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N&PD Moderators: Skorpio | someguyontheinternet
DXM and Dopamine
- Thread starter laCster
- Start date
themdyaunome
Bluelighter
There's no clear evidence yet whether or not DXM affects your dopamine levels, as studies have shown with other drugs that act on the same receptors, both raise dopamine levels and lower them. Not enough research has been done with DXM to prove whether or not dopamine levels are increased or decreased, though it definitely does one of the two. However, it would be fair to assume that dopamine levels are increased when taking DXM, causing the feeling of euphoria. It also acts upon other hormones associated with dopamine such as seratonin. It is not safe to mix DXM with other medicines that affect your seratonin levels, such as anti-depressants and certain psychedelic drugs, because it has been known to cause seratonin syndrome. DXM also has also shown to have an adverse effect on melanin levels as well.
EDIT: Just had to throw this funny story in here. Many years ago my brother and his friend were taking Coricidin almost daily, and his friend wound up in the hospital two or three times due to the amount of guaifenesin ingested. Anyways, one night I heard something at my bedroom door around 2 or 3 in the morning. I figured it was my cat wanting to come in. I then listened more closely and could hear giggling. I open the door to find my brother and his friend licking my wooden door. They claimed it "felt awesome."
EDIT: Just had to throw this funny story in here. Many years ago my brother and his friend were taking Coricidin almost daily, and his friend wound up in the hospital two or three times due to the amount of guaifenesin ingested. Anyways, one night I heard something at my bedroom door around 2 or 3 in the morning. I figured it was my cat wanting to come in. I then listened more closely and could hear giggling. I open the door to find my brother and his friend licking my wooden door. They claimed it "felt awesome."
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MyDoorsAreOpen
Bluelight Crew
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DXM is a prodrug for detrorphan in vivo, and dextrorphan is a modest NMDA receptor antagonist. NMDA receptor antagonism upregulates dopamine receptors. This is what causes the increased ability to feel pleasure and motivation after coming down from a DXM trip. I've never heard anything about DXM increasing dopamine release during its peak of action, directly. It's probably minimal at best.
Also, DXM has been shown to reduce the dopamine release of morphine.Supposedly. I don't believe DXM to be a recreational drug, rather an "experience" which is to experienced at the right time, which is rare. I will say that DXM has never caused any direct euphoria in anyone I have seen try it, so that and the morphine thing convince me it does not actually release dopamine.
... Does your name start with a T???(it's a serious question...)
... Does your name start with a T???(it's a serious question...)
MagickalKat777
Bluelight Crew
Low doses of DXM are close to being on par with MDMA for me and a number of people that I know. Dextromethorphan has been found to be active BEFORE it is turned into dextrorphan which implies that it has its own effects (a perfect example is that dextrorphan doesn't release serotonin on its own, at least from my own experiments with DXO and MDMA versus ONE experiment with 150mg of DXM and 100mg of MDMA which I will never repeat - came quite close to full blown serotonin syndrome that time) - also if you read the literature, people that are CYP2D6 deficient have entirely different experiences with DXM (besides the long life of the drug) than those that are not CYP2D6 deficient. I wouldn't be surprised if dopamine was released by DXM before it is converted to DXO. I have also experimented with cimetidine and DXM and found that high dose DXM with cimetidine is also quite euphoric for a number of hours - noting that CYP2D6 is inhibited by cimetidine.
I used to take low dose (200mg approximately) DXM and go dance all night and it was quite similar to a roll but quite a heavy bodyload (tachycardia, much more likely to vomit, higher temperature, etc) - doing the same with higher plateaus of DXM dosing would lead to a full blown psychedelic trip that still retained much milder tachycardia and it felt like a lighter overall bodyload - don't ever ask me to try to dance or talk on 3rd/4th plateau trips though.
(zonk)
Bluelighter
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Why is there all this dxm-dopamine speculation, it most certainly is %100 a DRI. It has a speedyness that is even more powerfull than pcp stimulation which is more profound than k which has almost a sedating effect so its a way to meassure/compare dopamine effect. Infact I have rolled off dxm with quite a bit of nystigmas/bruxism.
this is complete utter bullshit. i am on DXM and oxycodone right now. a lower dosage of oxy infact, and it feels 10x times stronger
but no my name starts with an R
source?? in all my studying, i have never found anything about DXM being a dopamine reuptake inhibitor
MagickalKat777
Bluelight Crew
Here is an old (but very good) thread on DXM's assumed MoA - http://www.bluelight.ru/vb/threads/166240-Dextromethorphan-Mechanism-of-Action
lorne667 - yeah I was never dumb enough to try cimetidine and MDMA, just DXM which was dumb enough (albeit much lower dose than I would usually take it was still stupid). It does help to prove my point though. Dextromethorphan is an active drug on its own and it makes sense if you think about the "plateaus" of DXM. Maybe at lower doses, not as much DXM gets nailed by CYP2D6 and converted to DXO - even still, DXO is about 40% more potent by weight in my experiments than DXM. I never tried mixing the two together because I really didn't like the experience of pure DXO that much. Extremely cold. DXM at any level has at least some euphoria for most of its users or it would have died like salvia. Just saying.
lorne667 - yeah I was never dumb enough to try cimetidine and MDMA, just DXM which was dumb enough (albeit much lower dose than I would usually take it was still stupid). It does help to prove my point though. Dextromethorphan is an active drug on its own and it makes sense if you think about the "plateaus" of DXM. Maybe at lower doses, not as much DXM gets nailed by CYP2D6 and converted to DXO - even still, DXO is about 40% more potent by weight in my experiments than DXM. I never tried mixing the two together because I really didn't like the experience of pure DXO that much. Extremely cold. DXM at any level has at least some euphoria for most of its users or it would have died like salvia. Just saying.
themdyaunome
Bluelighter
While I do not doubt that DXM has an effect on dopamine levels, in fact I am almost positive it does, I have done much research on the topic and the medical/science field has not diagnosed the effects of DXM as thoroughly as they could, and the question of whether or not it does effect dopamine levels, in the medical field at least is not 100% confirmed, therefore you cannot 100% say it does or it doesn't. Just putting that little bit of knowledge out there for you, though I cannot see myself how it couldn't increase dopamine levels. You'll notice on the comeup the feeling of euphoria as long as you stay away from too high of a dose, that is my experience with the drug at least. But everyone's body and mind are different; some people like cocaine, some prefer heroin...and like I said in my post above, DXM is closely related to other drugs that bind on the same receptors and do increase the levels of dopamine in the brain.
EDIT: thank you for pointing that out laCster. I know I should have taken basic pharmacology english in college. Serotonin, serotonin, serotonin. There we go!
EDIT: thank you for pointing that out laCster. I know I should have taken basic pharmacology english in college. Serotonin, serotonin, serotonin. There we go!
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sekio
Bluelight Crew
In my eyes DXM is a fairly powerful SNRI plus sigma-agonist plus NMDA-blocker, the norepinephrine reputake inhibition does provide a "speedy edge" and I think it's responsible for potentiation of stimulants/opioids. I don't think it's a DRI though.
MagickalKat777
Bluelight Crew
DXM is really two different drugs... DXM is active on its own - I proved that myself. Feel free to repeat with DXM. DXO sucks though and I had pure shit from SA. Note that is Sigma for the S. They are ENTIRELY different chemicals. If you inhibit the liver on a short term basis (I DO *********NOT********* recommend this - what I did could have killed me because cimetidine is a drug that inhibits MUCH more than just CYP2D6) then the DXM doesn't get broken down and you get a longer trip (it gets annoying after the 6 hour mark - its not worth it once again, your body is already wiped the fuck out after you take a *normal* 2nd or 3rd plateau dose - if you really want to experience DXM for a longer time, get a 5 ounce bottle of Delsym and drink that and tell me it didn't suck) and an entirely different experience. DXM IME is actually quite euphoric at lower doses and with the cim, it was EXTREMELY euphoric, almost better than a roll until my body flipped out about the inhibition of the enzymes and I got extremely sick. I don't ever throw up and I threw up for hours after my body caught up. Pure DXO... I don't really know how to explain it... It's like ketamine and PCP had a bastard child that screamed all the time... my hearing was highly impaired, my visual senses were impaired, my tactile senses were impaired, however, I never really got caught up in the full-blown DXM experience. There were visuals in my peripheral but nothing otherwise. It felt like a really bad night drinking. Very cold. There was a very strong dysphoria the two times I tried it before I flushed the other 5 grams. It was a terrible experience. I think they have an Erowid experience somewhere in there about Dextrorphan. Mine pretty closely mirrored it. The two together is the real magic and in my *personal* experience I would be FLABBERGASTED if DXM isn't active on its own AND has dopamine properties. I would never have done it for a year straight, even at work (host at Applebee's) if it didn't feel good.
EDIT: Does DXM on its own have dopamine activity? I think it does. Nobody has done the proper testing to prove it. There is a reason for this. For one DXM is abused enough but there is its optical? isomer levomethorphan which is a powerful opiate agonist (in the form of levorphanol IIRC) and if someone did the work I'm sure we could turn DXM into LVM. On top of that, its "recommended" use is as an antitussive (even though studies have proven it to be no better than placebo, we still have a drug that was specifically excluded from scheduling for its use in OTCs. Don't fuck it up) prevents research into the DXM -> DXO and beyond science.
EDIT: Does DXM on its own have dopamine activity? I think it does. Nobody has done the proper testing to prove it. There is a reason for this. For one DXM is abused enough but there is its optical? isomer levomethorphan which is a powerful opiate agonist (in the form of levorphanol IIRC) and if someone did the work I'm sure we could turn DXM into LVM. On top of that, its "recommended" use is as an antitussive (even though studies have proven it to be no better than placebo, we still have a drug that was specifically excluded from scheduling for its use in OTCs. Don't fuck it up) prevents research into the DXM -> DXO and beyond science.
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sekio
Bluelight Crew
Yeah and if someone did the work they could turn my turds into gold ingots too - stereochemistry doesn't work like that
themdyaunome
Bluelighter
That's a bit funny. I just bought a 5oz bottle of delsym about ten days ago not knowing it was a sort of time-released form. I have taken smaller doses of dxm when in opiate withdrawals which made me feel better, and I was about 5 days off suboxone, and figured I might as well get fucked up off of it one more time. I did it several times when I was younger but not in years. Anyways I figured this would at least give me a decent 3rd plateau feeling if not more intense(it was about 12mg/kg), yet I just felt out of it for two days straight. No positive side effects like I used to get when taking robotussin. I just felt tired, i felt like I couldnt move and was completely out of it in a drunken way, though no visual hallucinations were noticed. Definitely wasn't worth it.
do you ( or anyone else) know how much DXM is converted into DXO, or the amount converted depends on a person's velocity at which their 2D6 enzymes process?
Deleted member 175441
Bluelighter
grapefruit juice is supposed to inhibit the metabolism of dxm>dxo correct? Well when i tried drinking white grapefruit juice before tripping on 300 mg of dxm i think was the dose, it got me fucking retarded high. 8)
Dondante
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MagickalKat777 said:
Interesting, but surprising...check out the study below.
Zawertailo LA, Tyndale RF, Busto U, Sellers EM. Effect of metabolic blockade on the psychoactive effects of dextromethorphan. Hum Psychopharmacol. 2010 25(1):71-9.
OBJECTIVE:
Variation in the activity of cytochrome P450 2D6 (CYP2D6) affects the pharmacokinetics and effectiveness of dextromethorphan (DM), because it controls the production of dextrorphan, an active metabolite, with higher affinity for the NMDA receptor than the parent compound. This study examined whether pharmacological inhibition of CYP2D6 activity with quinidine would mimic the genetic mutation and thus also alter the psychoactive effects of DM.
METHODS:
In a single-blind, within-subjects study, eight healthy volunteers (all homozygous for the wild type allele for CYP2D6) received placebo and varying doses of DM, both with and without quinidine pre-treatment. Pharmacokinetic and pharmacodynamic measures were assessed at baseline and every hour post-drug for 6 h.
RESULTS:
Compared to the no quinidine condition, quinidine pre-treatment decreased the area under the dose-response curve on subjective measures of positively reinforcing effects (e.g., euphoria, p < 0.04; drug liking, p < 0.05), and was significantly greater for measures of dysphoria (e.g., unpleasantness, p < 0.02). These changes corresponded to increased DM and decreased dextrorphan plasma concentrations.
CONCLUSIONS:
Compared to DM alone, quinidine pre-treatment inhibited DM metabolism and changed its subjective effects, demonstrating that the psychoactive properties of DM are a function of drug metabolism. These results demonstrate the relationship between CYP2D6 activity, plasma drug levels, and psychoactive drug effects, and have implications for both the abuse liability and therapeutic utility of DM.
Here, 2D6 inhibition, which leads to accumumlation of DM (decreased conversion to DXO), was associated with increased measures of dysphoria and decreased measures of drug liking and euphoria. My understanding is that a similar phenomenon occurs in poor metabolizers who experience dysphoric effects from higher doses of DM.
Interestingly, the above combination has recently been put in a pill and marketed (as Nuedexta) for treatment of a type of affect dysregulation called pseudobulbar affect. My sense is that at low doses it essentially functions as an SSRI.
