I knew about cimetadine, and grapefruit juice,,,,BUT, this . . .

Another interesting comment was made by Karl Jansen (2001) concerning the administration of small oral doses of ketamine being found to be of use in chronic pain clinic for "greatly reducing" the development of tolerance (via blockade of NMDA receptors).

However, many people are unaware that both enhanced effectiveness of narcotic analgesics AND prevention or reversal of tolerance is readily achievable through the oral use of up to 200-250 mg of Proglumide [(DL)-4-Benzamido-N,N-dipropylglutaramic acid]. [See Ott 1999; Watkins et al. 1984]

The work of Watkins suggests there may be a therapeutic dosage window with diminished results above it but more detailed work to define this is apparently lacking.

Rather than simply augment the action of the opiates, proglumide actually interferes with the anti-opioid activity of the neuropeptide CCK.

The chronic administration of opiates, or spinal cord and other CNS injuries, elevates the level of Cholecystokinin (CCK) that is present. Such elevated levels exert an antagonistic effect on opioid activity resulting in significantly diminished analgesic effects. (Watkins et al. 1984; Xu et al. 1993 & 1994)

It is this rise in CCK levels that directly leads to the condition known as drug tolerance and the corresponding increase in its anti-opioid activity that requires the opiate user to use increasingly larger amounts to achieve the same effects.

This anti-opiate effect can be prevented or even reversed through the administration of CCK inhibitors such as proglumide. (Watkins et al. 1984)

Besides just interfering with the adverse action of CCK on opiate activity, proglumide is also known to augment the analgesic effect of opiates. Often this can provide a higher quality of analgesia for those patients who suffer from an incomplete response to pain medications.

Watkins & coworkers reported that proglumide reversed morphine tolerance and also 1) hastened the onset of analgesia, 2) increased the peak levels, and 3) prolonged the duratio

I'm sure some f(r)iends here may know more . . .most drug forums are filled with fuckwits (imo!)   BUT......anyone here know more? jon?

f1

Yes, I think there are a number of combo's which are hardly, or not at all well known.

Not even most pain doctors know of this one, and as I look further into it, I see its actually OLD news! And the "no tolerance" effects only last about a week, however, before ones tolerance starts to rise, albeit far more slowly, and if used every second week (as in one week on, then one week off,or there abouts) it seems to be quite effective in maintaining dose "strength" as well as slowing down 'escalating tolerances' significantly!

However, Karl Jannsen is of the "Janssen Pharmaceuticals" fame, the fathers of Fentanyl, and I cant see how this type of "knowledge" increases sales of the narcotics they(and the others) sell,
 and as Pharma sales reps, are often "providing doctors" with data about "new improved drugs" when patents run out, and IMO are UNLIKELY to provide Drs with data which REDUCES "product sales" by increasing their effectiveness!

 And many doctors just aint that interested in using "old" technology!

But, there's no doubt that "pro-drugs" are here to stay, which IMO is a good thing.

Thanx Baba, for the data, even though people can metabolize things quite "differently" e.g. well, or poorly, or in some cases, not at all! So your pov is appreciated for (obviously) reference purposes only, (and probably best used on plants!)

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