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How To Order / Buy Proglumide OTC Online Here

We no longer sell Proglumide in public.  Please e-mail us at support@khemcorp.com for more details. We have a private list we provide bulk Proglumide with.

Proglumide is over the counter class medicine and is totally legal, still we don’t want people to see this website as an online pharmacy, which is why we no longer sell to the public. We can connect people to quality Proglumide.

We have Proglumide in stock available right now, and delivery can be made as fast as the next day. Please e-mail us at support@khemcorp.com to get connected and registered.

In the meantime checkout our Proglumide calculator here, this is based off the research we have done and is not any kind of professional medical advice.

Click here for the Certificate of Analysis. (STC is no small testing enterprise, we paid good money for the testing) Here is their about page.

If you want your Proglumide on time, we highly (emphasize highly again), recommend you go with the EMS (Tracking Courier) option, instead of standard airmail.
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What is Proglumide?

Proglumide Reversing Opiate Tolerance – A Comprehensive Review of Administration  New Article!

How to Reduce Opiate Tolerance
Proglumide and Reducing Opioid Tolerance – A Summary

Proglumide Dosage, Tolerance and Strategy – A Simple Guide to Mediating or Reducing Opiate Tolerance
Proglumide – Anecdotal Experiences from the Internet
Herbal Supplements that Help Dealing with Tolerance and Withdrawal

Below is for search (sorry for the clutter, I am not a web designer)

Chemical Structure of the Opoid Tolerance Reduction Chemical Proglumide

Chemical Structure of  Proglumide

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 duration. They suggested that not simply did this indicate that effective narcotic doses could be decreased but it also indicated that proglumide might be able to enhance the effects of other procedures, such as acupuncture, which involve endogenous opiates. (Watkins et al. 1984) Proglumide is a nonselective CCK inhibitor that was formerly employed as an anti-ulcer medication (Hahne et al. 1981). It shows NO analgesic effects of its own. Although proglumide is now considered to be an obsolete pharmaceutical due to changes in our understandings of ulcer etiology, it has already seen extensive pharmacological and toxicological testing proving its safety and has been approved for use in humans. It has largely fallen into disuse but is still available in bulk via chemical houses or as a pharmaceutical in Europe and Africa sold under the trade name Milid and Milide. Other CCK inhibitors show similar properties (Idänpään-Heikkilä et al. 1997; Xu et al. 1993). However, beyond simply having seen previous use in humans, proglumide is both inexpensive and nontoxic. (Ott 1999) 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. Despite this, proglumide has already demonstrated itself to be of value both in pain management and as an adjunct to maintaining a narcotic addiction within a larger program of harm reduction (Anonymous 2000; Ott 1999). What is fascinating is how few drug educators, drug treatment facilities or even drug users are aware of this despite it being readily available information for nearly 20 years. If development of tolerance and the high price of a sustained addiction are truly as serious of a problem as we all agree that they are, one can only wonder how it is that, despite the tools existing to remove or at least reduce this problem, there seems to be no interest or research except on a limited scale related to specific small areas of chronic pain management and understanding. The current misguided approach of substituting methadone is commonly reported to actually cause MORE perceptual and thinking problems than the opiates it replaces PLUS methadone is known to cause physical damage to internal organs that are not encountered with opiate use itself. Harm reduction approaches would benefit greatly by using proglumide as a cornerstone and making it readily available to both narcotic users and abusers. Those who will most certainly object include organized crime and drug dealers who enjoy the obscene profits reaped from escalating drug tolerances, and possibly also the so-called “drug educators” that sadly often seem to be the ones most in need of some factual education. There are many problems associated with opiate use and abuse. While the majority of these are legal in origin, the most sensible approach would be to ameliorate [or mitigate] those that aren’t. Increased analgesic effectiveness and prevention of tolerance are two obvious areas where harm reduction is readily possible TODAY. Both sufferers of chronic pain and narcotic addicts stand to benefit from having their needs met and their health risks simultaneously decreased. As this is first and foremost a health problem, the current approach of harm maximization is both counterproductive and unacceptable. To a rationale or caring mind it might even be perceived of as unethical and amoral. Not only do sufferers of chronic pain and narcotic addicts stand to benefit from such harm reduction approaches but, by decreasing drug-associated crimes, a significant area of the true “drug problem” can be directly addressed, thereby benefiting society as a whole.

References:

Ameer, Barbara & Randy A. Weintraub (1997) Clinical Pharmacokinetics 33 (2): 103-121. “Drug Interactions with Grapefruit Juice.”Anonymous (2000 & 2001) Personal interviews with assorted opiate users & abusers. Caraco, Y. et al. (1996) Drug Metab. Dispos. 24(7): 761-764. “Microsomal codeine N-demethylation: cosegregation with cytochrome P4503A4 activity.” [Y. Caraco, T. Tateishi, F.P. Guengerich & A.J. Wood] [Abstract from PubMed] Crain & Shen 1996: See patent references farther below. Crain, Stanley M. & Ke-Fei Shen (2000) Pain 84: 121-131. “Antagonists of excitatory opioid receptor functions enhance morphine’s analgesic potency and attenuate opioid tolerance/dependence liability.” Dresser, G.K. et al. (2000) Clinical Pharmacokinetics 38(1): 41-57. “Pharmacokinetic-Pharmacodynamic Consequences and Clinical Relevance of Cytochrome P450 3A4 Inhibition.” [George K. Dresser, J. David Spence & David G. Bailey] Entheogen Review; POBox 19820, Sacramento, CA 95819-0820. [www.entheogenreview.com] Feierman DE, & J.M. Lasker (1996) Drug Metab. Dispos. 24(9):932-939. “Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. Role of CYP3A4.” [Abstract from PubMed] Hahne, W.F. et al. (1981) Proceedings of the National Academy of Science (USA) 78 (10): 6304-6308. “Proglumide and benzotript: Members of a different class of cholecystokinin receptor antagonists.” [W.F. Hahne, R.T. Jensen, G.F. Lemp & J.D. Gardner] Idänpään-Heikkilä, J.J. et al. (1997) Journal of Pharmacology and Experimental Therapeutics 282 (3): 1366-1372. “Prevention of Tolerance to the Antinociceptive Effects of Systemic Morphine by a Selective Cholecystokinin-B Receptor Antagonist in a Rat Model of Peripheral Neuropathy.” [Juhana J. Idänpään-Heikkilä, Gisèle Guilbaud & Valérie Kayser] Jansen, Karl (2001) e-mail correspondence with Jon Hanna (Book reference is to Ketamine: Dreams & Realities by Karl Jansen; see www.maps.org) Kellstein, David E. & David J. Mayer (1990) Brain Research 516: 263-270. “Chronic administration of cholecystokinin antagonists reverses the enhancement of spinal morphine analgesia induced by acute pretreatment.” Ott, Jonathan (1999) Entheogen Review 7(2): 62-73. “Jonathan Ott Speaks…Part Two.” (Interviewed by Will Beifuss & Jon Hanna in 1998) (Proglumide comments are on p. 69) Pain Therapeutics, Inc., 250 E. Grand Avenue, STE 70, San Francisco, CA 94080 Peterson, F.J. et al. (1983) Gastroenterology 85(1): 122-129. “Prevention of acetaminophen and cocaine hepatotoxicity in mice by cimetidine treatment.” [F.J. Peterson, R.G. Knodell, N.J. Lindemann & N.M. Steele] [Abstract from PubMed] Pellinen, P. et al. (1994) Eur. J. Pharmacol. 270(1): 35-43. “Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors.” [P. Pellinen, P. Honkakoski, F. Stenback, M. Niemitz, E. Alhava, O. Pelkonen, M.A. Lang & M. Pasanen] [Abstract from PubMed] R.A.H. (2000) Entheogen Review 9(3): 145-147. “Opiate Potentiation.” Watkins, L.R. et al. (1984) Science 224: 395-396. “Potentiation of Opiate Analgesia and Apparent Reversal of Morphine Tolerance by Proglumide.” [L.R. Watkins, I.B. Kinscheck & D.J. Mayer] Xu, X.-J., et al. (1993) Neuroscience Letters 152: 129-132. “Up-regulation of cholecystokinin in primary sensory neurons is associated with morphine insensitivity in experimental neuropathic pain in the rat.” [X.-J. Xu, M.J.C. Puke, V.M.K. Verge, Z. Wiesenfeld-Hallin, J. Hughes & T. Hökfelt] Xu, X.-J., et al. (1994) Pain 56: 271-277. “Chronic pain-related behaviors in spinally injured rats: evidence for functional alterations of the endogenous cholecystokinin and opioid systems.” [Xiao-Jun Xu, Jing-Xia Hao, Åke Seiger, John Hughes, Tomas Hökfelt & Zsuzsanna Wiesenfeld-Hallin] Additional information that was not used or referenced above:

CCK activity as opioid antagonist (See also CCK inhibitor references below),
Faris, P.L. et al. (1983) Science 310-312. “Evidence for the neuropeptide cholecystokinin as an antagonist of opiate analgesia.” [P.L. Faris, B.R. Komisaruk, L.R. Watkins & D.J. Mayer]Itoh, S. et al. (1982) Eur. J. Pharmacol. 80: 421-425. “Caerulein and cholecystokinin suppress B-endorphin-induced analgesia in the rat.” [S. Itoh, G. Katsuura & Y. Maeda] Nichols, M.L. et al. (1995) J. Pharmacol. Exp. Ther. 275: 1339-1345. “Regulation of morphine anti allodynic efficacy by cholecystokinin in a model of neuropathic pain in rats.” [M.L. Nichols, D. Bian, M.H. Ossipov, J. Lai, & F. Porreca] Wiesenfeld-Hallin, Z. & X-J. Xu (1996) Regulatory Peptides 65: 23-28. “The role of cholecystokinin in nociception, neuropathic pain and opiate tolerance.”

CCK inhibitors enhancing opioid analgesia and/or preventing tolerance
Dourish, C.T. et al. (1988) Eur. J. Pharmacol. 147: 469-472. “Enhancement of morphine analgesia and prevention of morphine tolerance in the rat by the cholecystokinin antagonist L-364,718.” [C.T. Dourish, D. Hawley & S.D. Iversen]Dourish, C.T. et al. (1990) Eur. J. Pharmacol. 176: 35-44. “The selective CCK-B antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat.” [C.T. Dourish, M.F. O’Neill, J. Coughlan, S.J. Kitchener, D. Hawley & S.D. Iversen] Hoffmann, O. & Z. Wiesenfeld-Hallin (1994) Neuro. Report 5: 2565-2568. “The CCK-B receptor antagonist CI 988 reverses tolerance to morphine in rats.” Hughes, J. et al. (1990) Proceedings of the National Academy of Science (USA) 87: 6728-6732. “Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity.” [J. Hughes, P. Boden, B. Costall, A. Domeney, E. Kelly, D.C. Horwell, J.C. Hunter, R.D. Pinnock & G.N. Woodruff] O’Neill, M.F. et al. (1989) Neuropharmacology 28: 243-249. “Morphine-induced analgesia in the rat paw is blocked by CCK and enhanced by the CCK antagonist MK-329.” [M.F. O’Neill, C.T. Dourish & S.D. Iversen] Watkins, L.R. et al. (1985) Brain Research 327: 181-190. “Cholecystokinin antagonists selectively potentiate analgesia induced by endogenous opiates.” [L.R. Watkins, I.B. Kinscheck, E.F.S. Kaufman, J. Miller, H. Frenk & D.J. Mayer] Wiesenfeld, Z. et al. (1990) Proceedings of the National Academy of Science (USA) 87: 7105-7109. “PD134308, a selective antagonist of cholecystokinin type-B receptor, enhances the analgesic effect of morphine and synergistically interacts with intrathecal galanin to depress spinal nociceptive reflexes.” [Z. Wiesenfeld, X.-J. Xu, J. Hughes, D.C. Horwell & T. Hökfelt] Xu, X,-J. et al. (1992) British Journal of Pharmacology 105: 591-596. “CI988, a selective antagonist of cholecystokinin type-B receptor, prevents morphine tolerance in the rat.” [X.-J. Xu, Z. Wiesenfeld-Hallin, J. Hughes, D.C. Horwell & T. Hökfelt]

Grapefruit juice
Bailey, D.G. et al. (1998) British Journal of Clinical Pharmacology 46(2): 101-110. “Grapefruit juice-drug interactions.” [David G. Bailey, J. Malcolm, O. Arnold & J.David Spence]Edwards, D.J. et al. (1996) Drug Metab. Dispos. 24(12): 1287-1290. “Identification of 6′,7′-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice.” [D.J. Edwards, F.H. Bellevue III & P.M. Woster] [Abstract from PubMed] Fuhr, U. (1998) Drug Safety 18(4): 251-272. “Drug interactions with grapefruit juice. Extent, probable mechanism and clinical relevance.” [Abstract from PubMed] He, K. et al. (1998) Chem. Res. Toxicol. 11(4): 252-259. “Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice.” [K. He, K.R. Iyer, R.N. Hayes, M.W. Sinz, T.F. Woolf & P.F. Hollenberg] [Abstract from PubMed] Tirillini B. (2000) Fitoterapia 71: S29-S37. “Grapefruit: the last decade acquisitions.” [Abstract from PubMed]

Naloxone, naltrexone & nalmefene enhancing morphine analgesia and/or attenuating tolerance and dependence
Bergman, St.A. et al. (1988) Arch. Int. Pharmacodyn. 291: 229-237. “Low dose naloxone enhances buprenorphine in a tooth pulp antinociceptive assay.” (St.A. Bergman, R.L. Wynn, D.E. Myers & F.G. Rudo]Crain, S.M. & K.-F. Shen (1995a) Proceedings of the National Academy of Science (USA) 92: 10540-10544. “Ultra-low concentrations of naloxone selectively antagonize excitatory effects of morphine on sensory neurons, thereby increasing its antinociceptive potency and attenuating tolerance/dependence during chronic cotreatment.” Crain, S.M. & K.-F. Shen (1996) US Patent No. 5,512,578, US Patent Office. “Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by exogenous and endogenous opioid agonists.” Crain, S.M. & K.-F. Shen (1996) US Patent No. 5,580,876, US Patent Office. “Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by morphine and other bi-modally-acting opioid agonists.” Crain, S.M. & K.-F. Shen (1998b) Trends Pharmacol. Sci. 19: 358-365. “Modulation of opioid analgesia, tolerance and dependence by Gs-coupled, GM1 ganglioside-regulated opioid receptor functions.” Gan, T.J. et al. (1997) Anethesiology 87: 1075-1081. “Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate.” [T.J. Gan, B. Ginsberg, P.S.A. Glass, J. Fortney, R. Jhaveri & R. Perno] Gillman, M.A. & F.J. Lichtigfeld (1985) Neurol. Res. 7: 106-119. “A pharmacological overview of opioid mechanisms mediating analgesia and hyperalgesia.” (Review) Gillman, M.A. & F.J. Lichtigfeld (1989) Int. J. Neurosci. 48: 321-324. “Naloxone analgesia: an update.” (Review) Holmes, B.B. & J.M. Fujimoto (1993) Anesth. Analg. 77: 1166-1173. “Inhibiting a spinal dynorphin A component enhances intrathecal morphine antinociception in mice.” Joshi, G.P. et al. (1999) Anesthesiology 90: 1007-1011. “Effects of prophylactic nalmefene on the incidence of morphine-related side effects in patients receiving intravenous patient-controlled analgesia.” [G.P. Joshi, J. Duffy, J. Chehade, J. Wesevich, N. Gajraj & E.R. Johnson] Levine, J.D. et al. (1988) J. Clin. Invest. 82: 1574-1577. “Potentiation of pentazocine analgesia by low-dose naloxone.” [J.D. Levine, N.C. Gordon, Y.O. Taiwo & T.J. Coderre] Shen, K.-F. & S.M. Crain (1997) Brain Research 757: 176-190. “Ultra-low doses of naltrexone or etorphine increase morphine’s antinociceptive potency and attenuate tolerance/dependence in mice.”

Proglumide
Chiodo, L.A. & B.S. Bunney (1983) Science 219: 1449-1450. “Proglumide, selective antagonism of excitatory effect of cholecystokinin in central nervous system.”Katsuura, G. & S. Itoh (1985) Eur. J. Pharmacol. 107: 363-366. “Potentiation of ß-endorphin effects by proglumide in the rat.” Lavigne, G. et al. (1987) Pain, Suppl. 4: S229. “Potentiation of morphine analgesia by proglumide for acute clinical pain.” [G. Lavigne, K.M. Hargreaves, G.P. Miller, E.S. Schmidt & R.A. Dionne] McCleane, G.J. (1998) Anesth. Anal. 87: 1117-1120. “The cholecystokinin antagonist proglumide enhances the analgesic efficacy of morphine in humans with chronic benign pain.” McCleane, G.J. (1998) The Pain Clinic 11: 103-107. “The cholecystokinin antagonist proglumide enhances the analgesic effect of morphine in chronic benign nociceptive and neuropathic pain.” Rovati, L.C. et al. (1985) Annals of the New York Academy of Science 448: 630-632. “Effects of proglumide on morphine analgesia and tolerance.” [L.C. Rovati, P. Sacerdote & A.E. Panerai] Tang, J. et al. (1984) Neuropharmacology 23 (6): 715-718. “Proglumide prevents and curtails acute tolerance to morphine in rats.” [J. Tang, J. Chou, M. Iadarola, H.-Y.T. Yang & E. Costa] Watkins, L.R. et al. (1985) Brain Research 327: 169-180. “Potentiation of morphine analgesia by the cholecystokinin antagonist proglumide.” [L.R. Watkins, I.B. Kinscheck & D.J. Mayer]

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