Despite the documented negative cognitive effects of heavy marijuana use in adolescence [42,50,57], animal studies examining potential neuroprotective effects of cannabinoids (the active ingredient in marijuana) on toxic insults suggest antioxidant properties and reductions in glutamate excitotoxicity in the brain by inhibition of glutamate transmission [37,38,55,102]. As excitotoxicity and oxidative stress are suggested mechanisms of alcohol-related brain injury [24,25], cannabinoid exposure could potentially mitigate ethanol-induced changes[36]. However, a study of neonatal rats found that activation of endocannabinoid CB1 receptor, in combination with alcohol administration, may modulate glutamate and GABAergic neurotransmission, and prime the brain to suffer cell death by suppressing synaptic activity important for developmental processes. This could indicate that alcohol and marijuana use together may lead to worse neural outcomes, specifically in the developing brain [40].
