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DXM Dextromethorphan

 
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  #1  
Old 04-02-2011, 01:01
LayneStaley LayneStaley is offline
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DXM and Bupropion (Wellbrutin)

Ok so, my pet kitten has been on wellbutrin for a month, he was wondering if he could use DXM while on it, he knows its not an SSRI, but is this really dangerous? He plans on doing about 500-600 range. Which isn't a lot for him.
Sorry if this has been answered somewhere else, im new here. Thanks.
  #2  
Old 04-02-2011, 03:49
FinnishPharmer FinnishPharmer is offline
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Re: Dxm question?

Well, as far as swim can tell, there should not be a contraindication. Wellbutrin works primarily with dopamine and norapinephrine while DXM as a dissociative works on NDMA and sigma receptors. The primary reason why swim doesn't think there will be a contraindication is because almost all of DXMs effects are antagonist effects, meaning they stop neurotransmitter transmission. Serotonin syndrome is caused usually by serotonergic releasers alone or coupled with serotonin reuptake inhibitors. While swim doesn't see why an adverse reaction would arise, in the spirit of harm reduction, don't do it if swiy has any doubt. And also, if swiy does decide to do it, take a much lower dose, shoot for 1st-2nd plateau to test out the waters. Recreation is never worth bad health!

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extremely helpful. First line of good info. Ive found in an hour on the internet through the appropriate channels. Thanks!
  #3  
Old 04-02-2011, 17:11
Phungushead Phungushead is offline
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Re: Dxm question?

There are contraindications with this combination - Extreme caution is advised.

Wellbutrin (bupropion) is a potent CYP2D6 enzyme (which metabolizes dextromethorphan) inhibitor. CYP2D6 inhibition slows down the conversion of dextromethorphan --> dextrophan, and therefore increases the ratio of DXM to DXO, resulting in a more potent (but less pleasurable) trip with an increased amount of adverse side effects. Some users have reported that the combination of these two drugs can lead to experiencing effects for several days, and there have been reports of people on bupropion taking therapeutic doses of DXM and getting effects comparable to a low recreational dose level.

Would strongly recommend avoiding dextromethorphan if on bupropion, and for 1-2 weeks (or longer) after discontinuing use to allow it to clear out of your system.

Some further reading:

Inhibition of CYP2D6 activity by bupropion.
Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, Adson DE.

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Twin Cities Campus, Minneapolis, MN 55455, USA. kotly001@umn.edu

Quote:
Abstract

The purpose of this study was to assess the effect of bupropion on cytochrome P450 2D6 (CYP2D6) activity. Twenty-one subjects completed this repeated-measures study in which dextromethorphan (30-mg oral dose) was administered to smokers at baseline and after 17 days of treatment with either bupropion sustained-release (150 mg twice daily) or matching placebo. Subjects quit smoking 3 days before the second dextromethorphan administration. To assess CYP2D6 activity, urinary dextromethorphan/dextrorphan metabolic ratios were calculated after an 8-hour urine collection. Thirteen subjects received bupropion, and 8 received placebo. In those receiving active medication, the dextromethorphan/dextrorphan ratio increased significantly at the second assessment relative to the first (0.012 +/- 0.012 vs. 0.418 +/- 0.302; P < 0.0004). No such change was observed in those randomized to placebo (0.009 +/- 0.010 vs. 0.017 +/- 0.015; P = NS). At baseline, all subjects were phenotypically extensive CYP2D6 metabolizers (metabolic ratio <0.3); after treatment, 6 of 13 subjects receiving bupropion, but none of those receiving placebo, had metabolic ratios consistent with poor CYP2D6 metabolizers. Bupropion is therefore a potent inhibitor of CYP2D6 activity, and care should be exercised when initiating or discontinuing bupropion use in patients taking drugs metabolized by CYP2D6.
Guzey C, Norstrom A, Spigset O.
Department of Clinical Pharmacology, University Hospital, N-7006 Trondheim, Norway.
Quote:
Some data indicate that bupropion inhibits the cytochrome P-450 enzyme CYP2D6, but very little published data is available on the extent of this inhibition. The objective of the present study was to quantify this inhibition in a subject treated with bupropion for smoking cessation. Genotypically, the patient was a CYP2D6 homozygous extensive metabolizer (EM). His CYP2D6 phenotype was assessed using the test drug dextromethorphan before, during, and after treatment with bupropion. During treatment with bupropion, he clearly changed from the EM to the poor metabolizer (PM) phenotype. Although the results from a single patient should be interpreted with great caution, the extent of the interaction indicates that bupropion might be a CYP2D6 inhibitor as potent as the most powerful CYP2D6 inhibitors known, such as quinidine and paroxetine.
Quote:
MODERATE: bupropion ↔ dextromethorphan

Applies to:Wellbutrin XL (bupropion) and dextromethorphan

ADJUST DOSE: Coadministration with bupropion may increase the plasma concentrations of drugs that are metabolized by CYP450 2D6 (e.g., selective serotonin reuptake inhibitors; tricyclic antidepressants; some beta blockers, antiarrhythmics, and antipsychotics). The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by bupropion. Approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent are extensive metabolizers of CYP450 2D6 and may be affected by this interaction. In a study of 15 male volunteers who were extensive metabolizers of CYP450 2D6, pretreatment with bupropion (150 mg twice daily) increased the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and half-life of desipramine (50 mg single dose) by an average of 2-, 5-, and 2-fold, respectively. The effect was present for at least 7 days after the last dose of bupropion. In one case report, plasma levels of imipramine and its metabolite, desipramine, increased approximately fourfold in a 64-year-old woman following the addition of bupropion 225 mg/day. Plasma levels of desipramine were increased twofold more than the imipramine levels, which is consistent with the fact that desipramine is primarily metabolized by CYP450 2D6 while imipramine is also metabolized by other CYP450 isoenzymes. Similarly, a 62-year-old woman with no history of seizures developed a generalized tonic-clonic seizure in association with toxic trimipramine plasma levels following the addition of bupropion. No further seizures occurred following dosage reductions of both drugs.

MANAGEMENT: Caution is advised if bupropion must be used concomitantly with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Concomitant medications should be initiated at the lower end of the dose range. Clinical and laboratory monitoring may be appropriate for some drugs whenever bupropion is added to or withdrawn from therapy.

Source: hxxp://www.drugs.com/drug-interactions/dextromethorphan-with-wellbutrin-xl-844-0-440-2469.html


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great info, and nicely backed up with references!
  #4  
Old 04-02-2011, 23:23
FinnishPharmer FinnishPharmer is offline
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Re: Dxm question?

Quote:
Originally Posted by Phungushead View Post
There are contraindications with this combination - Extreme caution is advised.

Wellbutrin (bupropion) is a potent CYP2D6 enzyme (which metabolizes dextromethorphan) inhibitor. CYP2D6 inhibition slows down the conversion of dextromethorphan --> dextrophan, and therefore increases the ratio of DXM to DXO, resulting in a more potent (but less pleasurable) trip with an increased amount of adverse side effects. Some users have reported that the combination of these two drugs can lead to experiencing effects for several days, and there have been reports of people on bupropion taking therapeutic doses of DXM and getting effects comparable to a low recreational dose level.

Would strongly recommend avoiding dextromethorphan if on bupropion, and for 1-2 weeks (or longer) after discontinuing use to allow it to clear out of your system.

Some further reading:

Inhibition of CYP2D6 activity by bupropion.
Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, Adson DE.

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Twin Cities Campus, Minneapolis, MN 55455, USA. kotly001@umn.edu

Guzey C, Norstrom A, Spigset O.
Department of Clinical Pharmacology, University Hospital, N-7006 Trondheim, Norway.
Great Post! Swim didn't even think about that. He would guess that this would be a similar type of potentiation to grape fruit juices. This is why some people can react extremely differently to DXM then others. Some have little to none of this enzyme and trip very hard and others have a surplus and can't trip at all.
  #5  
Old 22-11-2012, 21:48
DrugDoctor DrugDoctor is offline
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Re: DXM and Bupropion (Wellbrutin)

Do not take DXM, if you have taked bupropion (Wellbutrin)! Trip is far more intens and psychotic. I found my self in a hospital whe took just therapeutical doses of DXM.
  #6  
Old 24-11-2012, 21:51
PowerfulMedicine PowerfulMedicine is offline
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Re: Dxm question?

Quote:
Originally Posted by FinnishPharmer View Post
Well, as far as swim can tell, there should not be a contraindication. Wellbutrin works primarily with dopamine and norapinephrine while DXM as a dissociative works on NDMA and sigma receptors. The primary reason why swim doesn't think there will be a contraindication is because almost all of DXMs effects are antagonist effects, meaning they stop neurotransmitter transmission. Serotonin syndrome is caused usually by serotonergic releasers alone or coupled with serotonin reuptake inhibitors.
DXM is actually a serotonin, dopamine, and norepinephrine reuptake inhibitor. It is also a serotonin and dopamine releasing agent due to its NMDA antagonism. DXM effects far more neuroreceptors than just NMDA and Sigma. And DXM is a Sigma agonist not an antagonist.

As long as bupropion does not effect serotonin, there should be no possibility of serotonin toxicity. But as posted earlier by Phungushead, bupropion is potent inhibitor of CYP2D6. So this could potentially be a dangerous combination. I would advise against this combination, especially if you have been on bupropion for a month since your CYP2D6 level are likely to be chronically low.

This does seem like it could be an interesting combination if a very low dose of both drugs are taken, but only after discontinuing the daily use and waiting a few weeks for your enzyme levels to return to normal. This could still be dangerous though and probably should not be attempted.
  #7  
Old 25-11-2012, 13:54
DrugDoctor DrugDoctor is offline
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Re: DXM and Bupropion (Wellbrutin)

Sorry for spelling mistakes in my previous message, I was writing in a hurry, and englis is not my mother tongue.

Like I said, I found myself in a hospital after takin bupropion (Wellbutrin) and dextromethorphan (DXM). The doses I used were 300 mg of bupropion (slow-release pills), and 50 ml of cough medicine containing 3 mg of DXM in one milliliter.

About half an hour something started to happen, and I quickly realised that it was because of my medications. After that I saw extremely real hallusinations, and my toughts were weird at least. My friend came to see mee, because he was worried. I talked with him via MSN in 30 minutes before he came to see me. When we went out, I stopped, and asked could we wait for the dog that is with us? There were no dog. One hour later, I felt physically so bad, that we had to call an ambulance. I woke up in a hospital next morning. Everything was OK, the trip was over and I was able to leave soon after waking up.

Reason for this was psychotic trip was, that in metabolism of bupropion and DXM they use the same enzyme. Bupropion boosts the effects of DXM, and also keeps it longer in your body.
  #8  
Old 29-11-2012, 05:47
PowerfulMedicine PowerfulMedicine is offline
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Re: DXM and Bupropion (Wellbrutin)

^DrugDoctor, 300mg of Bupropion is a relatively high dose and if it was time release then there would be a significant concentration of this drug in your body for a long time, so that might have factored into the intensity of your trip. But the description of your trip does not seem all that unusual. What you described is well with in the range of effects for DXM, but it does sound like there was more of a deliriant aspect than there would be in a normal robotrip.

It also doesn't sound like you were in any danger due to this combination since they released you from the hospital so fast. To me, it sounds like you felt bad and looked bad, so you and your friend freaked out and called the ambulance out of panic.

The only thing that sticks out about this trip is the intensity of it. There are plenty of other drugs that are commonly used to potentiate DXM by competing for the same enzymes. For instance, many people use Diphenhydramine (a CYP2D6 substrate/inhibitor) to potentiate DXM in the same way that Bupropion would. I can say from personal experience that Diphenhydramine does increase the intensity and duration of the trip. But not for such low doses of DXM.

Bupropion very well may be a much stronger inhibitor of CYP2D6 than Diphenhydramine, but your reaction seems to be much stronger than I would have expected.

So I have some questions. Do you have experience with recreational use of DXM and, if so, do you know whether you have an enzyme deficiency? If you are enzyme deficient, this story would make much more sense.

I still think that this combination could be "safe" with lower doses of Bupropion. But I am no doctor and I'm not suggesting that anyone try this potentially dangerous combination.
  #9  
Old 03-12-2012, 16:12
Mochaccino Mochaccino is offline
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Re: DXM and Bupropion (Wellbrutin)

Do the precautions about taking bupropion with DXM also apply to bromocriptine? I've heard many times that bromo is similar to bupropion in some ways, but I know that there are also important differences between the two. They're both SNRI's, but beyond that, I don't really know very much. Bromocriptine is not a recreational drug, or a common psychiatric drug, so I wouldn't be surprised if no one other than me has ever even mentioned it on this board. Hopefully someone here is willing to read up on bromocriptine and let me know if the combo is dangerous.

Mochaccino added 23 Minutes and 54 Seconds later...

Ugh...I meant that they're both dopamine agonists. It's DXM that's an SNRI.

Last edited by Mochaccino; 03-12-2012 at 16:12. Reason: Automerged Doublepost
  #10  
Old 03-12-2012, 16:48
pcp saved my life pcp saved my life is offline
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Re: DXM and Bupropion (Wellbrutin)

bupropion is an NDRI
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Old 04-12-2012, 06:41
Mochaccino Mochaccino is offline
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Re: DXM and Bupropion (Wellbrutin)

I REALLY need to know whether bromocriptine has the same issues.
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Old 05-12-2012, 18:25
PowerfulMedicine PowerfulMedicine is offline
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Re: DXM and Bupropion (Wellbrutin)

^You should have started a new thread to discuss this drug. Your question has nothing to do with the combination of DXM and Bupropion.

Secondly, you could have at least done a little research on your own. The Wikipedia entry for Bromocriptine clearly states that it is a strong Dopamine D2 agonist and a moderate agonist of Serotonin 5-HT1 and 5-HT2.

And as mentioned earlier, Bupropion is not a Dopamine agonist it is a Dopamine (as well as Norepinephrine) Reuptake Inhibitor.

If you would have actually read this thread, then you would have seen that possibility of interactions with DXM and Bupropion is not due to its Dopamine effects, but due to its metabolism. And if you had done any research on DXM you would have known that Dopaminergic drug don't cause adverse reactions with DXM, it is Serotonergic drugs that can cause problems.

From this little bit of research, you could have seen that any possible interactions between DXM and Bromocriptine would be due to its Serotonin agonist effects. But this shouldn't be too much of a problem since DXM can generally be safely combined with psychedelics like LSD, which is also an ergoline derivative and a Serotonin agonist.

Next time be more respectful and at least show that you are willing to do some of your own research. It is rude to just come out of no where demanding information and expecting someone to do all the work for you. Next time you might not be so lucky to find someone willing to help you. And UTFSE!
  #13  
Old 13-04-2013, 05:12
joey3tearz joey3tearz is offline
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Re: DXM and Bupropion (Wellbrutin)

My friend has this fear constantly for he takes welbutrin and aderral and has been for over 5 years so it doent matter if he stops for weeks before taking dxm. There is still a risk for serotonin syndrome. He has never jad this happen before so he generally doesnt worry to mich however one day after using 600 mg of dxm the previous night he experienced a migrain from hell that lasted for 2 hours . My cousin was actually in tears from the pain. He doesnt know if this may have somthing to do with serotonin or not, so be careful and stay safe
-j3t
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Old 08-05-2014, 21:55
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Re: DXM and Bupropion (Wellbrutin)

My personal unscientific view: Low doses of DXM with standard prescribed bupropion doses can give prolonged borderline recreational and therapeutic effects, the more DXM the more intense the buzzed effects...very useful for people looking for just a little more than bupropion alone can give therapeutically speaking-both from ponentiation and from extra serotonin I imagine. Taking several hundred milligrams of DXM for a higher plateau trip might be dangerous or unpleasant, due to the prolongation of the effects could last way longer than desired. Also leaves a more prolonged afterglow/hangover effect (pleasant in my experience). Long term effects of regular use might be negative, the afterglow is reminiscent of familiar supposedly neurotoxic substances. Too much can leave you a little loopy for several days afterward. Not sure if or how these effects will manifest for someone who has not been taking bupropion regularly longterm.

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