The OCCSA billboard illustrates how badly skewed current policies toward substances are, in light of the actual harm caused by the different substances. The legal drugs alcohol and tobacco have an enormously greater medical impact on society than all of the illegal drugs combined, and alcohol plays the principal role in substance-related violence and other criminal activity.
A common response made to this point by prohibitionists (and other unconvinced citizens) is to call that a reason to keep the illegal drugs illegal -- do we want to have such huge problems with those drugs too, as we have with the legal drugs? While this argument doesn't answer to the disparate resources applied in, say, drug education vs. tobacco and alcohol education, it does evoke the fear of a "nation of addicts" that stands in the way of drug policy reform.
There are at two fundamental flaws to their argument. First, they are comparing certain drugs that are legal, with _other_ drugs that are illegal. Different drugs have different effects, different use patterns, different sociological associations and different interactions with policies. One needs to look at legal alcohol vs. prohibited alcohol, for example, or legal opiates before 1914 vs. a war on heroin today, or Dutch marijuana coffeeshops vs. marijuana arrests every 49 seconds in the U.S., to make a valid comparison. Not that the analysis stops there -- one needs to also look at differences between times, countries, cultures, circumstances, etc. But at least we then have the beginning of a reasonable comparison.
Secondly, the argument entirely omits the fact that drugs, both legal and illegal, do not exist in isolation from one another. Alcohol use patterns are not independent from marijuana use patterns are not independent from use of other drugs. For example, increasing marijuana use may be associated with decreasing use of alcohol, or vice-versa. While it is conceivable that experimentation with or even longer-term usage of the currently illegal substances could increase following legalization, it is not at all clear that overall intoxication from all substances combined would increase -- especially given the fact that the illegal drugs currently are widely available despite prohibition, and can be purchased by high school and junior high school students at school, from other students.
The argument that use of and harm from the currently illegal drugs would skyrocket to the level of use and harm of the currently legal drugs, implies that legality is the defining factor determining their level of use -- that is, all legal drugs are going to be used at approximately the same rate or order of magnitude. But the same type of reasoning should then imply that all illegal drugs would be used at the same level as well.
We know, however, that different illegal drugs are not all used at the same rate. Marijuana is enormously more popular than heroin, cocaine, LSD and methamphetamine combined. It's not that marijuana is legal where the other drugs aren't, and it's not that the marijuana laws go unenforced. (Remember, one arrest every 49 seconds.) Fewer people use heroin or cocaine, because heroin and cocaine are scary and are widely understood to be dangerous. There's simply no basis for the belief that scary drugs like heroin or cocaine, at least in their current, highly intense forms, would ever be as widely used even as marijuana, let alone alcohol.