone and associated with THC, on mitochondrial respiration and oxidative stress (hydrogen peroxide H₂O₂) on young (11 weeks) and middle-aged (45 weeks) brain in rats, using a high-resolution oxygraph (Oxygraph-2K, Oroboros instruments). In young brains, EtOH decreased mitochondrial respiration by -51.76 ± 2.60% (from 32.76 ± 3.82 to 17.41 ± 1.42 pmol/s/mL, p < 0.0001). In 45-week-old brains, the decrease was lesser, but still significant -36.0 ± 2.80% (from 30.73 ± 7.72 to 20.59 ± 5.48 pmol/s/mL, p < 0.0001). Concomitant THC aggravated brain mitochondrial respiration decreases at 11 weeks (-86.86 ± 1.74%, p < 0.0001) and at 45 weeks (-73.95 ± 3.69%, p < 0.0001). Such additional injury was enhanced in young brains (p < 0.01). H₂O₂ production was similar in both age groups (1.0 ± 0.2 versus 1.1 ± 0.08 pmol O₂/s/mL) and was not modified by THC addition. In conclusion, EtOH alone significantly impairs brain mitochondrial respiration and concomitant THC further aggravates such damage, particularly in young brains. These data support the hypothesis that enhanced mitochondrial dysfunction might participate in the increased occurrence of stroke in the young and urge for better prevention against EtOH and THC addictions in adolescents.