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A pattern of mass insanity was discovered to be consequential to the spread of flying parasites. Archaeologists discovered the first evidence of this insanity in studies of the ancient civilizations of Beta Portolan. Around 2066, Levinius V was attacked, and then Theta Cygni XII. In 2265, Ingraham B succumbed, and in 2267, Captain James T. Kirk and the crew of the USS Enterprise discovered the parasites when they attacked the Deneva colony. The parasites inflicted enormous pain on those they infected, and this eventually broke the host's mind. Among those who lost their lives to it were George Samuel Kirk and Aurelan Kirk. As the infiltration spread throughout a planetary population, this effect manifested as mass insanity. Kirk deduced the creature's vulnerability and destroyed them at Deneva, ending the spread. (TOS: "Operation -- Annihilate!")
Mass insanity was the main ill mental effect of the interphase of Tholian space. In 2268, all of the crew of the USS Defiant suffered from this mass insanity and died. A short-time later, the USS Enterprise discovered the USS Defiant adrift in Tholian space. For a brief time, much of the USS Enterprise crew was affected by the interphase and mass insanity started happening. Fortunately for the Enterprise, Chief Medical Officer Leonard McCoy found a cure for the ill mental effects of the interphase in a diluted theragen derivative. (TOS: "The Tholian Web")