Preventing or Reducing Tolerance - Must Be A Way

[I-Nod]

I've been reading and researching for the past week, finding every way possible to potentiate my opiates so they are stronger and last longer.

Earlier I came across this article on Erowid about Hydroxyzine being able to prevent further tolerance, and quite possibly reducing it! First off, I never even thought this was possible. Now I'm more interested than ever to find a way to reduce my tolerance (w/ out quitting!), or at least prevent it from increasing further.

I wanted to open this thread for any discussion or articles you may have run across, that's geared towards reduction or prevention of opiate tolerance. With so much emphasis on potentiating or using different ROA's to achieve better highs, or make our stash last longer, it only makes sense that this subject at hand would prove way more valuable if in fact it's possible to achieve.

I've found a couple articles already, I'll post the one here now and get the other up shortly. http://www.erowid.org/chemicals/opiates/opiates_info3.shtml
I apologize if this has already been posted, too. I just figured if we put our collective junky-minds together, we could possibly figure this shit out! I mean, hell, we tend to get through every "abuse" preventative devices they throw at us... and these pharmaceutical companies spend millions and millions on their research, only to have some "worthless, degenerates" crack the code in no time flat. Except now, our opponent is mother nature herself... which won't be nearly as easy, but I have faith in the genius on this board! :D Please post any info or experiences you may have here, much appreciation!!

[pharmboy]

I have tried Vistiral / Hydroxyzine , no big woop. Maybe a little more

of a nod. And it is a antihistamine.

[pharmboy]

The low dose Naltrexone thing sounds promising.

But I hate even the word Naltrexone.

But neuropharmacologically it might work.

[doctor diesel]

What about that proglumide stuff?
That was meant to show promise, wasn't it, way back when it was being discussed on this forum?


Doc

[I-Nod]

I have tried Vistiral / Hydroxyzine , no big woop. Maybe a little more

of a nod. And it is a antihistamine.

Did you happen to try it for an extended period of time? I'm not sure but I was thinking that perhaps using it for a bit you may notice that your tolerance isn't going up any longer. I'm just diving into this shit though, I know nothing about it. Just was hoping I could find a way to stay at my current dose for years and years and still get a nod on... or even better, be able to decrease my dose and nod.


The low dose Naltrexone thing sounds promising.

But I hate even the word Naltrexone.

But neuropharmacologically it might work.

I think the Naltrexone would only help at keeping your tolerance the same, indefinitely. I guess the idea is to take very miniscule amounts. The N is supposedly used to rip the opiates off the receptors so more can reattach, allowing you to feel pretty high w/out your brain naturally making more receptors. I'm horrible at explaining, but I'd just read the description and it was worded much better.

What about that proglumide stuff?
That was meant to show promise, wasn't it, way back when it was being discussed on this forum?


Doc

I just got done reading it, and indeed it was promising. Have you tried it Doc? I think they took it off the market here in the states... pretty sure I read that they do still have it (whatever the main ingredient is, it goes by a different name) in the UK, though.

What's funny is, some of these things aren't expensive at all, and OTC... hope somebody has tried one of them out at some time. I'm definitely going to as soon as I get paid! I'll report back if I notice anything. Of course it will take months, as my tolerance doesn't build all that quickly. Thank you kindly Pharmboy and Doctor Diesel!! Guess I got a little too excited over this, it's old news. Hope somebody gave it one hell of a trial though :D

[doctor diesel]

Hey Nod,

No I never tried the proglumide, but I was so fascinated at the promise it held, that I ordered some of the stuff on the internet, paying £60 ($120) for it.
And guess what: it never came.
That was the beginning, middle and end of my scientific experimentation.


Doc

[wafflehead77]

What abou dextromethorphan (dxm)? doesnt it show promine in stopping and lowering tolerance to several classes of psychoactives?

[edhorfin]

Countless hours spent pondering the same problem, really the ONLY problem with opiates- I've read plenty about proglumide and would really love to try it, but I can't find it anywhere.

Has anyone here ever tried it? (I also didnt UTFSE, sorry)

Jacky???

[NastyZilla]

I have been trying like crazy to get my hands on some proglumide, to no avail. Sure, you can buy the raw shit from China (not too happy about that idea - China has had NO luck with quality control lately!), but I want the proglumide in pill form, with a measurable weight (apx. 250mg per pill is standard, I think).

Pisses me off! If you search sciencedirect.com and other sources for scientific articles there have been recent research articles about the success of using proglumide to fight addictive behaviors as well.. . for instance, I recently printed off a synopsis of a study that found proglumide could be used to reduce gambling behavior! In other words, proglumide may impact complusive, addictive behaviors... hell, that would be PERFECT... proglumide can increase the impact of your DOC (decrease tolerance) while hopefully making it less likely that you will even want to do your DOC!

Now if only someone would import some of that shit, press it into (safe) pills, and sell it to us as a dietary supplement (which are subject to very little FDA oversight)...

HEY VENDORS - ANYONE READING THIS!? SELL PROGLUMIDE on the 'Net!

[I-Nod]

Hey Nod,

No I never tried the proglumide, but I was so fascinated at the promise it held, that I ordered some of the stuff on the internet, paying £60 ($120) for it.
And guess what: it never came.
That was the beginning, middle and end of my scientific experimentation.


Doc

Ouch!! That's a bunch of horse shit Dr Diesel!!... I could understand if it was some junky who "will be right back, wait here... dude gets sketched out", but to charge that much for $10 worth of product and not even deliver it??? Sorry to hear, man. I'm sure that solidified your faith in the human race :rolleyes:

What abou dextromethorphan (dxm)? doesnt it show promine in stopping and lowering tolerance to several classes of psychoactives?

Not sure about that one, wafflehead. Had to get my internet restored, out since last night, so I haven't read up on anything new.

On that note... I was very proud of Ophile after I searched Proglumide here... there are quite a few threads on this very subject. I apologize to everybody for creating a duplicate thread... put the tar & feathers away, please. :o I must've been under a rock for a while there. Perhaps this can be an experimental thread. I'll definitely experiment w/ any substances that show promise and are reasonably available. No sense in testing something that is damn near impossible to get ahold of. Ashwanganda sounds very promising but I believe I read (it was yrs ago so I very well could be wrong) it is illegal in the US.

I have been trying like crazy to get my hands on some proglumide, to no avail. Sure, you can buy the raw shit from China (not too happy about that idea - China has had NO luck with quality control lately!), but I want the proglumide in pill form, with a measurable weight (apx. 250mg per pill is standard, I think).

Pisses me off! If you search sciencedirect.com and other sources for scientific articles there have been recent research articles about the success of using proglumide to fight addictive behaviors as well.. . for instance, I recently printed off a synopsis of a study that found proglumide could be used to reduce gambling behavior! In other words, proglumide may impact complusive, addictive behaviors... hell, that would be PERFECT... proglumide can increase the impact of your DOC (decrease tolerance) while hopefully making it less likely that you will even want to do your DOC!

Now if only someone would import some of that shit, press it into (safe) pills, and sell it to us as a dietary supplement (which are subject to very little FDA oversight)...

HEY VENDORS - ANYONE READING THIS!? SELL PROGLUMIDE on the 'Net!

Wow, that's a big bummer! If there's anything I'm certain of about you, it's that you are a determined and focused woman... so if you're having a hard time finding it, I'm S.O.L.

The funny thing is, the one site I read about it at was saying that Proglumide worked very well as it was originally intended for. Can't remember why they pulled it, but it was something stupid, think I read it on Wiki.

Lastly Edhorfin, it doesn't look too promising. I'm sure that some ROP sells it somewhere out there, but if the prices are like Doctor Diesel's findings (or lack of), it almost wouldn't be worth it. Perhaps whatever the main ingredient is, is in something else? I'll have to look into that... what I'd give to half my tolerance!!!! Much thanks everyone!! Again, sorry to start a thread that is extensively covered already :o:o

[EleusisII]

Just read this on another board. Might be worth a try...

My doctor gave me Theramine, a medical food. Sounds like it works like Proglumide and the doctor explained it should help tolerance reduction. I'm suppose to take 2-capsules every 4 hours, I haven't noticed any difference at all. Just thought I would share my info.

[pharmboy]

I tried the Visteral for about a month, after about a week it stoped
potentiating, I dont know about tolerance.

I have never tried Low dose Naltrexone.

I hope find the cure Nod.

[NastyZilla]

I recently printed off a synopsis of a study that found proglumide could be used to reduce gambling behavior! In other words, proglumide may impact complusive, addictive behaviors... hell, that would be PERFECT... proglumide can increase the impact of your DOC (decrease tolerance) while hopefully making it less likely that you will even want to do your DOC!



I'M WRONG, GUYS! It wasn't proglumide, but N-Acetyl Cysteine I was thinking about. So I'm not a chemist... sue me.:D

The chemical that may assist in reducing the compulsive desires that help cause pathological gambling is N-Acetyl Cysteine, or NAC.

NAC is available from drugstore.com without a prescription, thank God.

Here's the synopsis of the Study, performed in 2006:
"An Open Label Study of N-Acetyl Cysteine in Pathological Gambling"
Sponsored by the University of Minnesota, January 2006
ClinicalTrials.gov identifier: NCT00273702

Purpose: Subjects were raised over a few weeks from 600mg a day to 1800mg a day (unless clinical improvement was obtained at a lower level) in an attempt to reduce their obsessive/compulsive behaviors.

If you search www.sciencedirect.com (http://www.sciencedirect.com) for "n-acetyl cysteine" you'll find the following article that was written concerning the outcome of the trial cited above:

"N-Acetyl Cysteine, a Glutamate-Modulating Agent, in the Treatment of Pathological Gambling: A Pilot Study" by Jon E. Grant, Suck Won Kim and Brian L. Odlaug
Department of Psychiatry University of Minnesota School of Medicine,
published in Biological Psychiatry, Volume 62, Issue 6, 15 September 2007, Pages 652-657.
Background

Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. N-acetyl cysteine (NAC), an amino acid, seems to restore extracellular glutamate concentration in the nucleus accumbens and therefore offers promise in reducing addictive behavior.
Methods
Twenty-seven subjects (12 women) with DSM-IV PG were treated in an 8-week open-label trial of NAC with responders (defined as a ≥ 30% reduction in Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling [PG-YBOCS] total score at end point) randomized to 6 weeks of double-blind NAC or placebo.
Results
The PG-YBOCS scores decreased from a mean of 20.3 ± 4.1 at baseline to 11.8 ± 9.8 at the end of the open-label phase (p < .001). Sixteen of 27 subjects (59.3%) met responder criteria. The mean effective dose of NAC was 1476.9 ± 311.3 mg/day. Of 16 responders, 13 entered the double-blind phase. Of those assigned to NAC, 83.3% still met responder criteria at the end of the double-blind phase, compared with only 28.6% of those assigned to placebo.
Conclusions The efficacy of NAC lends support to the hypothesis that pharmacological manipulation of the glutamate system might target core symptoms of reward-seeking addictive behaviors such as gambling. Larger, longer, placebo-controlled double-blind studies are warranted."

I also found two other articles mentioned on the 'net, but I have not checked primary reference materials to ensure these cites are correct:

1. Is cocaine desire reduced by N-acetylcysteine?, Am J Psychiatry. 2007 Jul;164(7):1115-7. LaRowe SD, Myrick H, Hedden S, Mardikian P, Saladin M, McRae A, Brady K, Kalivas PW, Malcolm R. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC.
The study: In this double-blind, placebo-controlled trial, 15 volunteers received acetylcysteine or placebo during a 3-day hospitalization. Participants were crossed over to receive the opposite condition on a second, identical 3-day stay occurring 4 days later. During each hospital stay, participants completed a cue-reactivity procedure that involved collecting psychophysical and subjective data in response to slides depicting cocaine and cocaine use. While taking N-acetylcysteine, participants reported less desire to use and less interest in response to cocaine slides and watched cocaine slides for less time.

and

2. An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study, Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):389-94. Mardikian PN, LaRowe SD, Hedden S, Kalivas PW, Malcolm RJ. Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President Street, Charleston, SC 29425, USA.
The Study: Twenty three treatment-seeking cocaine-dependent patients participated in a 4-week medication trial and received N-acetylcysteine at doses of 1200 mg/day, 2400 mg/day or 3600 mg/day. Results suggested that the three doses were well tolerated. Overall, the retention rates appeared to favor higher doses of NAC (2400 mg/day and 3600 mg/day). The majority of subjects who completed the study either terminated use of cocaine completely or significantly reduced their use of cocaine during treatment.


Here are my questions to the Board:
There are people on this forum who are taking NAC for its ability to reduce liver toxicity of tylenol (NAC is an antidote of sorts for tylenol poisoning because it helps the liver produce glutathione since NAC is a precursor of glutathione and increases its availability).

1. Has anyone noticed any reduced mental desire to take their DOC?

2. Is it worth trying NAC at the study's recommended levels, perhaps in conjunction with proglumide, in an attempt to reduce tolerance and dependence?

Sorry for the lenthy post.
Due to the potential interest in this idea, I will post this info in a new thread, however, I didn't want to leave my prior post uncorrected since it was very wrong.

[EleusisII]

I've taken NAC to ward off the evil Tylenol, about a gram a day.
I wouldn't be able to tell ya. I'll keep my eye out for that effect though :)

[edhorfin]

I'M WRONG, GUYS! It wasn't proglumide, but N-Acetyl Cysteine I was thinking about. So I'm not a chemist... sue me.:D

The chemical that may assist in reducing the compulsive desires that help cause pathological gambling is N-Acetyl Cysteine, or NAC.

NAC is available from drugstore.com without a prescription, thank God.

Here's the synopsis of the Study, performed in 2006:
"An Open Label Study of N-Acetyl Cysteine in Pathological Gambling"
Sponsored by the University of Minnesota, January 2006
ClinicalTrials.gov identifier: NCT00273702

Purpose: Subjects were raised over a few weeks from 600mg a day to 1800mg a day (unless clinical improvement was obtained at a lower level) in an attempt to reduce their obsessive/compulsive behaviors.

If you search www.sciencedirect.com (http://www.sciencedirect.com) for "n-acetyl cysteine" you'll find the following article that was written concerning the outcome of the trial cited above:

"N-Acetyl Cysteine, a Glutamate-Modulating Agent, in the Treatment of Pathological Gambling: A Pilot Study" by Jon E. Grant, Suck Won Kim and Brian L. Odlaug
Department of Psychiatry University of Minnesota School of Medicine,
published in Biological Psychiatry, Volume 62, Issue 6, 15 September 2007, Pages 652-657.
Background

Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. N-acetyl cysteine (NAC), an amino acid, seems to restore extracellular glutamate concentration in the nucleus accumbens and therefore offers promise in reducing addictive behavior.
Methods
Twenty-seven subjects (12 women) with DSM-IV PG were treated in an 8-week open-label trial of NAC with responders (defined as a ≥ 30% reduction in Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling [PG-YBOCS] total score at end point) randomized to 6 weeks of double-blind NAC or placebo.
Results
The PG-YBOCS scores decreased from a mean of 20.3 ± 4.1 at baseline to 11.8 ± 9.8 at the end of the open-label phase (p < .001). Sixteen of 27 subjects (59.3%) met responder criteria. The mean effective dose of NAC was 1476.9 ± 311.3 mg/day. Of 16 responders, 13 entered the double-blind phase. Of those assigned to NAC, 83.3% still met responder criteria at the end of the double-blind phase, compared with only 28.6% of those assigned to placebo.
Conclusions The efficacy of NAC lends support to the hypothesis that pharmacological manipulation of the glutamate system might target core symptoms of reward-seeking addictive behaviors such as gambling. Larger, longer, placebo-controlled double-blind studies are warranted."

I also found two other articles mentioned on the 'net, but I have not checked primary reference materials to ensure these cites are correct:

1. Is cocaine desire reduced by N-acetylcysteine?, Am J Psychiatry. 2007 Jul;164(7):1115-7. LaRowe SD, Myrick H, Hedden S, Mardikian P, Saladin M, McRae A, Brady K, Kalivas PW, Malcolm R. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC.
The study: In this double-blind, placebo-controlled trial, 15 volunteers received acetylcysteine or placebo during a 3-day hospitalization. Participants were crossed over to receive the opposite condition on a second, identical 3-day stay occurring 4 days later. During each hospital stay, participants completed a cue-reactivity procedure that involved collecting psychophysical and subjective data in response to slides depicting cocaine and cocaine use. While taking N-acetylcysteine, participants reported less desire to use and less interest in response to cocaine slides and watched cocaine slides for less time.

and

2. An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study, Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):389-94. Mardikian PN, LaRowe SD, Hedden S, Kalivas PW, Malcolm RJ. Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President Street, Charleston, SC 29425, USA.
The Study: Twenty three treatment-seeking cocaine-dependent patients participated in a 4-week medication trial and received N-acetylcysteine at doses of 1200 mg/day, 2400 mg/day or 3600 mg/day. Results suggested that the three doses were well tolerated. Overall, the retention rates appeared to favor higher doses of NAC (2400 mg/day and 3600 mg/day). The majority of subjects who completed the study either terminated use of cocaine completely or significantly reduced their use of cocaine during treatment.


Here are my questions to the Board:
There are people on this forum who are taking NAC for its ability to reduce liver toxicity of tylenol (NAC is an antidote of sorts for tylenol poisoning because it helps the liver produce glutathione since NAC is a precursor of glutathione and increases its availability).

1. Has anyone noticed any reduced mental desire to take their DOC?

2. Is it worth trying NAC at the study's recommended levels, perhaps in conjunction with proglumide, in an attempt to reduce tolerance and dependence?

Sorry for the lenthy post.
Due to the potential interest in this idea, I will post this info in a new thread, however, I didn't want to leave my prior post uncorrected since it was very wrong.


I've take NAC every day because hep c has shafted my liver. It hasn't affected my desire to take my DOC or any other D either. Its worth trying the proglumide alone, without the NAC to see if IT works, and then maybe try it in conjuntion with the NAC. BTW, the doses of NAC used for APAP poisoning are very high and IV. Someone close to me tried to OD using an APAP bsed OTC drug and was given IV NAC for several days in the ICU. It works wonders for APAP poisoning, a real lifesaver...

[Z-man]

Found a couple of recent articles on the subject of eliminating tolerance:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2045628
http://healthfinder.gov/news/newsstory.asp?Docid=609660

I don't believe I've seen anything about this particular approach mentioned here before. Anyone think it might really amount to anything?

[hydrocodonious]

The article you posted is a commentary to this article which is a little more clear on the subject.
I was wondering why the first article i read never gave the formula for the peroxynitrite ion (ONOO-), and why the title was rather unscientific haha.


Therapeutic manipulation of peroxynitrite attenuates the development of opiate-induced antinociceptive tolerance in mice
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2045607

Here is the abstract if you dont want to read the article:

"Severe pain syndromes reduce quality of life in patients with inflammatory and neoplastic diseases, often because chronic opiate therapy results in reduced analgesic effectiveness, or tolerance, leading to escalating doses and distressing side effects. The mechanisms leading to tolerance are poorly understood. Our studies revealed that development of antinociceptive tolerance to repeated doses of morphine in mice was consistently associated with the appearance of several tyrosine-nitrated proteins in the dorsal horn of the spinal cord, including the mitochondrial isoform of superoxide (O2–) dismutase, the glutamate transporter GLT-1, and the enzyme glutamine synthase. Furthermore, antinociceptive tolerance was associated with increased formation of several proinflammatory cytokines, oxidative DNA damage, and activation of the nuclear factor poly(ADP-ribose) polymerase. Inhibition of NO synthesis or removal of O2– blocked these biochemical changes and inhibited the development of tolerance, pointing to peroxynitrite (ONOO–), the product of the interaction between O2– and NO, as a signaling mediator in this setting. Indeed, coadministration of morphine with the ONOO– decomposition catalyst, Fe(III) 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin, blocked protein nitration, attenuated the observed biochemical changes, and prevented the development of tolerance in a dose-dependent manner. Collectively, these data suggest a causal role for ONOO– in pathways culminating in antinociceptive tolerance to opiates. Peroxynitrite (ONOO–) decomposition catalysts may have therapeutic potential as adjuncts to opiates in relieving suffering from chronic pain."

[Hammilton]

glutethimide- ftw

[morphiquet]

why not use the newer lorglumide instead of proglumide? it's also a cck-antagonist and is still prescribed today.