Glutethimide (Doriden) was introduced in 1954 and methaqualone (Quaalude, Sopor) in 1965 as safe barbiturate substitutes. Experience showed, however, that their addiction liability and the severity of withdrawal symptoms were similar to those of barbiturates.

By 1972, "luding out," taking methaqualone with wine, was a popular college pastime. Excessive use leads to tolerance, dependence and withdrawal symptoms similar to those of barbiturates. Overdose by glutethimide and methaqualone is more difficult to treat than barbiturate overdose, and deaths have frequently occurred. In the United States, the marketing of methaqualone pharmaceutical products stopped in 1984 and methaqualone was transferred to Schedule I of the CSA. In 1991, glutethimide was transferred into Schedule II in response to an upsurge in the prevalence of diversion, abuse and overdose deaths.