Because alcohol is a depressant, which drug would be the most harmful when used with it?

Combining alcohol with another depressant such as opioids (e.g. heroin, oxycodone) or benzodiazepines (e.g. Xanax, Valium) can have extremely dangerous and potentially deadly effects, as both substances can slow down the central nervous system and respiratory system. Mixing alcohol with these substances can increase the risk of overdose, respiratory depression, and other serious health complications. It is important to always seek medical advice before combining alcohol with any other drugs.