Because these drugs are designed to have an altering effect on perception, emotion, or behavior, the damage done to the brain could be at a level that does not have any relationship to the limited cognitive functioning of a mouse brain.
You are quite right. Since my expertise is pharmacokinetics and metabolism, and since the subject here seems to be as much about safety as efficacy, I confined my comments to that area, but the CNS area is one of the hardest in which to do origial (not me-too) pharmacological research.