Disclaimer: All thoughts and advice expressed are the personal opinions and gatherings of the author and do not constitute medical advice. If you are seeking medical advice please consult a doctor.

The first thing is using pure Proglumide, people often turn to other chemicals out there that have part Proglumide or metabolizes into Proglumide. An example of this is Proglumetacin (brand name Afloxan, Protaxon and Proxil), this breaks down into both Proglumide and  Indometacin – an NSAID (non steroidal anti inflammatory). Indometacin is toxic to renal function during prolonged use, a side effect not ideal for reducing tolerance in the long term. So you want pure Proglumide, this is rather hard to find as Proglumide is a redundant drug in the medical world – and it won’t be surprising that nobody will be producing this stuff in a few years time, and we won’t be able to supply it either without having our own lab.

Note to readers : To avoid confusion – Proglumide does not contain Indometacin at all. It is Proglumetacin (another medication) that changes into both the toxic Indometacin and Proglumide in the body.

The second thing is dosage and what strategy to employ, as tolerance to Proglumide does develop. This excerpt from the web based on Watkins LR, Kinscheck IB, Mayer DJ. Potentiation of opiate analgesia and apparent reversal of morphine tolerance by proglumide. Science. 1984 Apr 27;224(4647):395-6.

Proglumide is not some sort of magic bullet for completely eliminating the risk of tolerance development and addiction as its effects are only effective for a limited duration before tolerance to IT begins to develop. (After 8 days its effectiveness begins to wane) The work of Kellstein & Mayer 1990 suggests that successful therapeutic/maintenance applications will probably require its discontinuation for a week after each week of use. More work is needed to better define the precise parameters of its effective use for this purpose.

This shows that a surefire way to fail Proglumide is abusing its opiate anti tolerance effect on a daily basis. What we want to do is to take it intermittently, either a week on and a week off, or 3 days on and 3 days off, or ideally one day on and one day off you want to give 50% time off being off Proglumide.

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The dosage recommendation anecdotally is 150mg to 300mg (in the study of Watkins it is said to be 200 to 250mg). I cannot emphasize more the importance of not allowing Proglumide tolerance to develop, in the long term it will be more rewarding for you. It is also beneficial for those attempting to mediate opiate tolerance by periodically reducing or not taking their opiate dosages for a week or two. Though understandably for those with large tolerances or constant pain this may be difficult. It would be useful to do whilst Proglumide is lowering tolerance on the side to not be harassing your opoid receptors with large amounts of agonists.

My advice would be to use on a one week on and one week off basis . Proglumide will work with any opioid as it inhibits the production of CCK which is universal to all opioids. It is ESSENTIAL that one realises that indometacin is toxic if used for a prolonged period of times. Renal and to a certain extent neuro toxicity has been noted after chronic use.- Starfarer, Bluelight

Approved dosages for Proglumide, for managing ulcers is 400mg 2 to 4 times daily, up to 800mg 3 times a day. This dosage is used to manage ulcers, not for the purposes of managing tolerance, but it gives you a good ideal of the upper ceiling of what you can take.

The third thing is how to take it, it is generally recommended to take it independently of opiates, Proglumide as mentioned in the previous article is not a potentiator (though it can function like one), it is a tolerance reducer. If you are taking it with opiates, do take it at least 60 minutes before ingesting the opiates, this will give time for the Proglumide to achieve its CCK inhibitory effects on your nervous system.

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Finally Proglumide shouldn’t be used to “increase the high” or be “high all the time” or “recreating the euphoria”, while its possible to use it for such end goals, tolerance to Proglumide will eventually develop if its abused very quickly and you will be back to square one. The key against tolerance to any chemical apart from  how reactive your body and mind is to tolerance, is low dosage and time gaps (breaks). Raising the dosage of proglumide might yield you good short term results, but in the long term your body will develop a tolerance to it. The best way to use Proglumide is to mediate/reduce the dosage needed for your opiates to achieve pain relief, or whatever other use you have in mind. As with all depressants, the higher the opiate dosage the more side effects and the less positive effects occur.

CCK is also implicated in other psychostimulant pathways, it is possible that proglumide can reduce the tolerance of other substances, and also possible that abusing other psychostimulants of a different class of drugs rather than opiates could reduce proglumides effectiveness as well in opiate tolerance reversal.

I should note that there is very good evidence that the brain is pretty much wired to develop tolerance to euphoria no matter what, because it is the last thing you want chronically for survival, that’s why chemical induced euphoria quickly loses its magic after the first few rounds, because the brain simply isn’t designed to experience happiness in that way.

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Proglumide and Reducing Opioid Tolerance – A Summary

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