On the topic of the (Recreational) Drug That Most Changed the World, the six up for consideration between Craig and the panelists - Columbia University professor David Eisenbach, comedian Derek Waters and actor Maria Bello - are: alcohol; cocaine; L.S.D.; performance enhancing drugs; marijuana; and caffeine. Beyond the merits of each drug having most changed the world, the panel discusses their own personal history with each of the drugs in question. They also discuss the links of some of these drugs to prescription medications, the resulting moral aspects that each drug has taken in social culture, and the effect of the drug being legal or not into the view of that morality. They also mention drugs that did not make the list but perhaps should have, including one that may not yet be considered as such in mainstream society.