DXM Brain Damage

[idontlove]

http://www.erowid.org/chemicals/dxm/dxm_health1.shtml

Can someone verify if this article is mostly bullshit or not?
If his claims were true, DXM would be just as bad or worse than using inhalants in terms of brain damage, and if huffing gasoline is frowned upon in the drug community, then why aren't dissociatives?

 

[PepperSocks]

It says this at the top:

Erowid Note: William White retracted the conclusions of this document in 2004

Check out the links right under that text.

Although I don't believe DXM is as benign as serotonergic psychedelics.

 

[hendrix62892]

of all psychedelics(if thats what you wanna call it) it is by far the worst for your health.i had a buddy who OD on it,if you can OD from a normal dose i dont think anyone should be taking it and urge all of you not to.

 

[helium-4]

Neuropsychotoxicity of abused drugs: potential of dextromethorphan and novel neuroprotective analogs of dextromethorphan with improved safety profiles in terms of abuse and neuroprotective effects.

Shin EJ, Lee PH, Kim HJ, Nabeshima T, Kim HC.

Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.

Drug abuse involving dextromethorphan, an antitussive, has been a social problem in various geographic locations since the 1960s. Ironically, high doses of the drug confer neuroprotective activity with central nervous system and behavioral effects. Accumulating evidence suggests that metabolism to phencyclidine-like dextrorphan is not essential for the neuroprotective activity of dextromethorphan. Here, we review the neuroprotective properties of dextromethorphan and its potential for abuse and the potential neuroprotective effects of the drug's analogs and 3-hydroxymorphinan, a metabolite of dextromethorphan. These compounds may provide a novel therapeutic direction for the treatment of neurodegenerative diseases such as convulsive or parkinsonian-like disorders.

Neuroprotective profile of dextromethorphan in an experimental model of penetrating ballistic-like brain injury.

Shear DA, Williams AJ, Sharrow K, Lu XC, Tortella FC.

Walter Reed Army Institute of Research, Department of Applied Neurobiology, Silver Spring, MD 21045, USA. [email protected]

Dextromethorphan (DM) has been well-characterized as a neuroprotective agent in experimental models of CNS injury. The goal of this study was to determine the neuroprotective profile of DM in a military-relevant model of penetrating ballistic-like brain injury (PBBI). In an acute (3 day) dose-response study, anesthetized male Sprague-Dawley rats were exposed to a unilateral frontal PBBI with DM (0.156-10 mg/kg) or vehicle delivered as an i.v. bolus from 30 min to 48 h post-injury. In a follow-up (7 day) experiment, the 10-mg/kg bolus injections of DM were administered in conjunction with a 6-h infusion (5 mg/kg/h). DM bolus injections alone produced a dose-dependent improvement in motor recovery on a balance beam task at 3 days post-injury. However, more rapid recovery (24 h) was observed on this task when the bolus injections were combined with the 6-h infusion. Moreover, the DM bolus/infusion treatment regimen resulted in a significant (76%) improvement in cognitive performance in a novel object recognition (NOR) task at 7 days post-injury. Although post-injury administration of DM (all doses) failed to reduce core lesion size, the maximum dose of DM (10 mg/kg) was effective in reducing silver-stained axonal fiber degeneration in the cortical regions adjacent to the injury.

Dextromethorphan as a potential neuroprotective agent with unique mechanisms of action.

Werling LL, Lauterbach EC, Calef U.

The Institute for Biomedical Sciences, The George Washington University Medical Center, Washington, DC, USA.

BACKGROUND: Dextromethorphan (DM) is a widely-used antitussive. DM's complex central nervous system (CNS) pharmacology became of interest when it was discovered to be neuroprotective due to its low-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonism. REVIEW SUMMARY: Mounting preclinical evidence has proven that DM has important neuroprotective properties in various CNS injury models, including focal and global ischemia, seizure, and traumatic brain injury paradigms. Many of these protective actions seem functionally related to its inhibitory effects on glutamate-induced neurotoxicity via NMDA receptor antagonist, sigma-1 receptor agonist, and voltage-gated calcium channel antagonist actions. DM's protection of dopamine neurons in parkinsonian models may be due to inhibition of neurodegenerative inflammatory responses. Clinical findings are limited, with preliminary evidence indicating that DM protects against neuronal damage. Negative findings seem to relate to attainment of inadequate DM brain concentrations. Small studies have shown some promise for treatment of perioperative brain injury, amyotrophic lateral sclerosis, and symptoms of methotrexate neurotoxicity. DM safety/tolerability trials in stroke, neurosurgery, and amyotrophic lateral sclerosis patients demonstrated a favorable safety profile. DM's limited clinical benefit is proposed to be associated with its rapid metabolism to dextrorphan, which restricts its central bioavailability and therapeutic utility. Systemic concentrations of DM can be increased via coadministration of low-dose quinidine (Q), which reversibly inhibits its first-pass elimination. Potential drug interactions with DM/Q are discussed. CONCLUSIONS: Given the compelling preclinical evidence for neuroprotective properties of DM, initial clinical neuroprotective findings, and clinical demonstrations that the DM/Q combination is well tolerated, this strategy may hold promise for the treatment of various acute and degenerative neurologic disorders.

Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain.

Carliss RD, Radovsky A, Chengelis CP, O'Neill TP, Shuey DL.

University of South Alabama, Mobile, AL 36604, USA. [email protected]

Dextromethorphan is a widely used antitussive agent, also showing increased recreational abuse. Dextromethorphan and its metabolite dextrorphan are non-competitive antagonists at the N-methyl-d-aspartate (NMDA) receptor ion channel. Single doses of some NMDA receptor antagonists produce neuropathologic changes in neurons of the retrosplenial/posterior cingulate cortices (RS/PC), characterized by vacuolation or neurodegeneration. To determine whether dextromethorphan produces these characteristic lesions, dextromethorphan was administered orally either as a single dose of 120mg/kg to female rats, or daily for 30 days at doses of 5-400 mg/(kg day) to male rats and 5-120mg/(kg day) to female rats. Brains were examined microscopically for evidence of neuronal vacuolation (4-6h postdose) and neurodegeneration ( approximately 24 or 48h postdose). Administration of dextromethorphan at 120mg/(kg day) in females, and at > or =150mg/(kg day) in males produced marked behavioral changes, indicative of neurologic effects. Mortality occurred at the highest doses administered. There were no detectable neuropathologic changes following single or repeated oral administration of dextromethorphan at any dose. Administration of MK-801 (9mg/kg) produced both cytoplasmic vacuolation and neuronal degeneration in neurons of the RS/PC cortex. Thus characteristic neuropathologic changes found with more potent NMDA receptor antagonists do not occur following single or repeated oral administration of dextromethorphan.

I wasn't able to find any evidence supporting any form of brain damage resulting from the use of DXM. Only things I could find is it's use as a neuroproctective agent.

 

[Captain.Heroin]

DXM can cause brain damage. If you take it less than once every 2 weeks I can't imagine you would get any brain damage if you take precautions (only DXM as an active ingredient in the products you consume, for example). If you take it daily for prolonged periods, I'm sure you'll have brain damage that is similar to other dissociative abuse (i.e. ketamine).

 

[helium-4]

I haven't seen any evidence what so ever supporting brain damage being caused by DXM. Can you please post sources to legitimize your claim? The evidence i posted above says the contrary, as it has been seen to be neuroprotective in different manners.

 

[madswagga]

Know a buddy who used to down 3 big bottles of delsym and two tussins everytime he'd trip. did it for a couple months straight couple times a week. got sober went to a psychiatrist did a pet scan and he had a couple lesions over his cortex. couldnt remember good for awhile. if needed i can source

 

[helium-4]

I will say that prolonged exposure or high doses of NMDA antagonist have been shown to produce neurotoxcity in the frontal regions of the brain [1]. This example being ketamine induced neurotoxcity in prenatal monkeys. I'm sure I can find more sources to go along with this. This neurotoxcity has been shown to be able to be "prevented/treated by certain anticholinergic drugs or by diazepam and barbiturates, which act at the gamma-aminobutyric acid (GABA) receptor-channel complex and are known to suppress the psychotomimetic symptoms caused by ketamine. Thus, it may be possible to prevent the unwanted side effects of NMDA antagonists, thereby enhancing their utility as neuroprotective drugs" [2]. So in sum, it may be that in the case of DXM there may be a risk of neurotoxicity due to it's NMDA antagonism, but likely it'll be from prolonged or high dose exposure. I feel there would be more reports of neurotoxicity caused by DXM normal recreational or low dose exposure in infrequent use if it was a problem. If you are concerned about neurotoxicity from DXM, I'd say take some diazepam as it is likely the easiest drug a layman can get there hands on in the prevention of neurotoxicity.

1- Int J Dev Neurosci. 2009 Nov;27(7):727-31. Epub 2009 Jul 4.
Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain.
Zou X, Patterson TA, Divine RL, Sadovova N, Zhang X, Hanig JP, Paule MG, Slikker W Jr, Wang C.
Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.

2- Science. 1991 Dec 6;254(5037):1515-8.
NMDA antagonist neurotoxicity: mechanism and prevention.
Olney JW, Labruyere J, Wang G, Wozniak DF, Price MT, Sesma MA.
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.

 

[chaoticc]

Know a buddy who used to down 3 big bottles of delsym and two tussins everytime he'd trip. did it for a couple months straight couple times a week. got sober went to a psychiatrist did a pet scan and he had a couple lesions over his cortex. couldnt remember good for awhile. if needed i can source

Shit, I can see why he developed lesions.
I personally have tripped 100-200 times on dxm, and haven't noticed anything wrong with my well being.(besides anxiety)

I could very well have lesions in my brain and not know it, but im still just as smart, if not smarter than before the drugs.

 

[madswagga]

ya but how much you do those 200 times? also he did alotta speed with it in those days. may have contributed. i've looked into it alot (asking neurologists n professors) and have heard of brain damage. good thing tho is because its usually only on the surface of the brain (the cortex) the brain can heal itself if u give it time

 

[bighooter]

kurt cobain used to take dxm all the time.................
and look how messed up he was

I think alot of ketamine these days is cut with DXM, because the stuff we're getting in my area doesnt feel like K although tastes like it, has a slightly diferent high

 

[kracks]

you cant snort DXM, so its a useless K substitute

 

[Amberthefrog]

I think alot of ketamine these days is cut with DXM, because the stuff we're getting in my area doesnt feel like K although tastes like it, has a slightly diferent high

I've tried two VERY different types of ket; I think the difference is one is just the S isomer (the good bit) and the other is a racemic mixture. This makes sense as the later ket is far, far, far easier to find and most medical ketamine is indeed racemic. However the enantiomerically pure S isomer IS also used in medicine, when I got this it came (originally) from an anesthetist.

It would make sense that, when used as a human anesthetic, the S isomer is preferred. The R isomer produces more nausea, which is one of the main things you want to avoid in a surgery.

For me, 'normal' ket is simply recreational in nature at low-medium doses - with a hint of something more. At high doses it becomes a LOT more dissociative and psychedelic. When I had the other stuff I found it pretty psychedelic at any dose.

Strangely I find DXM psychedelic in nature at even low doses.

I've always been somewhat doubtful of the Olney's lesions claim. Why?

1) They have never been observed in humans.
2) The study involved injecting large doses of MK-801 into the brains of rats.
3) The guy retracted his claims.

I find it all tenuous at best, I mean MK-801 ISNT PCP, much less ketamine or DXM. Even if they do all work through NMDA antagonism, doesn't mean they all share exactly the same modes of action. Has it actually been shown that NMDA antagonism was responsible for the lesions? I don't know much about
MK-801 to be honest. Even if it is a side effect of NMDA antagonism, the study tells us nothing about potential brain damage from lower doses in non IV routes. It also doesn't tell us if the effect occurs in humans.

I don't find it at all hard to believe that NMDA antagonists can produce some level of brain damage, I just find this study somewhat ludicrous.

 

[Ismene]

ya but how much you do those 200 times? also he did alotta speed with it in those days. may have contributed. i've looked into it alot (asking neurologists n professors) and have heard of brain damage. good thing tho is because its usually only on the surface of the brain (the cortex) the brain can heal itself if u give it time

Yeah but if you ask a professor who doesn't do drugs he's extremely likely to say "Yeah it causes brain damage" simply to put you off taking illegal drugs. People are like that arn't they.

As for any genuine evidence that these drugs cause brain damage in humans - there isn't any. When you look into it what you usually find is they injected massive quantities directly into mice brains every 4 hours for 20 days at a time, then cut the mice brain open, saw something that didn't look the same and concluded "Look dude, brain damage".

Whether a few damaged cells have any relevance to brain damage is another question entirely - brain cells are dying all the time but you never notice because the brain is a living, self-regulating thing.

Even the mice they claim have "brain damage" - my guess is if you released them into the wild they would lead perfectly healthy normal mice lives even with their so-called "brain damage".

 

[Amberthefrog]

As for any genuine evidence that these drugs cause brain damage in humans - there isn't any. When you look into it what you usually find is they injected massive quantities directly into mice brains every 4 hours for 20 days at a time, then cut the mice brain open, saw something that didn't look the same and concluded "Look dude, brain damage".

Whether a few damaged cells have any relevance to brain damage is another question entirely - brain cells are dying all the time but you never notice because the brain is a living, self-regulating thing.

Well put!

 

[sir_thizzalot]

We really don't have proof it causes brain damage? I've always been under the impression it's horrible for you..
I had a friend that got addicted to it, and I didn't see him when he was addicted to it, just after(he didn't do much else durring the time he was taking it, other than smoke some. And I was gone for a long time that's why I hadn't seen/talked to him), and w/o knowing he had been my thoughts were, "wow, this guys become a total fucking idiot, wtf happened?". Then I was told by one of his friends he got addicted to DXM(wasn't on it when I talked to him) and hadn't been doing much else while he was addicted but became pretty stupid.

 

[morbiddoctor]

Being addicted to it he was most likely dosing a few times a week. Which although there is no evidence to suggest that it causes brain damage, I highly doubt you're doing yourself any favors. I'm surprised I'm not retarded. I was doing it a few times a week for a while. This was CCC however. I know.

 

[Jesusgreen]

Dissociatives can definitely cause brain damage of some sort with extensive daily use of large amounts, however the majority of the time I'd say you shouldn't be concerned. Most of the negative side effects you will experience with heavy use will fade after a short time of ceasing your use, and while it is possible to do yourself some permanent damage you would really have to be using excessive amounts for a very long period of time. I'm not sure of the exact amounts of time or the exact dosages with DXM that would be required to cause permanent brain damage, however with Ketamine I can say you will see kidney and bladder damage (since Ketamine is an irritant unless combined with saline solution via IV) long before you will suffer any mental issues whether temporary or permanent.

If you are using DXM often but not in large amounts and you take regular breaks you have nothing really to worry about aside from temporary short term memory problems. If however you are using Ketamine, consider taking longer breaks as the kidney and bladder damage it can cause can be very serious.