Loperamide is a really odd one. Janssen went to great lengths to design a perpherally acting opioid with the analgesic activity appearing at a dose some x615 that of it's primary activity.
It isn't well researched at high doses but from what I know, it's actively transported out of the brain and it's only when that active transport is overwhelmed that it becomes centrally active. But the specific dose at which it overcomes the active transport which in turn results in a nasty 2-phase dose-response curve.
I've known people who were taking 200mg/day and were fine only for 240mg to see them in the ICU.
But it's unclear if there is a rate-limited metabolic step so that the stated 11.5 hour half-life might also differ widely between users.
I can well understand why being on a mission every damned day gets to a person but it seems so little is known that no detoxification protocol exists. It seems while case studies quite often turn up, it isn't common enough for a single research group to collect data from a large enough cohort to provide concrete data.
