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Thread: Methadone's G-Spot

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    Methadone's G-Spot 
    #1
    Since Valentine4's thread was closed, I wanted to create a thread to continue one of the discussions.

    Popular junkie lore and media sensationalism have pushed certain ideas of Methadone potentiation. The feds are concerned about people taking herbal supplements, acid reflux medication and anti-depressants with Methadone to increase the high, the media jumps all over reports of Methadone clinic patients and recreational drug users stealing Prilosec to boost their Methadone, and the death of Anna Nicole Smith's son from a combination of anti-Depressants and Methadone.

    So, according to numerous sources, Methadone is metabolised by the Cytochrome P450 group of enzymes.

    CYP450 Enzymes Metabolizing Methadone

    CYP3A4: Important methadone metabolizer (can also be induced by methadone during the early start-up phase of MMT).

    CYP2B6: Relatively recently discovered as an important methadone metabolizer.

    CYP2D6: Secondary role (methadone can inhibit this enzyme in same cases and this enzyme is particularly involved in the metabolism of active R-methadone).

    CYP1A2: Possibly involved (clinical significance still under investigation).
    So we know for certain that three Cytochrome P450 enzymes are involved in the metabolism of Methadone, with the possibility of more being involved (Note: Previously CYP2C9 and 2C19 were thought to be involved, but this has not been confirmed (Crettol et al. 2005).").

    CYP3A4 is listed in many places as the 'most important' enzyme involved in the metabolism of Methadone.

    Cytochrome P450 3A4 (abbreviated CYP3A4), a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. CYP3A4 is also, correspondingly, present in the largest quantity of all the CYPs in the liver.
    Also

    A substrate is any drug metabolized by one or more CYP enzymes, and more than half of all
    medications that undergo metabolism are CYP3A4 substrates (Piscitelli and Rodvold, 2001).
    And

    CYP3A4, the most abundant metabolic enzyme in the body, can vary 30-fold between individuals
    in terms of its presence and activity in the liver (Eap et al. 2002; Leavitt et al. 2000). This enzyme also
    is found in the gastrointestinal tract, so methadone metabolism actually can begin before the drug
    enters the circulatory system (Hardman et al. 1996). The amount of this enzyme in the intestine can
    vary up to 11-fold, partially accounting for some individual differences in the breakdown and
    absorption of methadone (Levy et al. 2000).
    So, while CYP3A4 is very important in the metabolism of Methadone, it is found in very high numbers compared to other CYP450 enzymes, which means that the maximum potentiation of subjective physiological effects from inhibiting CYP3A4 will be less than that of a less prevalent enzyme.

    The other important enzyme in the metabolism of Methadone is CYP2B6. This enzyme is much less prevalent than CYP3A4. In fact,
    "CYP2D6 is entirely absent in a significant portion of the population (1 out of 15 persons), resulting in
    increased sensitivity to methadone’s effects; conversely, some persons have high activity of this
    enzyme and are rapid metabolizers of methadone (Eap et al. 2002)."


    The impact and importance of this enzyme in Methadone metabolism is a recent discovery, and there are not many known inducers and inhibitors of CYP2B6 (compared to other known enzymes). Interestingly, there is one particular known strong inhibitor of CYP2B6, which is my main focus in creating this thread: Orphenadrine.

    Orphenadrine (Brand name Norflex) is an anti-cholinergic/anti-muscarinic of the ethanolamine antihistamine class that is related to Diphenhydramine. It has a number of clinical uses, and on its own has many interesting attributes.

    Euphoria is an effect reported by many patients and orphenadrine has been investigated for use against depression, as first reported in June 1958 in the American Journal of Psychiatry (Am J Psychiatry 114:1113–1115, June 195

    . . .

    Orphenadrine exerts its effects both peripherally and in the central nervous system (CNS). In this latter respect, is similar to the chemically-unrelated drug nefopam as being a centrally-acting but non-opioid analgesic. Rather than binding to receptors as do opioids, benzodiazepines, seritonergic stimulants and the like, the central effect is the result of a change in the dopamine:acetylcholine ratio in the CNS because like other anticholinergics, it modifies dopamine and acetylcholine levels. Orphenadrine can also have a more comprehensive effect in both acute and chronic pain -- i.e. working against suffering -- in that the same effect also produce slight to moderate euphoria that lasts many hours and which is, for the above-given reasons, not the potential basis of addiction and abuse. Another reason for this drug's lack of habituation potential would be that the result of repeated supertherapeutic doses and/or significantly shortened dosage intervals is unpleasant, producing side effects much like those of atropine.

    . . .

    Patients given hydromorphone and orphenadrine simultaneously report increased efficacy and duration of action of both agents, reduction of nausea, insomnia, and boosted euphoria to a level greater than the sum of its parts. The itching notable with codeine, dihydrocodeine, morphine and the like are also lessened or eliminated.

    . . .

    Last but not least, orphenadrine may have yet another effect with respect to opioids: a clonidine-like effect on withdrawal symptoms useful for abrupt "cold turkey" cessation or accelerated tapers. Other NMDA receptor antagonists have been demonstrated to have weakened opioid withdrawal syndromes.[2] Clonidine is another drug that has these effects, although usually much stronger that orphenadrine.
    The note specifically on combining Orphenadrine with Hydromorphone is very interesting, as it gives a good indication of what can be expected from a combination of Opioids and Orphenadrine in general.

    As a strong CYP2B6 Inhibitor, Orphenadrine should potentiate the subjective physiological effects of Methadone more than a CYP3A4 Inhibitor and/or CYP2D6 Inhibitor (Cimetidine, GFJ, Goldenseal, Cat's Claw, Ranitidine, etc) or a competing substrate (Omeprazole [Prilosec]).

    But, since strong CYP2B6 Inhibition is not the only mechanism that Orphenadrine effects the subjective effects of Methadone, it is not a stretch to assume the combined impact of Orphenadrine on the metabolism and subjective effects of Methadone would be one of potentiation.

    Note: I do not endorse anyone consume any of the substances mentioned in this post. Specifically, taking a CYP2B6 Inhibitor with Methadone could very likely lead to coma or death, as the respiritory depression of Methadone would be greatly enhanced, which could likely cause a non-lethal dose of Methadone to become a highly lethal dose of Methadone. Since enzyme levels are so variable, and 1 in 15 people is estimated to not have any CYP2B6 enzyme at all, it would be very dangerous to put this into practice. Oversedation and respitory depression kills thousands of people every year- almost always this is the result of combining substances with a strong Opioid, and Methadone is notorious for causing death in people who recklessly consume it in high or regular doses, and especially when combined with other substances to enhance it.

    So, do not under any circumstances try anything in this post. This is for educational and debate purposes only!
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    #2
    Bluelight Crew fastandbulbous's Avatar
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    Lets not let this thread decend into bickering, OK people?

    PS I've had orphenadrine on it's own an it is indeed quite enjoyable (got it for whiplash after a minor car accident years ago). Wish I'd known about it's potentiation of opiates back then
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    #3
    I agree that the combination 'orphenadrine + methadone' is indeed potentially dangerous. Do we have any information about the duration of CYP2B6-inhibition by this compound?

    Murphy
    Last edited by MurphyClox; 28-10-2008 at 18:50.
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    #4
    Quote Originally Posted by MurphyClox
    I agree that the combination 'orphenadrine + methadone' is indeed potentially dangerous. Do we have any information about the duration of CYP2B6-inhibition by this compound?

    Murphy
    Orphenadrine's half-life is 13-20 hours after a single dose, 2 to 3 times longer with repeated administration over time:

    http://www.ncbi.nlm.nih.gov/sites/en...&dopt=Abstract

    I found this a second ago, seems very interesting in relation to this topic:

    Inhibition experiments
    The effect of selective inhibitors on the rate of artemisinin disappearance was investigated in microsomes pooled from 10 livers (Human Biologics International, Scottsdale, Arizona, USA). The selective inhibitors 8-methoxypsoralen (500 μm), orphenadrine (500 μm), ketoconazole (4 μm) and troleandomycin (50 μm) were used to investigate the involvement of CYP2A6 [12], CYP2B6 [13, 14], CYP3A4 [15, 16] and CYP3A4 [17], respectively. The effect of orphenadrine in combination with ketoconazole or 8-methoxypsoralen was investigated in these microsomes as well.
    Inhibition studies were also performed with characterized microsomes. Microsomes (Human Biologics International, Scottsdale, Arizona, USA) from one human liver (HBI 102) with high S-mephenytoin N-demethylation (CYP2B6) and dextromethorphan N-demethylation (CYP3A4) activity and microsomes from one liver (HBI 103) with low CYP2B6 and CYP3A4 activity were incubated with artemisinin in the presence of the CYP2B6 inhibitor orphenadrine (500 μm). The effect of the CYP3A4 inhibitor ketoconazole (4 μm) was also investigated in these two livers. In addition, artemisinin was coincubated with the antimalarial R,S-mefloquine (200 μm).

    The inhibitors were dissolved in dimethylsulphoxide (DMSO) (final concentration <0.5. The total incubation volume was 1 ml and the incubation was maintained at 37° C in a shaking water-bath. The reaction was initiated by addition of ice-cold NADPH after 2 min preincubation (10 min preincubation with troleandomycin) and the metabolic activity was terminated by addition of ice-cold MeOH (200 μl) to 100 μl sample at 0, 10, 20, 30 and 40 min. After centrifugation at 10 000 g for 10 min, 60 μl of the supernatant was injected directly onto the h.p.l.c. column. Control experiments were performed in parallel with artemisinin incubated without inhibitor but with 0.5% DMSO. All inhibition incubations were performed in triplicate.

    In addition, the specificity of orphenadrine, ketoconazole and 8-methoxypsoralen in inhibiting artemisinin metabolism was investigated in triplicate in microsomes from human B-lymphoblastoid cell lines expressing CYP2B6, CYP3A4 and CYP2A4, respectively.

    . . .

    Data analysis
    In incubations with microsomes from human lymphoblastoid cell lines expressing different isoenzymes, artemisinin disappearance rates (nmol min−1 mg−1 protein), adjusted for native activity were calculated. In incubations with characterized microsomes and pooled microsomes, artemisinin first-order elimination rate constants were estimated by log-linear regression of drug concentration–time data. The inhibition of artemisinin metabolism by the specific inhibitors was evaluated by comparing the first-order elimination rate constants (k) in the presence and absence of inhibitors [% inhibition=100×(kabsence-kpresence)/ kabscence].
    To compare artemisinin disappearance rates and specific CYP450 activities in characterized human liver microsomes, regression analysis was performed on log-transformed data for both dependent and independent variables due to skew distribution and in particular microsomes from one donor exhibiting generally very high enzyme activities and artemisinin disappearance rates. Since simple linear regressions of artemisinin metabolism rates against individual, specific enzyme activities in microsomes from different livers do not apply when enzyme activities correlate (coregulation), analysis by multiple regressions was initially considered for investigating the relative contribution of individual isoenzymes to the disappearance of artemisinin in characterized liver microsomes. After both forward and backward stepwise multiple regression, CYP2B6 activity was selected as explaining most of the variability in artemisinin disappearance rates, whereas the inclusion of other enzymes into the regression model was inconsistent (results not shown). The relationship between log artemisinin disappearance rate constants and log S-mephenytoin N-demethylation activities (CYP2B6 activity) (slope=0.97±0.04 (s.e.mean),r2=0.94) obtained from a simple regression analysis (Statistica, StatSoft, Tulsa, Okla) was by visual inspection of the plot not completely linear. Due to possible nonlinearities and subgroups with different contributions of individual isoenzymes, a tree-based model [19] was therefore chosen for the final regression analysis using Xpose 2.0 software [20]. This is further considered in the discussion section. Results are presented as median (range).

    . . .

    Results

    Incubations with cDNA-expressed human CYP450 isoenzymes
    In incubations with microsomes from the AHH-1 TK+/−human lymphoblastoid cell line, the most rapid disappearance of artemisinin, about 6 nmol min−1 mg−1 protein, was observed in microsomes expressing CYP2B6 (Figure 2). The rate of artemisinin metabolism was 7-fold and 10-fold higher in microsomes with cDNA-expressed CYP2B6 compared to cDNA-expressed CYP2A6 and CYP3A4, respectively. Low disappearance rates were seen in incubations with recombinant CYP1A1 and oxidoreductase. No or negligible disappearance of artemisinin was found with microsomes expressing CYP1A2, 2C19, 2C8, 2C9, 2D6, 2E1 and epoxide hydrolase. There was no difference in the relative order of the velocities between the different cDNA expressed enzymes in incubations with 1.0 mg ml−1 microsomal protein compared with 2.5 mg ml−1 protein, with the exception of CYP2E1 where the rate of artemisinin disappearance (mg−1 protein) was more rapid when incubated with 2.5 mg ml−1 compared with 1.0 mg ml−1 protein.
    http://www.pubmedcentral.nih.gov/art...?artid=2014388

    So Orphenadrine was used in this study to inhibit CYP2B6 to determine the impact of this enzyme inhibition on the metabolism of the malaria drug Artemisinin. The results make it sound like Orphenadrine acts specifically as a very strong CYP2B6 Inhibitor resulting in much higher concentrations of a CYP450 substrate (in this example Artemisinin, in my ex. Methadone) than if that drug were taken by itself without a CYP2B6 Inhibitor.

    Looks like some great evidence that my (albeit unoriginal) thesis is correct; that a strong CYP2B6 Inhibitor taken with Methadone should provide stronger subjective physiological effects than if the Methadone were taken alone or if it were taken with a CYP3A4 and/or CYP2D6 Inhibitor(s).
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    #5
    Bluelighter rachamim's Avatar
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    First, sad to see the other thread closed but it was expected. When people worry about the poster and not the infromation, and then criticise a poster instead of the information presentedby the poster, threads SHOULD be closed.

    That said, have to respond to one post in that closed thread and I believe it was by Limpet. Limpet, if it was he, said he believed I might have been arrogant in commenting that the majority of BLers could not understand something. Sorry, burt BL is a Harm Reduction site, not a synthesis site and certainly not a chemsitry site. When this forum was iniated, after about a month or so of lobbying, the powers that be warned that it would probably provide alot of infromation that would be unfathomable to most BLers.


    This not only has to do with the scope of the site, but in the overwhelming age of our members. If anyone cares to look into it they will find that most of our members are very young. Even if I had not been Israeli (we as a rule do not begin university until at least age 21 but almost always at age 22 or 23), had you asked me to chime in when I was like the majority of BLers (in terms of age), I would not had the slightest clue.

    Age does not equal education but it is a very good indicator. Neither is education neccessary to understand what was said but again, it is a good indicator. So, what I said was indeed the truth. It is not about pedestals, or arrogance, but rather a factual statement in terms of replying to the statement that "100 BLers" say "methadone is euphoric."


    The third thing is that I again need to spologise for my spelling. As some know, English is far from my favorite language. I almost always proofread my posts 2 or 3 times and edit when needed, but reviweing that thread just before I was taken aback at the number of spelling errors and will try to do better. I blame others for not understanding what I am expressing when not expressing it correctly in their language. Go figure.

    Anyway, all that claptrap being finished, good post and thread TChort. It has been done to death on BL but nowhere nearly in depth as you are going and I like that alot.

    People often make the assumption that similar subbstrates, and same enzymatic paths automatically lead to poetentiation. Inhibtion is a difficult thing for alot of folks but as a general rule, and it is a pretty relaxed rule, same and similar do the job. Methadone though has unique attributes in so many ways, and even so many ways within its metabolic path.

    The flavanoids in grapefruuit juice, the subject you touched on in the other thread, being a prime example.

    Fact is though, serum levels can be potentiated with methadone, as with just about any substance. The issue then becomes discernibility. Subjectivity is the overiding issue here. IF serum levels can be increased, and they can be in certain ways, then it all comes down to is it worth it because of effort and risks

    Another issue I see is safety. I mean, with the ultra-heavy sedation methadone causes, combined with longest half life of any opiate/opioid, why bother? To increase sedation? How could you? To compensate....for...LACK OF EUPHORIA (hahah)? Now that IS a great reason but with the otherwise heavy pschoactivity taking place with methadone by itself ...


    See, glutethemide potentiating codeine, or even promethezine potentiating codeine is something that will make a real difference on so many levels. Aside from the documented clinical facts there is an undeniable pschoactive component. Codeine on its own leaves alot to desire, yes? Methadone on its own also leaves something to be desired but in a much, much, much less discernible way.

    Anyway, that is meandering from your point which is attemtping to verify potentiatos more than evalusating the utility of engaging them so mauybe it is a moot point here.
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    #6
    There are so many ways Orphenadrine can effect Opioids in general (and Methadone in particular); strong CYP2B6 Inhibition is just one. Many ethanolamine class anti-histamines increase the positive subjective offects of Opioids in general, especially when injected. I can attest that Methadone during MMT does not usually create euphoria; some people claim to feel euphoria every day from their dose, some say they experienced euphoria in the beginning of MMT, but over time it went away despite dose increases, some people experience no euphoria from Methadone under any circumstances. Despite this wide range of experiences, Orphenadrine is considered to be a long-lasting euphoriogenic compound. It is also available as an injectable with various Opioids to improve analgesia, and make the treatment preferable to the patients compared to Opioids by themselves. I imagine the effect of Orphenadrine + Methadone IV would be very similar to that of IV Diconal (Dipapanone/Cyclizine). In both cases you have a potent anti-histamine and a Diphenylpropylamine opioid combined, leading to a highly sought physiological effect. Although that would be an extreme case, as oral Orphenadrine combined with oral Methadone should provide an adequately pleasurable experience given the right circumstances.

    The only people who could possibly do this safely are those with high tolerances and are dependant on a high dose of daily Methadone or are extremely competant when it comes to pharmacodynamics and how to respond to adverse reactions (i.e. intelligent and responsible people).

    I can't stress enough how dangerous this combination would be, and would say without a doubt that it is more dangerous to the mind and body than even Diconal, which is considered by many to be the most dangerous and hazardous combination- the main reason I think this is Cyclizine does not potentiate Dipapanone the way Orphenadrine would potentiate Methadone. An OD with Diconal would generally happen with the Cyclizine first, leading to seizures, hallucinations, delerium, coma. The OD with Methadone/Orphenadrine (oral and IV) would be an adverse Methadone reaction, oversedation leading to respiritory depression, coma and death. The dose-response curve present with Diconal is much more forgiving than the one with Methadone/Orphenadrine would be as well. The first dose of Orphenadrine/Methadone could be fatal, as very few people know of their particular enzyme make up, so if you were deficient in CYP2B6 enzymes, and dosed on this combination, the first dose would lead to extreme adverse effects and quite possibly death, whereas a single dose of Diconal would most likely not be enough to produce the adverse effects related to that combination (delerium, seizure, coma,etc).
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    #7
    Bluelighter rachamim's Avatar
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    There was a thread in another forum, jsut the other day, where they asked for peoples' favorite substances. Damn, I forgot all about Diconal, it has been gone so long. Pink heroin they used to call it when they worked it up. Pink Tar, but man that was good stuff. All these years, I feel like a senior citizen now.

    I liked though, that in your last post you raised the point at least 2 times that whast you are discussing is very dangerous, people need to be aware of that.

    Sure, there always going to be folks who try to do it betetr but to me, well you know my take on it I am sure.
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    #8
    Bluelight Crew negrogesic's Avatar
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    I have combined Norflex and Methadone orally, but never intravenously...
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    #9
    Quote Originally Posted by negrogesic
    I have combined Norflex and Methadone orally, but never intravenously...
    What was your impression?

    There was a thread in another forum, jsut the other day, where they asked for peoples' favorite substances. Damn, I forgot all about Diconal, it has been gone so long. Pink heroin they used to call it when they worked it up. Pink Tar, but man that was good stuff. All these years, I feel like a senior citizen now.

    I liked though, that in your last post you raised the point at least 2 times that whast you are discussing is very dangerous, people need to be aware of that.

    Sure, there always going to be folks who try to do it betetr but to me, well you know my take on it I am sure.
    Theres a reason there aren't many old Diconal users left
    Something about the UK and shooting pills. Recently all the jelly shooters, those people missing digits and toes from cooking up and banging that trash. I like this quote from an old McDermott Guide Usenet post:

    "Hopefully, as the Diconal experience retreats further and further back into
    the annals of folk memory, fewer people will experiment with this
    combination, but until then, I can only make one recommendation with regard
    to this substance: avoid it like HIV (or the plague.)"
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    #10
    Bluelighter rachamim's Avatar
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    No doubt but when done correctly it is, hands down, my favorite of the entire class.
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    #11
    Bluelighter THE_REAL_OBLIVION's Avatar
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    Wait wait wait wait a minute here guys.

    I often have fun searching for subjects discussed on bluelight, sometimes random, sometimes related to what i'm using. I'm on methadone but only for 8 more days as I will switch to suboxone then. Today I ate a 100mg orphenadrine citrate pill 5h45 - 6h after having my regular methadone dose. Am I going to OD/stop breathing now ? I feel totally normal....except that I had already potentiated the done 1h30 before dosing with 50mg hydroxyzine, which is something I do something as the hydroxyzine seems able to bring me a happy face and good warm feelings from methadone...


    I'm pretty goddamn scared and too tired to read all this even if I could understand what it all means...help.
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    #12
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    how about you research the effects of drugs before you take potentially life threatening combinations?

    you'll probably be fine as orphenadrine is basically just an antihistamine, its not going to cause methadone blood levels to jump through the roof.
    Guidelines for OD ||| OD Standards ||| OD Directory Read Me First! ||| NPD Rules
    Please read the links above or PM me if I lock your post. R.I.P. F28
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    #13
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    When I was on methadone I used to take Moclobemide and Xanax and I used to get high as a giraffes pussy... If you were to go the IV route with properly filtered physeptone or other filtered methadone you get a heroin like rush when you combine these three.
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    #14
    Bluelighter THE_REAL_OBLIVION's Avatar
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    Quote Originally Posted by sekio View Post
    how about you research the effects of drugs before you take potentially life threatening combinations?

    you'll probably be fine as orphenadrine is basically just an antihistamine, its not going to cause methadone blood levels to jump through the roof.

    Ok look, inb4 more RESEARCH YOU DOOFUS etc.

    I sprained my ankle and since orphenadrine is otc in canada i have used it often before even with other opiates, i noticed some synergy sure but I didn't think it was dangerous. Especially since it really sucks when I hurt myself on methadone, it's not like I have much choice to take th e pain away, we dont even have soma in canada, so usually its either orphenadrine, voltaren or flexeril in case of pain.

    Right now I can attest that yes, 100mg (just one pill) works and I have a medium-high body high which feels very awesome. I'm also on 60mg of methadone since ages, it's not a dosage I am not used of taking. So I think the warning might be a little exaggerated, which is the usual with most drug warnings in this world. Drugs.com doesn't say anything particular. I didn't know about this reaction before I took the orphenadrine like I said. There was no way in my mind such a weak muscle relaxer would have anything fun to give. My oxygen saturation is 99% my bp is 119/ 80 and my pulse is 91. (thankfully I have a pharmacy in front of my apartment, where I also get my doses). The pharmacist told me he never had anyone claiming to have problems with both. I called the hospital to talk to a nurse (with the 811 health service here in my province) and they told me that nobody ever died of this combo and that I shouldn't be scared of anything unless this was the first time taking methadone or first time taking this dose. None of that is occuring. I'm mostly surprised i'm feeling something positive from done for once.

    @aussie101 : holy shit! only canada and australia has moclobemide, I have tons here! I was scripted Manerix before as it was the only antidepressant i was wiling to try because it was a reversible MAOI and I heard how the regular old MAOI's were literally the best for depression. This one doesn't have dietary restrictions. What dosage of methadone were you using ? I was stockpiling my moclobemide lately because I have used it once for a pharmausca trip and it worked very well for that and if I ever needed a MAOI, well I had it there to make DMT work orally.


    I will not use it tonight, but i will take half a 150mg tablet one day and see. I gotta know, cos on the 20th i'm switching to suboxone and I won't be able to get high.at.all with that blocking thing that is buprenorphine.



    edit 2 : It seems most of the warnings are about Methadone when IV'd..


    I am quite nervous because for once I really do feel awesome effects related to the Methadone, hence why i'm scared. It's uncommon to feel this high from methadone when all it is supposed to do is make me feel normal...shit.
    Last edited by THE_REAL_OBLIVION; 13-02-2013 at 01:24.
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    #15
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    @THE_REAL_OBLIVION: moclobemide increases the amount of methadone retained in your body and reduces its breakdown by your body. I used to take 150mg every morning. Then 2mg Xanax. Then I would take my methadone. Since I am off it now I no longer take the combination, but towards the end of my dependence on methadone i was taking 80mg. In the last month of my dependence I got prescribed physeptone tablets and used to crush up and filter 80mg of the tabs through a filter wheel and put in a 10ml barrel connected to a cannula... Here in Aus, well Sydney any way there is injection centres you can go to and get all this equipment for free. I'd go there to use it. Very slowly and carefully push the plunger down and by the time the 10ml had gone down it felt just like heroin!! It was a good combo...

    If you are taking it orally you will get very noddy!! If i took my methadone normally i was on the nod all day with that combination!
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    #16
    Bluelighter THE_REAL_OBLIVION's Avatar
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    Quote Originally Posted by aussie101 View Post
    @THE_REAL_OBLIVION: moclobemide increases the amount of methadone retained in your body and reduces its breakdown by your body. I used to take 150mg every morning. Then 2mg Xanax. Then I would take my methadone. Since I am off it now I no longer take the combination, but towards the end of my dependence on methadone i was taking 80mg. In the last month of my dependence I got prescribed physeptone tablets and used to crush up and filter 80mg of the tabs through a filter wheel and put in a 10ml barrel connected to a cannula... Here in Aus, well Sydney any way there is injection centres you can go to and get all this equipment for free. I'd go there to use it. Very slowly and carefully push the plunger down and by the time the 10ml had gone down it felt just like heroin!! It was a good combo...

    If you are taking it orally you will get very noddy!! If i took my methadone normally i was on the nod all day with that combination!

    I am not shooting up Manerix or anything else, one of the reason why I got on methadone was because my right hand was becoming disgusting due to the huge swollen track mark I had there in october.


    But as for the rest good info. I feel alright....I was just SO surprised to feel this good from methadone, I thought there was no way I was gonna be safe. But I only took 1 pill (100mg) and 6 hours later after having my done.

    I'm gonna go lie down in my bed and nod...but not too much, will not let myself fall asleep.
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    #17
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    Quote Originally Posted by THE_REAL_OBLIVION View Post
    I am not shooting up Manerix or anything else, one of the reason why I got on methadone was because my right hand was becoming disgusting due to the huge swollen track mark I had there in october.


    But as for the rest good info. I feel alright....I was just SO surprised to feel this good from methadone, I thought there was no way I was gonna be safe. But I only took 1 pill (100mg) and 6 hours later after having my done.

    I'm gonna go lie down in my bed and nod...but not too much, will not let myself fall asleep.
    No no don't shoot up the manerix! I meant I just shot up the methadone. And do not shoot up xanax either!! lol
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    #18
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    Quote Originally Posted by aussie101 View Post
    No no don't shoot up the manerix! I meant I just shot up the methadone. And do not shoot up xanax either!! lol
    And i will not shoot up methadone either, my takehomes are mixed with orange juice, I can't even plug it.


    But this orphenadrine DEFINITELY boosts methadone, I,m nodding in and out in my bed, its scaring me i dont wanna fall asleep in my nod so i'm making coffee. I had never planned this, alll I wanted was to lose some of the pain from that sprained ankle of mine....

    I'll raise this issue when I see my methadone on the 20th when i will be switched to bupe. I have to make them aware of this even if it ruins the fun of some people. Tomorrow I will only take half my takehome and take another 100mg orphenadrine and see what happens.

    I usually just potentiate a little with hydroxyzine which works well, but this feels like a full on synthetic opioid buzz the kind I had when I was scripted 50mg Demerol pills back 5-6 years ago after a very painful nose surgery (removal of vegetations and correcting a deviated septum).


    This is the firs time I am overwhelmed by 'done. Even when I was taking xanax not scripted to me over this dose of 'done did I not nod and feel high like this. I am one of those rare patients allowed to continue taking his dose of benzos he was using before going on MMT (valium 10mg bid) because it had been WAY WAY longer that I had been tolerant/addicted to diazepam before I ever put a syringe in my arm or ever got high with an opiate other than codeine. I was able to take my 20mg of valium + 2-3-4mg of xanax at night and i'd just fall asleep soundly for 4-5 hours.

    Right now it's like....well I never felt like this, the closest was eating 200-250mg of Demerol + weed + valium, but I was expecting it. Right now I wasn't, I didn't feel an opiate high since I started on MMT (the first 2 months were fun but no way near this even).

    So right now its coffee and a lot of it...
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    #19
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    Quote Originally Posted by THE_REAL_OBLIVION View Post
    And i will not shoot up methadone either, my takehomes are mixed with orange juice, I can't even plug it.


    But this orphenadrine DEFINITELY boosts methadone, I,m nodding in and out in my bed, its scaring me i dont wanna fall asleep in my nod so i'm making coffee. I had never planned this, alll I wanted was to lose some of the pain from that sprained ankle of mine....

    I'll raise this issue when I see my methadone on the 20th when i will be switched to bupe. I have to make them aware of this even if it ruins the fun of some people. Tomorrow I will only take half my takehome and take another 100mg orphenadrine and see what happens.

    I usually just potentiate a little with hydroxyzine which works well, but this feels like a full on synthetic opioid buzz the kind I had when I was scripted 50mg Demerol pills back 5-6 years ago after a very painful nose surgery (removal of vegetations and correcting a deviated septum).


    This is the firs time I am overwhelmed by 'done. Even when I was taking xanax not scripted to me over this dose of 'done did I not nod and feel high like this. I am one of those rare patients allowed to continue taking his dose of benzos he was using before going on MMT (valium 10mg bid) because it had been WAY WAY longer that I had been tolerant/addicted to diazepam before I ever put a syringe in my arm or ever got high with an opiate other than codeine. I was able to take my 20mg of valium + 2-3-4mg of xanax at night and i'd just fall asleep soundly for 4-5 hours.

    Right now it's like....well I never felt like this, the closest was eating 200-250mg of Demerol + weed + valium, but I was expecting it. Right now I wasn't, I didn't feel an opiate high since I started on MMT (the first 2 months were fun but no way near this even).

    So right now its coffee and a lot of it...


    edit : today I took my 50mg or so methadone ( i sipped a little on my takehome yesterday, just a tiny sip) instead of 60mg. That never changes anything (I do not get sick). I've nodded very hard for the last 3 hours but since about 30 minutes, i feel totally sober and i mean SOBER not with methadone in my system not making me sick. Would inhibiting that liver enzyme with orphenadrine make my metabolizing of methadone faster ? Because, I'm really enjoying myself right now because sure nodding is fun but I got stuff to do like most other people

    I feel like...I feel like before I ever had any opiates for fun right now. It's weird. Thankfully I found this information when I was at a stable 'done dose since a long while. Please do not take orphenadrine with your methadone if the dosage was just upped. Very bad idea....I have nodded for 3 hours after eating a 100mg pill of orphenadrine and i am used to take 60mg of methadone a day since 3 months.
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    #20
    messing with methadone and potentiation sounds like a good recipe for accidental death.
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    #21
    Quote Originally Posted by the_milkman View Post
    messing with methadone and potentiation sounds like a good recipe for accidental death.
    Quoted for truth.
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