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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 13 to 37 of 45. Go back in thread:
Posted by West on August 10, 2008, at 10:46:48
In reply to Re: Freud, Cocaine, and Adderall » West, posted by llurpsienoodle on August 10, 2008, at 10:20:49
sorry, garden centre then.
Posted by SLS on August 10, 2008, at 10:55:38
In reply to Re: Freud, Cocaine, and Adderall, posted by West on August 10, 2008, at 10:44:31
> If you think they remain harmless i suggest you research the matter.
The onus of proof is on you for having made the statement in the first place.
> They damage your brain damage and interfere with your mood, this is not opinion but fact.
Opinions for which you will not substantiate as fact?
> As far as i'm concerned it's not a subject for which there exists any ground for debate.
Then why bring it up?
- Scott
Posted by llurpsienoodle on August 10, 2008, at 11:03:53
In reply to Re: Freud, Cocaine, and Adderall » West, posted by SLS on August 10, 2008, at 10:55:38
> > If you think they remain harmless i suggest you research the matter.
>
> The onus of proof is on you for having made the statement in the first place.
>
> > They damage your brain damage and interfere with your mood, this is not opinion but fact.In vivo, in vitro, which species, which dosages? There is no such thing as FACT in science. There are only disconfirmed null-hypotheses.
-Ll
Posted by rjlockhart '05 on August 10, 2008, at 11:05:06
In reply to Re: Freud, Cocaine, and Adderall, posted by West on August 10, 2008, at 9:15:49
Posted by dbc on August 10, 2008, at 11:10:46
In reply to Re: Freud, Cocaine, and Adderall, posted by West on August 10, 2008, at 10:46:48
I see benzo.org.uk board is still in full swing pushing their same agenda. All of us thats been around know not to engage you in these conversations.
Yes lets argue about the most researched psychiatric drug in history. Your fight is ideological not scientific. I wonder why a refined and intellectual dr like Mrs. Ashton allows your people to use her name for this agenda of misinformation and cherry picked studies. Do you ever wonder what sort of damage you do to ill people looking for help?
Posted by rjlockhart '05 on August 10, 2008, at 11:11:40
In reply to Re: Freud, Cocaine, and Adderall » West, posted by SLS on August 10, 2008, at 10:55:38
From what i've read. Cocaine is not nuertoxic? And Amphetamine is?....well i knew that. Methamphetamine destroys dopmaine whatever you call them, nuerons.
Funny Dextroamphetamine has been on the US market benzedrine(amph) and dexedrine(d-amp) pattented 1932?
By the way....Adderall used to be called "Obertrol" in the 60's. They removed it, and replaced when adderall was introduced in '96.Wow.
Posted by SLS on August 10, 2008, at 11:28:09
In reply to Re: So concluding......, posted by rjlockhart '05 on August 10, 2008, at 11:11:40
> From what i've read. Cocaine is not nuertoxic? And Amphetamine is?....well i knew that. Methamphetamine destroys dopmaine whatever you call them, nuerons.
From some of the most current literature, amphetamine induced neurotoxity is spoken about as if already proven. I really don't know what the truth is. I know that up until a few years ago, methamphetamine was considered the major culprit, and not dexamphetamine. There was plenty of debate back then. I imagine there still is.
The UK has a real problem with the abuse of amphetamine provided by illicit sources. It seems far worse there than in the USA. Perhaps this motivates the search for neurotoxicity. I would just like to see more evidence and more discussion before scaring the hell out of people.
- Scott
Posted by dbc on August 10, 2008, at 11:29:18
In reply to Re: So concluding......, posted by rjlockhart '05 on August 10, 2008, at 11:11:40
> From what i've read. Cocaine is not nuertoxic? And Amphetamine is?....well i knew that. Methamphetamine destroys dopmaine whatever you call them, nuerons.
>Thats a favorite little excerpt from a study that the DEA/agencies affiliated with the war on drugs like to use. What they fail to mention is that the meth users in the study only used IV methamphetamine. Yes the speed of the onset of injected methamphetamine potentially burns out dopamine receptors.
This does not mean oral methamphetamine does. Infact the only difference between methamphetamine and amphetamine is the methyl moleculte that causes more amphetamine to pass through the blood brain barrier.Also bare in mind that illicit methamphetamine users use massive doses at once timw (quarter grams/half grams or more). Comparing this to the average 5mg - 10mg therapeutic oral dose of d-amphetamine (dexedrine) is ridiculous.
Posted by dbc on August 10, 2008, at 11:53:00
In reply to Re: So concluding......, posted by SLS on August 10, 2008, at 11:28:09
> The UK has a real problem with the abuse of amphetamine provided by illicit sources. It seems far worse there than in the USA. Perhaps this motivates the search for neurotoxicity. I would just like to see more evidence and more discussion before scaring the hell out of people.
>From first hand accounts of users in the UK the amphetamine is very subpar and meth is pretty much non-existant as is any substantial quanity of dexedrine. Neurotoxic effects of the amphetamine available may be the result of impurities created during production.
I've heard recently though that research chemicals such as MDPV (Methylenedioxypyrovalerone) and Methylone (2-methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one)
have gained popularity as grey market stimulants and they may result in damage being attributed to amphetamine as absolutely nothing is known about they substances beyond initial research.The UK also always has a plentiful supply of cheap and pure MDMA given its proximity to holland.
Posted by Deputy Dinah on August 10, 2008, at 12:06:25
In reply to Re: Freud, Cocaine, and Adderall, posted by West on August 10, 2008, at 9:15:49
> Do you realise how crazy you all sound?
Please don't post anything that could lead others to feel accused or put down.
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Posted by Deputy Dinah on August 10, 2008, at 12:12:03
In reply to Re: Freud, Cocaine, and Adderall, posted by dbc on August 10, 2008, at 11:10:46
> I wonder why a refined and intellectual dr like Mrs. Ashton allows your people to use her name for this agenda of misinformation and cherry picked studies. Do you ever wonder what sort of damage you do to ill people looking for help?
Please respect the views of others even if you think they're wrong. Please don't post anything that could lead others to feel accused or put down.
If you or others have questions about this or about posting policies in general, or are interested in alternative ways of expressing yourself, please see the FAQ:
http://www.dr-bob.org/babble/faq.html#civil
Follow-ups regarding these issues should be redirected to Psycho-Babble Administration. They, as well as replies to the above posts, should of course themselves be civil.
Dr. Bob is always free to override deputy decisions. His email is on the bottom of each page. Please feel free to email him if you believe this decision was made in error.
Dinah, acting as deputy to Dr. Bob
Posted by Deputy Dinah on August 10, 2008, at 12:18:23
In reply to Please be civil » dbc, posted by Deputy Dinah on August 10, 2008, at 12:12:03
Thanks for responding in a civil manner.
Dr. Bob really appreciates it when posters present a balancing point of view in a civil and respectful manner. Thanks, Nadezda and Scott for the following:
Well, I'm sure it is not just you alone.
It never seemed bizarre to me. I think one must be careful to not generalize to the majority what one as an individual experiences with treatment. It is possible to be angry at a drug for mistreating you, thus your wanting to take it away from people who need it.
Taking Adderall is a necessity for people for whom it works to improve their condition, whether it be ADD/ADHD or depression. Some people respond well to Adderall whom failed to respond to Dexedrine or Ritalin. Clinically, Adderall is useful and not nearly as addicting as cocaine.- Scott
You need to distinguish between medications that didn't help one or some people and medications that don't help anyone-- or, alternatively, medications that you had problems with and medications that everyone has problems with.
I wouldn't make a useful med unavailable to everyone because some people have problems with it.
I've used adderall for several years and it's been of great help to me. I'm sure, from reading this board, that I"m not the only person who has.Nadezda
Dinah, acting as deputy to Dr. Bob
Posted by West on August 10, 2008, at 16:22:05
In reply to Re: Freud, Cocaine, and Adderall, posted by West on August 10, 2008, at 9:15:49
Scott you rightly say the onus is on me to prove it. I am under the impression, as might have become clear, that the deleterious effects are common scientific knowledge, in the same way one would no longer dispute global climate change. Clearly this is not the case.
West
http://www.ncbi.nlm.nih.gov/pubmed/16014752?dopt=AbstractPlushttp://jpet.aspetjournals.org/cgi/reprint/jpet.105.087916v1.pdf
Also amphetamine neurotoxicity is not a peculiarly Britain concept relegated to an underclass of so called street-drug users. Speculating that impurities or the addition of other much rarer stimulants like 4-mar seem rather baseless when the primary constituents found in sold speed int his country are glucose and caffeine. I may be wring but what sense would there be in cutting a low cost £5-10 a gramme drug with hard to manufacture and rarer, more expensive, chemicals?
Posted by West on August 10, 2008, at 16:32:40
In reply to Amphetamine neurotoxicity in therapeutic doses, posted by West on August 10, 2008, at 16:22:05
My crap english is i hope uncharacteristic, i have heavy hands today. apologies (read 'British' instead of 'Britain')
Posted by SLS on August 10, 2008, at 16:37:19
In reply to Amphetamine neurotoxicity in therapeutic doses, posted by West on August 10, 2008, at 16:22:05
Thanks for the citations. I wish you had not been able to come up with any.
:-(
I'll have to give this a lot more thought.
- Scott
Posted by West on August 10, 2008, at 16:40:32
In reply to Amphetamine neurotoxicity in therapeutic doses, posted by West on August 10, 2008, at 16:22:05
The second link, yes, is a study in adult non-human primates. To be honest i didn't even read it, you'll find it on the second page of google.
I don't think i am fear mongering but providing information where it may be of some help, however marginal.
Posted by dbc on August 10, 2008, at 16:46:38
In reply to Re: Amphetamine neurotoxicity in therapeutic doses, posted by West on August 10, 2008, at 16:40:32
But what is the point? I wonder what Anon would think of benzo.org, im sure they'd be interested in the forum.
Posted by desolationrower on August 10, 2008, at 16:50:58
In reply to Re: Amphetamine neurotoxicity in therapeutic doses, posted by West on August 10, 2008, at 16:40:32
There is evidence of change in dopamine neurones after use of amphetamines, little of it is clearly applicable to human and therapeutic doses. Calling this 'neurotoxic' is not warranted from the evidence currently availible though. For instance, DATs are overexpressed for people with ADHD and reducing there number would be a benefit from chronic treatment. This would be consistent with the therapeutic benefit often extending past the time one takes the drug.
Posted by West on August 10, 2008, at 17:08:38
In reply to Re: Amphetamine neurotoxicity in therapeutic doses, posted by desolationrower on August 10, 2008, at 16:50:58
Potentially yes, and the theory is a neat one. Since I do not have ADD I cannot comment on how effective something like adderall is in treating that condition. I can say i still think that from a safety perspective, all other existing agents should be tried before taking it.
Posted by cumulative on August 10, 2008, at 23:58:27
In reply to Amphetamine neurotoxicity in therapeutic doses, posted by West on August 10, 2008, at 16:22:05
It is my opinion that the changes in dopamine transporters in that study reflect plastic changes, not neurotoxicity. Homeostatic changes in the dopamine transporter (and many other systems -- some of which seem to sensitize) are well-known to occur with dopaminergic psychostimulants, and that study does not show anything different. Also, ever since his hysterical MDMA mess-ups (where it was later found that they accidently used methamphetamine instead of MDMA, later being long after MDMA's neurotoxicity was trumpeted all over the news media) I don't really trust anything coming out of Ricaurte's lab. Other than that study, neurotoxicity from dextroamphetamine (unlike dextromethamphetamine, which has an additional mechanism of neurotoxicity that has a good chance of being active at therapeutic dosing, due to its serotonergic affinity) neurotoxicity is not known to occur at anything near human therapeutic doses of amphetamine.
Posted by West on August 11, 2008, at 16:00:05
In reply to Re: Amphetamine neurotoxicity in therapeutic doses, posted by dbc on August 10, 2008, at 16:46:38
>>But what is the point? I wonder what Anon would think of benzo.org, im sure they'd be interested in the forum.
I originally decided to ignore this post since the one you posted prior to it seemed rather confused and off-topic, i thought you'd lost your way a bit since we were discussing amphetamines not benzos. If you're trying to portray me as some kind of extremist out to chastise unwell people then i can promise you that i am not that person having suffered depression and anxiety for 6 years myself.
My concern is that tons of americans and their children are taking this drug in good faith without knowing about its neuropharmacology and i'm sure that, if they knew more about its action, they would open themselves up to making more educated decisions when it comes to treating their ADD/ADHD. The layman for instance might, when asked which treatment he preferred, settle on adderall, perhaps saying 'it was the only one that worked' for him when plausibly he might just have preferred the feeling it engendered in him, unaware of amphetamine's euphoric effects. Who wouldn't prefer a drug which directly arouses feelings of interest and pleasure- it's a neurochemical non sequitur.
So a second issue exists with their safety which is marginalised by the drug's strong reinforcing effects, to me nothing spells trouble like a potent releaser of monoamines. MDMA + MDA are both examples of phenylethlamines known to induce the redistribution and release of chemicals in the brain; both are well documented neurotoxins.
I just read a study which i will look for again which attributed d-amphetamine's primary neurotoxic effects at room temperature to hypothermia, similar effects were seen with ephedrine I believe.
Posted by linkadge on August 12, 2008, at 15:56:22
In reply to Re: Amphetamine neurotoxicity in therapeutic doses, posted by desolationrower on August 10, 2008, at 16:50:58
I don't think this study should be shrugged off. I think this study is applicable to human usage, and I would personally be very concerned about the potential for theraputic use of amphetamines and other related compounds to cause neurotoxicity.
You can bet though that its not Shire that is going to be rushing out any time soon to fund follow up studies.
Also, DAT transporters are *not* upregulated in ADHD. This is a stupid hypothesis (which is not supported by the majority of studies) based on the mechanism of action of the stimulants. Its just about as believable as the notion that serotonin transporters are elevated in depression.
Linkadge
Posted by linkadge on August 12, 2008, at 16:01:25
In reply to Re: Amphetamine neurotoxicity in therapeutic doses, posted by linkadge on August 12, 2008, at 15:56:22
In defense though, I do not believe that euphoria is the mechanism of action of the amphetamines in ADHD. There are plenty of euphoriants which do not improve ADHD symptoms.
A fixed dose of amphetamine will only provide mood improvement for a short length of time (days or weeks at best), but they can be effective in ADHD for years.
I am still concerned though about the potential for neurotoxicity. There are other issues too which concern me, namely the long term cardiac side effects of stimulants and atomoxetine. Also a metabolite of methylphenidate has strong binding to 5-ht2b receptors and could pose risk to cardiac valves in a similar manner to the withdrawn dopamine agonists permax and cabergoline.
Linakdge
Posted by Dade on August 13, 2008, at 18:48:20
In reply to Re: Amphetamine neurotoxicity in therapeutic doses, posted by linkadge on August 12, 2008, at 15:56:22
"Also, DAT transporters are *not* upregulated in ADHD".Perhaps not *all* ADHD patients but *some*?
"This is a stupid hypothesis (which is not supported by the majority of studies) based on the mechanism of action of the stimulants. Its just about as believable as the notion that serotonin transporters are elevated in depression."
LinkadgeAgreed, similar to the theory that Schizophrenia is caused by overactive dopamine systems.
Thou studies have often shown high doses of amphetamines cause notorious shaking and loss of balance, low doses (10-15mgs) D-amp improve steadiness and balance, alertness, attention, hand eye coordination, especially in fatigued persons. long distance truckers call amphetamines "co-pilots".
Posted by Dade on August 13, 2008, at 18:56:29
In reply to re: Ricaurte therapeutic dose study., posted by cumulative on August 10, 2008, at 23:58:27
> It is my opinion that the changes in dopamine transporters in that study reflect plastic changes, not neurotoxicity. Homeostatic changes in the dopamine transporter (and many other systems -- some of which seem to sensitize) are well-known to occur with dopaminergic psychostimulants, and that study does not show anything different. Also, ever since his hysterical MDMA mess-ups (where it was later found that they accidently used methamphetamine instead of MDMA, later being long after MDMA's neurotoxicity was trumpeted all over the news media) I don't really trust anything coming out of Ricaurte's lab. Other than that study, neurotoxicity from dextroamphetamine (unlike dextromethamphetamine, which has an additional mechanism of neurotoxicity that has a good chance of being active at therapeutic dosing, due to its serotonergic affinity) neurotoxicity is not known to occur at anything near human therapeutic doses of amphetamine.
hi there....desoxyn = (S)-methamphetamine, and dexedrine = d-amphetamine. There is a body of literature that reports that methamphetamine is about twice as potent as d-amphetamine. potency is derived from dose/response evaluations of subjects, and i can point you to several citations that conclude that (S)-methamphetamine and d-amphetamine are actually equipotent. HOWEVER, it turns out that (in at least 1 study examining a D_{1} antagonist) the mechanisms of neurotoxicity at high doses of desoxyn and dexedrine are different, as the antagonist protected against death from dexedrine in a dose-dependent fashion but not for desoxyn. (Derlet et al., Life Sci. 47:821-827 (2000)). but, the equipotency has been established, too. [e.g., Woolverton et al., Pharmacol. Biochem. Behav. 13:869-876 (1980)]. but then, see Peachey et al., Psychopharmacology 51:137-140 (1977) for evidence of greater stimulation (not potency) of desoxyn than dexedrine. more recently, Melega et al. JPET 274:90-96 (1995) concluded that low doses of either drug exhibited similar pharmacokinetics and dopamine response, although this is not a measure of potency nor were the doses extreme. from an abstract by Ellison and Switzer in Neuroreport. 25:17-20 (1993), they report (i quote) ``Both [dexedrine] and [cocaine] induced pronounced degeneeration in fasciculus retroflexus, but only [dexedrine] further induced substantial degeneration in striatum...[Desoxyn] administered in the very high dose but less prolonged drug regimen often employed in studies of dopamine toxicity induce pronounced degeneration in striatum, but widespread degeneration in many other regions as well.'' and then there is one paper by the man who instigated the FDA to make MDMA illegal: Ricaurte et al., Neuropharmacology 22:1165-1169 (1983), in which ``Repeated administration of large doses of [desoxyn] produce long-lasting depletion of brain dopamine and serotonin, as well as persistent decreases in the activity of their respective biosynthetic enzymes...'' interestingly, dexedrine - in ``a comparable regimen'' to the desoxyn dosing - ``did not did not produce long-lasting depletion of 5-HT in either the neostriatum or hippocampus.'' but, it turns out (and not just in this ref) that pretreatment with fluoxetine likely inhibits metabolism of amphetamines in general. so, in summary: potency is derived from dose/response curves, and in low doses, it appears as if desoxyn and dexedrine exhibit similar pharmacokinetics and are somewhat equipotent. however, at high doses of both drugs, the potency of desoxyn is greater and the toxicity is, as well, due to the larger amount of the brain affected in re: dopamine and 5-HT response. most drugs exhibit linear pharacokinetics/dynamics in the recommended dose ranges. the LD_{50} for desoxyn and dexedrine are almost identical, but at higher doses, desoxyn is more lethal. finally, as i posted some time ago, the study by (again) Ricaurte et al. in Science 297:2260-2263 (2003) entitled ``Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA (``ecstact'')'' - which was later retracted because the drugs given to the 5 monkeys tunred out to be methamphetamine and not MDMA - is actually testament to the neurotoxicity to methamphetamine (desoxyn). the dose was 6 mg/kg over 6 hours. recalling that this was pure methamphetamine, this means that your 100 mg desoxyn would correspond to your weight at about 16 kg, or about 35 lbs. 1 monkey died, 1 was unable to continue after the second dose (dosing was 2 mg/kg tid), and the 3 surviving monkeys were examined over several weeks after the acute dosing (there's more, and i can send you the PDF of the article if you desire, or anyone else). conclusions: severe dopaminergic injury and serotonergic neuortoxicity (for subjects using methamphetamine in repeated doses over several hours). the implication is that using desoxyn for a prolonged period - which is essentially what this last study showed - is bad news compared to dexedrine. hope this helps, and all the best,
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