Psycho-Babble Medication Thread 383476

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thanks, larry, for the refs (nm) » Larry Hoover

Posted by chemist on August 29, 2004, at 20:38:13

In reply to Re: Ecstasy safely converted and prescribed? » verne, posted by Larry Hoover on August 29, 2004, at 20:31:34

 

Re: to all... » flmm

Posted by Larry Hoover on August 29, 2004, at 21:09:25

In reply to Re: to all..., posted by flmm on August 29, 2004, at 18:46:09

> There is an implication that used correctly, MDMA possibly is safe, according to your post. I believe this is not the case and feel it is reckless to imply this.

Well, your position probably arises from a much-publicized paper in the prestigious journal Science, which was later subject to a much less-publicized full retraction. The study had used the wrong drug! The primates had received no MDMA at all! See the first abstract, along with a link I've added, which gives the full-text of the retraction.

Also, that prestigious researcher, Ricaurte, later gave MDMA to monkeys for eighteen months, as much as they wanted. Following two months of withdrawal, there was no change in brain neurotransmitter levels from normal levels. "Further, there were no measurable decrements in serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) or VMAT in any brain regions assayed."

There goes another myth.

Lar


Science. 2002 Sep 27;297(5590):2260-3.

Retraction in:
Ricaurte GA, Yuan J, Hatzidimitriou G, Cord BJ, McCann UD. Science. 2003 Sep 12;301(5639):1479.
See:http://mdma.net/toxicity/retracted.html

Comment in:
Science. 2002 Sep 27;297(5590):2185-7.
Science. 2003 Jun 6;300(5625):1504-5; author reply 1504-5.

Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA ("ecstasy").

Ricaurte GA, Yuan J, Hatzidimitriou G, Cord BJ, McCann UD.

Department of Neurology, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. Ricaurte@jhmi.edu

The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or "ecstasy") is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.


Neuropsychopharmacology. 2004 Jul;29(7):1270-81.

Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys.

Fantegrossi WE, Woolverton WL, Kilbourn M, Sherman P, Yuan J, Hatzidimitriou G, Ricaurte GA, Woods JH, Winger G.

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48101-0632, USA. billfan@umich.edu

The effects of self-administered 3,4-methylenedioxymethamphetamine (MDMA) on behavior and neurochemistry have not been previously studied in laboratory primates. We investigated the capacity of MDMA and its enantiomers to maintain contingent responding over an extended duration, whether any decrements in the reinforcing effects of these compounds would be observed over time, whether such decrements would be MDMA-selective, and whether any neurochemical correlates could be identified. Animals were previously trained to self-administer cocaine, then exposed to periodic substitutions of various doses of racemic MDMA and its enantiomers; full dose-effect curves were generated for each MDMA compound repeatedly over the duration of the study. After approximately 18 months of MDMA self-administration, drug exposure was halted and after at least 2 months drug abstinence, animals were scanned using positron emission tomography (PET) with the vesicular monoamine transporter (VMAT) ligand dihydrotetrabenazine (DTBZ). Shortly thereafter, animals were euthanized, brains were dissected, and samples were assayed for brain monoamines and their metabolites using high-performance liquid chromatography (HPLC), and for VMAT using DTBZ binding. The reinforcing effects of racemic and R(-)-MDMA were reduced over a long series (months) of individual self-administration access periods; the reinforcing effects of S+-MDMA were more resistant to this effect, but were attenuated for one animal. The reinforcing effects of cocaine were not altered by chronic MDMA self-administration, nor was the VMAT binding potential as assessed by PET. Further, there were no measurable decrements in serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) or VMAT in any brain regions assayed. The reinforcing effects of MDMA are selectively attenuated by chronic MDMA self-administration, although this behavioral change appears to occur in the absence of any frank neurochemical correlates of toxicity. Copyright 2004 Nature Publishing Group

 

Re: to all... » Larry Hoover

Posted by chemist on August 29, 2004, at 21:20:00

In reply to Re: to all... » flmm, posted by Larry Hoover on August 29, 2004, at 21:09:25

hello there, chemist here....as a bonus to larry's post - and given that other contributions to this thread have been ill- or non-informed, and hence i suspect that further investigation will not be persued with vigor - i'll take the liberty of spoiling the surprise in re: the Science pub of last september: the drug administered to the primates was in fact pharmaceutical-grade methamphetamine. oops. all the best, chemist


> > There is an implication that used correctly, MDMA possibly is safe, according to your post. I believe this is not the case and feel it is reckless to imply this.
>
> Well, your position probably arises from a much-publicized paper in the prestigious journal Science, which was later subject to a much less-publicized full retraction. The study had used the wrong drug! The primates had received no MDMA at all! See the first abstract, along with a link I've added, which gives the full-text of the retraction.
>
> Also, that prestigious researcher, Ricaurte, later gave MDMA to monkeys for eighteen months, as much as they wanted. Following two months of withdrawal, there was no change in brain neurotransmitter levels from normal levels. "Further, there were no measurable decrements in serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) or VMAT in any brain regions assayed."
>
> There goes another myth.
>
> Lar
>
>
> Science. 2002 Sep 27;297(5590):2260-3.
>
> Retraction in:
> Ricaurte GA, Yuan J, Hatzidimitriou G, Cord BJ, McCann UD. Science. 2003 Sep 12;301(5639):1479.
> See:http://mdma.net/toxicity/retracted.html
>
> Comment in:
> Science. 2002 Sep 27;297(5590):2185-7.
> Science. 2003 Jun 6;300(5625):1504-5; author reply 1504-5.
>
> Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA ("ecstasy").
>
> Ricaurte GA, Yuan J, Hatzidimitriou G, Cord BJ, McCann UD.
>
> Department of Neurology, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. Ricaurte@jhmi.edu
>
> The prevailing view is that the popular recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, or "ecstasy") is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic neurotoxicity. MDMA neurotoxicity was associated with increased vulnerability to motor dysfunction secondary to dopamine depletion. These results have implications for mechanisms of MDMA neurotoxicity and suggest that recreational MDMA users may unwittingly be putting themselves at risk, either as young adults or later in life, for developing neuropsychiatric disorders related to brain dopamine and/or serotonin deficiency.
>
>
> Neuropsychopharmacology. 2004 Jul;29(7):1270-81.
>
> Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys.
>
> Fantegrossi WE, Woolverton WL, Kilbourn M, Sherman P, Yuan J, Hatzidimitriou G, Ricaurte GA, Woods JH, Winger G.
>
> Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48101-0632, USA. billfan@umich.edu
>
> The effects of self-administered 3,4-methylenedioxymethamphetamine (MDMA) on behavior and neurochemistry have not been previously studied in laboratory primates. We investigated the capacity of MDMA and its enantiomers to maintain contingent responding over an extended duration, whether any decrements in the reinforcing effects of these compounds would be observed over time, whether such decrements would be MDMA-selective, and whether any neurochemical correlates could be identified. Animals were previously trained to self-administer cocaine, then exposed to periodic substitutions of various doses of racemic MDMA and its enantiomers; full dose-effect curves were generated for each MDMA compound repeatedly over the duration of the study. After approximately 18 months of MDMA self-administration, drug exposure was halted and after at least 2 months drug abstinence, animals were scanned using positron emission tomography (PET) with the vesicular monoamine transporter (VMAT) ligand dihydrotetrabenazine (DTBZ). Shortly thereafter, animals were euthanized, brains were dissected, and samples were assayed for brain monoamines and their metabolites using high-performance liquid chromatography (HPLC), and for VMAT using DTBZ binding. The reinforcing effects of racemic and R(-)-MDMA were reduced over a long series (months) of individual self-administration access periods; the reinforcing effects of S+-MDMA were more resistant to this effect, but were attenuated for one animal. The reinforcing effects of cocaine were not altered by chronic MDMA self-administration, nor was the VMAT binding potential as assessed by PET. Further, there were no measurable decrements in serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) or VMAT in any brain regions assayed. The reinforcing effects of MDMA are selectively attenuated by chronic MDMA self-administration, although this behavioral change appears to occur in the absence of any frank neurochemical correlates of toxicity. Copyright 2004 Nature Publishing Group
>
>
>
>

 

oops, i meant Sept. 2002.... (nm) » chemist

Posted by chemist on August 29, 2004, at 21:21:52

In reply to Re: to all... » Larry Hoover, posted by chemist on August 29, 2004, at 21:20:00

 

Re: to all...

Posted by verne on August 29, 2004, at 21:52:52

In reply to Re: to all... » Larry Hoover, posted by chemist on August 29, 2004, at 21:20:00

Hoover and the Chemist have quite the "tag team" act on this board. I've seen this routine used on other boards in an attempt to bully and silence other posters. One supports the other as they gang up on any perceived opposition.

What purpose, for example, does one of their comments, "given that other contributions to this thread have been ill- or non-informed" serve? Let each reader decide for themselves how informed a post is.

Sadly,this sort of tag-team bullying is usually successful. Many posters, often hurting, in need of help and real answers, instead are drowned out unless they have sufficient references and meet the chemists' level of proof. Worn down, they leave.

And in the end, the chemists prevail - at least, in their own minds.

 

Re: to all... » verne

Posted by Larry Hoover on August 29, 2004, at 22:08:07

In reply to Re: to all..., posted by verne on August 29, 2004, at 21:52:52

> Hoover and the Chemist have quite the "tag team" act on this board. I've seen this routine used on other boards in an attempt to bully and silence other posters. One supports the other as they gang up on any perceived opposition.

I speak up when misinformation is being given. I'm a toxicologist. I study this sort of thing both vocationally and avocationally. I read it as part of my job, and I read it for fun.

I'm not trying to bully or silence anybody. I'm trying to inform. I think I'm a decent judge of quality information, but please feel free to disagree, or post a dissenting position.

I don't know that chemist and I have joined our voices together on a single issue before this time, so I cannot say it is either a pattern, nor a planned act. I had the references available to me, to back up the simpler statements he had made. I'd be happy to back you up, too, if the opportunity arises.

Lar

 

Re: to all... chemist

Posted by flmm on August 29, 2004, at 22:17:36

In reply to Re: to all..., posted by verne on August 29, 2004, at 21:52:52

oh great chemist, flmm here!
You remind me of the many shrinks I have seen in my life who say things like.."it should not do that", or "I don't think it caused that, must have been something else!" How very patronizing of you to include my "limited knowledge" quote! Oh well, we all can't be the all knowing "Chemist" Well you can take all your knowledge and it does not add up to a hill of beans in the real world. I know more about meds than my shrink does and he has a degree, what he lacks is street smarts. You may have issues here as well. Regardless, I think your advice is of very little value and probably can get some people hurt if they listen to you. Sorry if I don't consider you the "Genius" of chemistry that you are in your own mind. For now i will get my advice elsewhere, but thanks anyways, oh great "CHEMIST"

 

Re: to all... chemist

Posted by flmm on August 29, 2004, at 22:21:44

In reply to Re: to all... chemist, posted by flmm on August 29, 2004, at 22:17:36

By the way, I speak from experience when it comes to E and what it can do top your loved ones! Great advice "CHEMIST"

 

i am confused... » verne

Posted by chemist on August 29, 2004, at 22:33:34

In reply to Re: to all..., posted by verne on August 29, 2004, at 21:52:52

hello there, chemist here....my comments below, delineated by asterisks....all the best, chemist


> Hoover and the Chemist have quite the "tag team" act on this board. I've seen this routine used on other boards in an attempt to bully and silence other posters. One supports the other as they gang up on any perceived opposition.

*** this statement is untrue, and unless you have archived URLs for threads that show the contrary - and i cannot recall a single event - i stand firm in this regard. either produce the evidence that Larry Hoover and myself act as you assert, or retract your assertion. the burden of proof is on you. please supply it. ***
>
> What purpose, for example, does one of their comments, "given that other contributions to this thread have been ill- or non-informed" serve? Let each reader decide for themselves how informed a post is.

*** i ask, what purpose do blanket statements that are in fact untrue serve, especially when the people making them cannot and/or do not provide evidence that their assertions are true? this falls under the category of ill-informed and/or non-informed. i repeatedly asked for peer-reviewed information supporting various claims, and none was provided. if you have some, by all means, support your claims. until then, your assertions are opinions not founded in fact nor supported by objective evidence. period. ***
>
> Sadly,this sort of tag-team bullying is usually successful. Many posters, often hurting, in need of help and real answers, instead are drowned out unless they have sufficient references and meet the chemists' level of proof. Worn down, they leave.

*** again, please provide evidence that i - chemist - have been the sole cause of any person leaving the psycho-babble community. the reason i ask for references (and my willingness to provide or make clear that i am not informed in many cases) from posters who make grandiose statements that are all-encompassing is that such sweeping arguments need to be supported.. ***
>
> And in the end, the chemists prevail - at least, in their own minds.
>
>
*** i hold a doctorate in chemistry, and have been a post-doctoral fellow/lecturer at 2 medical schools and a top-ten university. i have published in the esteemed journal Science (my 10th publication). i have held a position as an assistant professor of chemistry, have collaborated in the past and present with a molecular design group at a privately-held pharma, and currently lecture in the 13th-ranked chemistry/biochemistry department in the nation, for whatever good the u.s. news and world report rankings do us. larry hoover is at least as educated as i am and, further, knows more about the stuff on this and other boards than i do. i am a chemist, and like larry, it is the way i pay the bills. it is also my passion. i look forward to your response. ***

 

Re: Ecstasy safely converted and prescribed? chem

Posted by flmm on August 29, 2004, at 22:33:45

In reply to Re: Ecstasy safely converted and prescribed? » verne, posted by chemist on August 29, 2004, at 20:07:25

Chemist, maybe you should get a girlfriend or something and stop reading all these books on drugs. Get a life man! If you want to take E and burn up, knock yourself out man. Use your brain "GENIUS"

 

Re: Ecstasy safely converted and prescribed? chem

Posted by flmm on August 29, 2004, at 22:40:08

In reply to Re: Ecstasy safely converted and prescribed? chem, posted by flmm on August 29, 2004, at 22:33:45

Man I have never read a more insecure post than your last "chemist". Ok, ok you are the all knowing chemist, there is no other! No one knows more than you. Do ya feel better buddy! Good, now put down your book, and go get laid buddy. Then we will all feel better!

 

Re: i am confused... err chemist

Posted by flmm on August 29, 2004, at 22:43:00

In reply to i am confused... » verne, posted by chemist on August 29, 2004, at 22:33:34

Oops, sorry chemist, I missed where you stated 13th ranked. I guess you are not the greatest "Chemist" after all. My apologies.......

 

Re: Ecstasy safely converted and prescribed? chem » flmm

Posted by chemist on August 29, 2004, at 22:43:52

In reply to Re: Ecstasy safely converted and prescribed? chem, posted by flmm on August 29, 2004, at 22:33:45

> Chemist, maybe you should get a girlfriend or something and stop reading all these books on drugs. Get a life man! If you want to take E and burn up, knock yourself out man. Use your brain "GENIUS"


hello there, chemist here...your remarks are offensive and incorrect. there is really no other way to comment on your last posts, and it is the most civil way i can quantify your personal attacks on me. all the best, chemist

 

Re: Ecstasy safely converted and prescribed? chem

Posted by flmm on August 29, 2004, at 22:49:16

In reply to Re: Ecstasy safely converted and prescribed? chem » flmm, posted by chemist on August 29, 2004, at 22:43:52

Sorry to offend good buddy, but there is nothing more offensive than your passive-agressive," I am a genius and you are an idiot," stance, that you so slyly put in all your posts. You can read every book you want but you still have a problem with real world logic. Most guys like you do. That's why you must defend your knowledge so strongly. It stems from insecurity.

 

Re: Ecstasy safely converted and prescribed? chem

Posted by flmm on August 29, 2004, at 22:53:46

In reply to Re: Ecstasy safely converted and prescribed? chem, posted by flmm on August 29, 2004, at 22:40:08

I am out Chemist, Peace good buddy, just playin.....

 

are you sure? » flmm

Posted by chemist on August 29, 2004, at 22:56:09

In reply to Re: Ecstasy safely converted and prescribed? chem, posted by flmm on August 29, 2004, at 22:49:16

> Sorry to offend good buddy, but there is nothing more offensive than your passive-agressive," I am a genius and you are an idiot," stance, that you so slyly put in all your posts. You can read every book you want but you still have a problem with real world logic. Most guys like you do. That's why you must defend your knowledge so strongly. It stems from insecurity.


hello there, chemist here...are you certain that the quote you assert i place in ``every post'' does in fact appear? i was not aware of this...thank you for bringing it to my attention...all the best, chemist

 

backpedalling? » flmm

Posted by chemist on August 29, 2004, at 22:57:59

In reply to Re: Ecstasy safely converted and prescribed? chem, posted by flmm on August 29, 2004, at 22:53:46

> I am out Chemist, Peace good buddy, just playin.....


hello there, chemist here...i have little to no reason to believe that you were just playing....all the best, chemist

 

Re: backpedalling?

Posted by flmm on August 29, 2004, at 23:14:11

In reply to backpedalling? » flmm, posted by chemist on August 29, 2004, at 22:57:59

You are right oh great Chemist. Playing, no. Having fun yes! It will probably get me kicked off but you know what? It was worth it! You don't know squat! You should eat some food or vitamins or meds that will help you with your self esteem. You can still be the old, great chemist that you were. Maybe some people will even listen to you! Just not me, I have lost all respect for the great chemist and long for the old days, when I could trust what I heard. After your outburst, citing your outstanding credentials, I prefer to get my advice from someone with more confidence!

 

Re: backpedalling?

Posted by gardenergirl on August 29, 2004, at 23:36:36

In reply to Re: backpedalling?, posted by flmm on August 29, 2004, at 23:14:11

The dude/dudette doth protest too much, methinks.

gg (thanks be to Shakespeare)

 

Re: please be civil » chemist » verne » flmm

Posted by Dr. Bob on August 29, 2004, at 23:40:47

In reply to Re: to all... chemist, posted by flmm on August 29, 2004, at 22:17:36

> i agree with your subjective assessment of your knowledge of the subject being discussed in this thread - limited - and applaud the depth of your self-realization.
>
> chemist

> I've seen this routine used on other boards in an attempt to bully and silence other posters.
>
> verne

> How very patronizing of you to include my "limited knowledge" quote! Oh well, we all can't be the all knowing "Chemist" Well you can take all your knowledge and it does not add up to a hill of beans in the real world... I think your advice is of very little value...
>
> flmm

Please don't be sarcastic, jump to conclusions about others, or post anything that could lead them to feel accused or put down.

Sharing something about your own issues and their possible role in your reaction might be an interesting exercise -- and might help others respond to you supportively.

If you or anyone else has questions about this or about posting policies in general, or is interested in alternative ways of expressing oneself, please see the FAQ:

http://www.dr-bob.org/babble/faq.html#civil

Also, follow-ups regarding these issues should be redirected to Psycho-Babble Administration.

Thanks,

Bob

 

Re: Ecstasy safely converted and prescribed?

Posted by Larry Hoover on August 31, 2004, at 7:34:02

In reply to Re: Ecstasy safely converted and prescribed?, posted by linkadge on August 29, 2004, at 11:16:53

I'd like to take this opportunity to provide a more in-depth analysis of my position vis a vis therapeutic use of MDMA.

I can best represent my feelings by discussing another drug first. If I knew of an individual dying of bone cancer (a horrible painful exit from this mortal coil), I would hope they would be prescribed a suitable pain control medication. Perhaps, I should say, *the* suitable pain control medication, heroin. For these individuals, there is no psychotropic effect. Their powerfully up-regulated mu-opioid system (from the pain stimulus) mops up the heroin first, as those nociceptive receptors have a higher affinity for the drug than do the psychotropic ones. Unfortunately, too many doctors have images of junkies and shooting galleries in their minds, and heroin is far too seldom put to this admirable use. I have heard remarkable tales of people coming back to their old selves, under the influence of the heroin, and being permitted a last and fruitful interaction with their loved ones, prior to their inevitable death. Yet, I have actually heard doctors say that they don't want to turn the sufferer into an addict, and refuse the prescription outright. As if that mattered, in that context. But, in fact, the pain itself precludes addiction (if the dose is appropriate), as addiction can only follow psychotropic effects. So even that argument is fallacious. It is a classic non sequitur, and it arises from social propaganda. Drug abuse is a property of people, not of the drug itself.

Now, with respect to MDMA. There is a similar therapeutic use of MDMA, in an appropriately selected population (e.g. sufferers of PTSD), who are psychologically prepared for the drug experience, and guided by skilled clinicians. Two of the distinctive characteristics of this process (and of the use of heroin, as above), are that the drug is supplied in a much purer form than can be obtained "on the street", and at a very precise dose. You don't know what you're getting from a street dealer, or the dose, nor can you readily obtain that information. For example, an early batch of street MDMA was contaminated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), in an attempt to adulterate the MDMA with the drug meperidine (Demerol). Unfortunately for a few individuals, the MPTP was present in high enough concentrations to induce permanent Parkinson's-like symptoms. That's the problem with what we call "bucket chemists". Anybody can get a recipe off the Internet, but that doesn't turn you into a chemist....no more so than reading a recipe for duck a l'orange will turn you into a cook.

I'm not a lily-white ivory-tower demagogue. I was a hard-core addict for many years. I did more PCP than I have a right to have even survived. I know what drug abuse is. And, if I may be so bold, I know what drug abuse isn't.

One hundred years ago, Eaton's (the Canadian equivalent to Sears) sold tincture of opium, and hemp extract. The latter was for "female concerns", or something phrased similar. Lo and behold, one hundred years later, we discover that PMS and dysmennorhea may be related to cyclic depletion of endocannibinoids (our internal, natural cannabis-like chemicals). That's not to suggest that pot-smoking is always valid, but it also does not invalidate medical use of marijuana. Or of opium.

Alcohol is an excellent disinfectant, and used in moderation, reduces the risk of heart attack.... Need I go on?

Lar

 

Redirect: administrative issues

Posted by Dr. Bob on August 31, 2004, at 7:35:35

In reply to Re: please be civil » chemist » verne » flmm, posted by Dr. Bob on August 29, 2004, at 23:40:47

> follow-ups regarding these issues should be redirected to Psycho-Babble Administration.

Here's a link:

http://www.dr-bob.org/babble/admin/20040717/msgs/384533.html

Thanks,

Bob

 

Re: Ecstasy safely converted and prescribed? » Larry Hoover

Posted by Dave001 on August 31, 2004, at 8:56:43

In reply to Re: Ecstasy safely converted and prescribed? » verne, posted by Larry Hoover on August 29, 2004, at 20:31:34

<snip>

---- begin quote ----
> The first abstract below demonstrates this relationship nicely. Note that the threshold for brain damage, or even abnormal brain chemistry post-use, is greater than 4 mg/kg (by interperitoneal injection, not oral), a dose three times the typical human dose, employing a route of intake not normally employed by humans. Only
----- end quote -----

The study you're quoting involves rats. You can't directly compare animal doses to human doses without first calculating the human equivalent dose (HED) which takes into account such things as body surface area. To get the HED for rats you should multiply the dose above by 0.16. So 4 mg/kg * 0.16 = 0.64 mg/kg. That's a total dose of only 38.4 mg in your 60 kg human. Repeated dosing of MDMA and amphetamines gets even more complicated because rats metabolize the drug so much faster than humans.

Dave

<snip>

 

Re: Ecstasy safely converted and prescribed? » Dave001

Posted by Larry Hoover on August 31, 2004, at 9:19:46

In reply to Re: Ecstasy safely converted and prescribed? » Larry Hoover, posted by Dave001 on August 31, 2004, at 8:56:43

> <snip>
>
> ---- begin quote ----
> > The first abstract below demonstrates this relationship nicely. Note that the threshold for brain damage, or even abnormal brain chemistry post-use, is greater than 4 mg/kg (by interperitoneal injection, not oral), a dose three times the typical human dose, employing a route of intake not normally employed by humans. Only
> ----- end quote -----
>
> The study you're quoting involves rats. You can't directly compare animal doses to human doses without first calculating the human equivalent dose (HED) which takes into account such things as body surface area. To get the HED for rats you should multiply the dose above by 0.16. So 4 mg/kg * 0.16 = 0.64 mg/kg. That's a total dose of only 38.4 mg in your 60 kg human. Repeated dosing of MDMA and amphetamines gets even more complicated because rats metabolize the drug so much faster than humans.
>
> Dave
>
> <snip>

I appreciate the digression into uncertainties of estimate. There are always assumptions made in cross-species comparisons, of course. There are also different ways to estimate HED (I assume yours is BW to the 2/3 power, rather than the metabolic parameter BW to the 3/4). Primate studies are probably more applicable, and the same pattern is found as in the rats. I.e. only extremely high doses, or recurrent use without sufficient recovery time, lead to measurable neuronal damage or changes in neurotransmitter concentrations. Another variable to consider is antioxidant status, and I wonder if e.g. ravers aren't a little more likely to eat poorly?

By no means was I suggesting the referenced article was conclusive, but merely suggestive. There is a toxic threshold, and the issue of exceeding that threshold is not clearly defined in humans.

Lar

 

Re: Ecstasy safely converted and prescribed? » Larry Hoover

Posted by Dave001 on August 31, 2004, at 10:29:18

In reply to Re: Ecstasy safely converted and prescribed? » Dave001, posted by Larry Hoover on August 31, 2004, at 9:19:46

> > <snip>
> >
> > ---- begin quote ----
> > > The first abstract below demonstrates this relationship nicely. Note that the threshold for brain damage, or even abnormal brain chemistry post-use, is greater than 4 mg/kg (by interperitoneal injection, not oral), a dose three times the typical human dose, employing a route of intake not normally employed by humans. Only
> > ----- end quote -----
> >
> > The study you're quoting involves rats. You can't directly compare animal doses to human doses without first calculating the human equivalent dose (HED) which takes into account such things as body surface area. To get the HED for rats you should multiply the dose above by 0.16. So 4 mg/kg * 0.16 = 0.64 mg/kg. That's a total dose of only 38.4 mg in your 60 kg human. Repeated dosing of MDMA and amphetamines gets even more complicated because rats metabolize the drug so much faster than humans.
> >
> > Dave
> >
> > <snip>
>
> I appreciate the digression into uncertainties of estimate. There are always assumptions made in cross-species comparisons, of course. There are

And thus the need to correct false assumptions, such as a 1:1 association with human metabolic rate. ;-)

> also different ways to estimate HED (I assume yours is BW to the 2/3 power, rather than the metabolic parameter BW to the 3/4). Primate

It is generally preferable to use standardized conversion factors which have demonstrated reasonable accuracy. Using generic formulas is usually is only advisable if the species is not listed or if the weight falls outside of the specified ranges. These are the methods used by drug companies when extrapolating from animal data to determine initial human doses.

> studies are probably more applicable, and the same pattern is found as in the rats. I.e. only extremely high doses, or recurrent use without sufficient recovery time, lead to measurable neuronal damage or changes in neurotransmitter concentrations. Another variable to consider is antioxidant status, and I wonder if e.g. ravers aren't a little more likely to eat poorly?
>

Quite possibly. I would imagine the body naturally kicks the production of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase, etc., into full gear in the presence of such toxins.

> By no means was I suggesting the referenced article was conclusive, but merely suggestive. There is a toxic threshold, and the issue of exceeding that threshold is not clearly defined in humans.

My comments were not intended to make any inference regarding the toxicity of MDMA.

Dave


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