Talk:Olney's lesions

Discredited?

I'd like to see the paper you're talking about here where Olney discredits the link between dissociatives and Olney's lesions. This is important, and I've looked through the internet to find whatever this recent reversal is based on. If anyone knows, please elaborate on that. Jolb 02:21, 14 September 2006 (UTC)

However, Olney's Lesions have now been discredited by the original author of the paper as an attempt to scare people away from DXM abuse (false it has not been discredited or disproven)

I have just a very extensive research on that statement. Erowid (notable drug vault), his claimed that Olney's Lesion DOES occur [1]. It has been proven to occur in rats. A google search on Olney's Lesions and being discredited or disproved brought no results. Valoem ^talk 21:22, 14 September 2006 (UTC)

Did you not notice when you read that article that Will White has followed up to it and retracted the claims made in the article you linked to? In the reference you cite (and mistakenly attribute to Erowid), it says right at the start of the document, "Erowid Note: William White retracted the conclusions of this document in 2004." It then goes on to refer the reader to three papers which contradict White's claims (Anderson, 2003; Carliss et al., 2007), including a document written by White (2004) himself. Carliss et al. (2007) is a research article that involved giving rats 120 mg/kg dextromethorphan (orally) once and examining their brains 4 hours later, or repeatedly oral administration of dextromethorphan in doses of upto 400 mg/(kg/day). No evidence of vacuolation or neurotoxicity was found in the retrosplenial cortex or posterior cortex (i.e. where Olney saw neurotoxic changes). Anderson (2003) is a criticism of the "this is your brain on dissociatives" that you cited. It just points out that White doesn't have sufficient evidence to claim that DXM definitely causes brain damage (and Onley agrees in a personal communication). The third document is White's (2004) response to Anderson, in which White retracts his claim that DXM causes Olney's lesions.

I'd also like to point out that someone wrote that the vacuoles are "irreversible" but this simply is incorrect. Whoever wrote that should actually read Olney's original research.

However, Olney's research on NMDA antagonist neurotoxicity certailny has not been discredited. There was some speculation that White wrote his "this is your brain on dissociatives" because he thought he had brain damage from DXM and wanted to make sure to keep people away from it, so there was speculation that White's 1998 document was just an attempt to scare people away from DXM abuse. However, it's quite clear that Olney et al. (1989) showed that NMDA antagonists cause neuronal vacuolation in rats.

References (1) Anderson C. (2003) [The bad news isn't in.] (Accessed 23 October 2010) (2) Carliss RD, Radovsky A, Chengelis CP, O'Neill TP, and Shuey DL. (2007) Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain. Neurotoxicology. 28: 813 - 818. PMID: 17573115 (3) Olney JW, Labruyere J, Price MT. (1989) Pathological Changes Induced in Cerebrocortical Neurons by Phencyclidine and Related Drugs. Science. 244: 1360 - 1362. PMID: 266026 (4) White W. (2004) Response to "The Bad News Isn't In": Please Pass the Crow (accessed 23 October 2010) AlkaloidMan (talk) 03:56, 24 October 2010 (UTC) AlkaloidMan

Thanks alot! I did some similar research, though, and I was confused. It seemed to me that test on rats was Olney's original research, and my understanding of the chronology seems to be that those tests on rats were the ones that Olney discredited. My reasoning for this was that Erowid is a pretty old site and their report on Olney's legions seems older than all of the references to Olney discrediting his original research (these all seem to be very recent.) Maybe I wasn't careful in reading Erowid, but I'd still like to find some more conclusive chronology. Jolb 22:30, 14 September 2006 (UTC)

I jumped the gun and did some research of my own. You can read what I found (with sources) on the article page. Jolb 23:00, 14 September 2006 (UTC)

Major Improvement

I think this is a significant improvement in the page. I feel that we've created a concise and objective resource about Olney's Lesions. Thanks, Valoem!

np anytime =D Valoem ^talk 03:04, 15 September 2006 (UTC)

Psychedelic

Your substitution of "serotonergic" for "psychedelic" isn't correct. For one, according to Psychoactive drug, THC is a psychedelic, and it does NOT act on the Serotonin systems. Secondly, I'm having a debate with Thoric, the creator of the diagram on that page, on Thoric's talk page about whether that the term "psychedelic" includes dissociatives like DXM and ketamine, the very drugs that DO cause Olney's lesions. Therefore, I'll change the title back. Otherwise, I like that edit.Jolb 03:25, 30 January 2007 (UTC)

About the Carliss Article

Hey, I reverted your edit because that Carliss article is already referenced in the text:

However, oral administration of dextromethorphan does not cause vacuolization in rats' brains.[5]

More importantly, that study was particularly about ORAL administration of DXM, (making it more relevant for humans since they usually take DXM orally) which you left out of your edit. Jolb 23:45, 26 October 2007 (UTC)

Olney's life

Olney himself is now dying of amyotrophic lateral sclerosis, so whatever he might have been doing in his personal life to avoid neuronal degeneration and death didn't work very well. —Preceding unsigned comment added by 75.15.137.89 (talk) 17:36, 9 May 2008 (UTC)

Whoops, wrong Dr Olney. My mistake. 75.15.137.89 (talk) 17:39, 9 May 2008 (UTC)

Effects of the lesions

Maybe I just overlooked something, but while the article currently contains a nice amount of information on how and why Olney's lesions develop it seems that it doesn't really explain what effects (on behavior and otherwise) these lesions actually produced in the lab mice. If there are any such effects, other than the increased mortality, it would be nice if someone could include the information in the article. Thanks. --84.186.245.124 (talk) 22:36, 23 October 2008 (UTC)

Exactly -- most people who visit this page are researching the symptoms of the lesions. What are they? —Preceding unsigned comment added by 24.68.208.220 (talk) 16:56, 19 September 2010 (UTC)

As the translation goes on..

Now I'm translating this article for the RuWiki. One note to check out: age-dependent change in the structure of NMDAR might underlie the increased mortality in the old rats (there's a "developmental change" in NR subunits composition). --CopperKettle (talk) 20:43, 3 December 2008 (UTC)

Another bit:

No tests have been conducted to test the validity of post-dissociative development of vacuolization in human brain cells

- as I understand, vacuoles are emerging in the tissue, not in the cells themselves. --CopperKettle (talk) 21:17, 3 December 2008 (UTC)

Another one "William White, a DXM researcher". I have questions: Did he conduct any basic research? PubMed doesn't seem to find any links to the query "White W Dextromethorphan". Did he had any neuroscientific or biological degree? --CopperKettle (talk) 22:00, 3 December 2008 (UTC)

How about exchanging the "researcher" title into the less misleading "amateur experimenter" or the "self-taught experimenter", "an experimenter without a degree in biology" etc.? I'll wait a couple of days for the answer and then I'll be bold and change it. --CopperKettle (talk) 12:38, 4 December 2008 (UTC)

Here I've found a link to W.White's email, bwhite@oucsace.cs.ohiou.edu - in the .edu domain, a university, but dated back to 1996. Hmm.. --CopperKettle (talk) 12:56, 4 December 2008 (UTC)

Maybe he was a student? I'd suggest calling W. White just a writer at this point.Shubi (talk) 17:52, 24 January 2009 (UTC)

I would say that he did research because the FAQ itself was an original synthesis of information from peer-reviewed scientific literature and from information on the subjective effects of DXM that he received from numerous (hundreds, I believe) of users. The last time I had any correspondence with Will White, about 5 years ago, he was continuing to pursue a PhD in neurobiology or some related field (all I know is that it had something to do with modelling neuronal systems with partial differential equations). I don't think calling him a "DXM researcher" gives him undue credit, but it probably would not be how he described himself. I think he should just be referred to as the author of the FAQ, because he certainly didn't have a career researching DXM, even though he did spend a lot of time researching DXM for the FAQ. AlkaloidMan (talk) 04:22, 24 October 2010 (UTC)AlkaloidMan

Nitrous oxide

So of all the NMDA receptor antagonists, nitrous oxide is the only one to cause olney lesions that are reversible...correct? Meaning it is the least damaging, the least likely to cause olney's lesions, and definitely the safest of the them, correct? And the olney's lesions cause by others such as pcp, dxm, and ketamine aren't reversible right? Or less reversible. Zachorious (talk) 23:35, 17 February 2009 (UTC)

It's my understanding that "minor" lesions are reversible. Given the rapid elimination of nitrous, it stands to reason that it would tend to produce very minor lesions. But there is no definitive answer to my knowledge. 70.153.234.155 (talk) 03:54, 19 April 2009 (UTC)

Do neither of you have a copy of Olney's 1989 paper? Here's a quote from it:

A time course study by light microscopy revealed that the vacuoles were detectable 2 hours after a single exposure to MK-801 (1.0 mg/kg sc) and became increasingly more conspicuous at 4, 8, and 12 hours. However, in the interval from 18 to 24 hours, the reaction subsided and the morphology of most neurons, as evaluated by light microscopy, appeared to have returned to normal."

Regarding repeated doses: "When rats were treated daily with MK-801 for 4 days with higher or more steeply increasing dose schedules (0.25, 0.5, 0.75, and 1.0, or 0.25, 0.5, 1.0, and 2.0 mg/kg sc on days 1, 2, 3 and 4, respectively) and the brains were examined 4 hours after the treatment on day 4, these brains displayd the typical cytopathological changes that would be expected 4 hours after a single treatment, but there was no evidence (by light microscopy) of a cumulative effect or of the reaction progressing to an irreversible stage." Read that last part again. I don't know where you're getting this idea that Olney's lesions are "irreversible" but it's pretty clear if you read the original document that the lesions reverse themselves with 24 to 48 horus. Near the end of the paper: "Vacuolization in response to PCP or MK-801 becomes increasingly severe in the first 12 hours and then gradually diminishes in the next 12 hours; repeated treatment does not result in cumulative effects." The paper even goes on to suggest that the cells appear to become "tolerant" to NMDA antagonist neurotoxicity. In fact, the ending of the article is very positive and says that NMDA antagonists are also known to have neuroprotective properties and that even if someone has to take one of these drugs to protect from brain damage due to stroke, for example, it seems like a fair trade off to only have a temporary psychosis. That is, it's quite obvious that Olney found no evidence that these neurotoxic changes were permanent and even saw no reason to be concerned about repeated dosing. Reference: Olney JW, Labruyere J, Price MT. (1989) Pathological Changes Induced in Cerebrocortical Neurons by Phencyclidine and Related Drugs. Science. 244: 1360 - 1362. AlkaloidMan (talk) 04:37, 24 October 2010 (UTC)AlkaloidMan

Please make sure to actually read papers before citing them

"These vacuoles lead to a concentration of microglia and Heat-Shock Protein 70 (Hsp70), which formed irreversible lesions. The dissociatives also seemed to form antecedents of other forms of brain damage in the test subjects." The reference given at the end is for Olney et al. (1989). I have a copy of the paper. It's only 3 pages long. It says absolutely NOTHING about Hsp70. It says absolutely nothing about these neurotoxic changes or vacuolation being irreversible. To the contrary, the paper makes it clear the the affected cells appear to return to normal after 24 to 48 hours. Repeated doses with NMDA antagonists did not lead to a cumulative effect, leading the authors to hypothesize that cells became "tolerant" to the effect of repeated NMDA antagonist exposure. To attribute the statement: "dissociatives also seemed to form antecedents to other forms of brain damage in the test subjects" to Olney et al. (1989) is inaccurate. It's looks to me like I can be essentially certain that whoever cited Olney et al. (1989) for the last sentence (or the first whole paragraph) has not ever read the paper. Please make sure that you actually read a paper before citing it as a source of information. The stuff here is completely inaccurate. Olney JW, Labruyere J, Price MT. (1989) Pathological Changes Induced in Cerebrocortical Neurons by Phencyclidine and Related Drugs. Science. 244: 1360 - 1362. AlkaloidMan (talk) 04:48, 24 October 2010 (UTC)AlkaloidMan

Zombie Effects

This drug will put into a non-coherantstate with super human strenghth. Will cause great depression and suicidal thoughts.Highly addictive. — Preceding unsigned comment added by 74.99.173.166 (talk) 04:22, 2 October 2012 (UTC)

Huh? What drug? What are you talking about? 24.46.248.161 (talk) 20:54, 1 May 2013 (UTC)

Remove White's opinion

I would like to remove the last sentence in the Controversy section for two reasons: 1. William E. White is a dubious person which cannot be related to any expert on the field 2. The statement is outdated, recent research shows evidence for Olney's lesions in humans. See my addition in the history section.

If no one objects for good reason I will remove the sentence "White therefore concluded that based on some fundamental differences between rat biology and human biology and because there have only been very few studies done on the occurrence of Olney's lesions, no connection can currently be proved or disproved" in a few days. LuxMaryn (talk) 01:25, 28 February 2016 (UTC)

Intro section sites exactly one source and mostly just gives opinion-based non-cited information

The intro section needs to be completely rewritten to cite actual sources, not provide someone's useless opinion. — Preceding unsigned comment added by Orangesherbet0 (talk • contribs) 06:44, 5 November 2019 (UTC)

Does the "NMDA receptor antagonist neurotoxicity and psychotomimetic activity" exist?

I can't find the article "NMDA receptor antagonist neurotoxicity and psychotomimetic activity" anywhere, and the contents seem kinda important for the article, as it's our only source that GABA modulators also get administered with NMDA antagonist anesthetics.

• PubMed only has the abstract, and I'm not sure if the bibliographic data is right.
• Google Scholar has 3 versions of the article, but they're all abstracting services like PubMed.
• It took a little digging, but Wiley has an archive of Anesthesia, an English-language journal published monthly by the Japanese Association for Anesthesiology. "Masui" [麻酔] is Japanese for Anesthesia, and Googling the original hiragana pulls up the JAA in a Japanese-language page that (via Google Translate) says it's an English-language journal published monthly, so I think this is it.
• The article doesn't appear in issue 52 of that archive, and in fact there is no article published with that author list anywhere in the journal. I haven't tried looking for all possible subsets of the authors, but the first author has only published two articles there, and none of the PI's 62 hits seem relevant.
• The PI's name romanizes to Shingu Koh, and I tried Googling around for his homepage at Kansai Medical University to see if he posted a link to it. But I'm neither sure if he has a homepage, nor that, if it exists, I could find it without the original katakana. (I tried guessing with a romanization table, but no luck.)
• Presumably the IP who added it had access to the article, but they haven't edited under that address since 2007, and it's hard to find an IP user anyways.

Do you, dear reader, know where to find a copy? Bernanke's Crossbow (talk) 02:46, 19 June 2023 (UTC)