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[axeman157]

I'm guessing heroin, due to how Dwarf Fortress can be surprising, who would want a heart attack? 

[Jervous]

All of them. Drugs are bad, mkay.

[Jeoshua]

There's seriously not a good one.

PCP would be the absolute worst, in my opinion.  The HFS would probably send you into a fearful, homicidal rage.

Best would have to be Adderall or any speed-based drugs.

[Putnam]

Yeah, pretty much any stimulant would be pretty horrible.

[NW_Kohaku]

Yeah, pretty much any stimulant would be pretty horrible.

*sips coffee*

Really?  Helps keep me going.

[Putnam]

Yeah, pretty much any stimulant would be pretty horrible.

*sips coffee*

Really?  Helps keep me going.

Meaning a stimulant on a higher level than "keeps you going", of course.

[Vanaheimer]

A strong hallucinogenic. Think LSD or peyote. You'd be seeing little midgets flying through your walls on fire.

[Kilroy the Grand]

I'd say something like barbiturates, you'd fall asleep and you're fort would crumble to it's end.

[Dae]

It may very well be a urban legend, but I heard angel dust (PCP) was absolutely goddawful. Some guy apparently took some then broke a mirror and used the glass shards to *cut his face into a lot of little parts before ripping them off*. He apparently proceeded to feed the flesh to his dogs.

In a normal context.
Imagine what that could do if presented with the madness of Dwarf Fortress.

[NW_Kohaku]

It may very well be a urban legend, but I heard angel dust (PCP) was absolutely goddawful. Some guy apparently took some then broke a mirror and used the glass shards to *cut his face into a lot of little parts before ripping them off*. He apparently proceeded to feed the flesh to his dogs.

In a normal context.
Imagine what that could do if presented with the madness of Dwarf Fortress.

DF is only madness because you are trying to understand what is going on.

PCP or LSD would, seriously, just reduce DF to a bunch of flashy lights with no particular meaning.  In fact, LSD would probably have you smelling or feeling the flashy lights (crosses the wires of your senses), which would probably make it somewhat painful. 

Showing DF to someone in that frame of mind would be like showing someone a book in a language with a totally different alphabet than the one they understand - they wouldn't be able to tell the difference between the raving confessions of a mass murdering cannibal from a recipe to bake a pie. 

[lordcooper]

I tried to play DF once while coming down off LSD.  It didn't make much sense.  The tiles were wavy and there seemed to be a few more colours on my screen than actually exist.

To actually answer the OP; probably any form of moderately strong stimulant.  Mainly due to the difficulty in remaining still.  Ketamine and similar downers would also provide a fair bit of difficulty because they tend to make reading (or focusing on anything at short range) fairly unpleasant in my experience.

Why the weird question?

[EveryZig]

they wouldn't be able to tell the difference between the raving confessions of a mass murdering cannibal from a recipe to bake a pie.

If Sweeny Todd is involved it might be both.

[JackOSpades]

I'm going with Sobriety and or Sanity 

[RabblerouserGT]

There's seriously not a good one.

PCP would be the absolute worst, in my opinion.  The HFS would probably send you into a fearful, homicidal rage.

Best would have to be Adderall or any speed-based drugs.

Oh god.. I had a druggie friend of a friend have a baaaaaaad trip "watching" Metalocalypse... guy was screaming.

Worst I can think of with DF is scary.. letters, unless we're talking tilesets.

[Dae]

Showing DF to someone in that frame of mind would be like showing someone a book in a language with a totally different alphabet than the one they understand - they wouldn't be able to tell the difference between the raving confessions of a mass murdering cannibal from a recipe to bake a pie.

Yes, but if you play DF I assumed the drug taker would already know how to play.
It might be interesting to ask an experienced player to take various drugs and start a fort on the same map under influence, to compare the effect of drugs on the mind of the average DF player. In a science context of course, with security staff, recording and all that. There were studies where artists were asked to draw a self-portrait every hour or so after taking drugs.