The Fremen knew of the effects of the Water of Life and used it to make their Reverend MOthers. They were taught this by a Reverend MOther in extremis following the Missionaria scheme (JEssica guesses). BEfore that other drugs were always used. However once they discovered how effective the Water of Life was no other drugs could match. Also, if a Reverend MOther was made one via Water of Life she couldn't be influenced by the other drugs. During Leto's reign the Reverend MOthers sometimes used the other drugs because they had a short supply of melange but it was comparatively ineffective. BAsi