|
Install Gentoo posted:The people being stigmatized are already actually using it legally though? There's nothing illegal about taking prescribed medicine yet that's what they're being treated as criminals over. It sounds to me like you don't have a lot of experience filling C-II scripts. In college I suffered through a lot of bullshit just filling Adderall scripts, which is C-II but in no way as stigmatized as oxycontin. quote:My point is that we're not going to get people using certain drugs out of being treated like criminals and bad people just because the drugs in question become more legalized.
|
#
?
Jan 24, 2013 17:19
|
|
|
|
| # ? Jun 1, 2024 01:32 |
|
|
Chitin posted:As for methamphetamine and PCP, the argument is the same as heroin; they are very bad drugs, but prohibition does nothing but make things worse for the user and society. All of the evidence we have is that use of these drugs does not go up under legalization; that people are more likely to find treatment; and that the issues that come with an underground drug market (crime rings, dirty drugs, exploding trailer parks) are eliminated. The "bigger badder drugs" part of it holds no water. The entire reason meth is A Thing is because of crackdowns on dexamphetamine (commonly known as Adderall). If you give people legal Adderall then demand for meth is going to shrivel up pretty hard. This would also have the side benefit of unfucking the situation with ADD meds - currently it's very difficult to get them filled legally, because the DEA licenses batches of them and they permit less to be manufactured than doctors actually write. This is leaving aside the fact that meth isn't the devil it's made out to be. Legal meth is prescribed to literal children under the brand name Desoxyn, it's another situation like heroin where most of the harm comes from lovely bathtub manufacture and being cut with who the gently caress knows what.
|
|
#
?
Jan 24, 2013 17:21
|
|
|
Paul MaudDib posted:This is leaving aside the fact that meth isn't the devil it's made out to be. Legal meth is prescribed to literal children under the brand name Desoxyn, it's another situation like heroin where most of the harm comes from lovely bathtub manufacture and being cut with who the gently caress knows what. I think this applies to recreational abuse of any substance. You can't really downplay meth's demonization by society, though. It's one of the most addictive substances out there and really fucks up people's lives.
|
|
#
?
Jan 24, 2013 17:28
|
|
|
somnolence posted:I think this applies to recreational abuse of any substance. You can't really downplay meth's demonization by society, though. It's one of the most addictive substances out there and really fucks up people's lives. There's more to it though. Pharmaceutical oral methamphetamine isn't great, but it's also not all that much worse than pharmaceutical oral amphetamine or dextroamphetamine. The reason that meth has become this great terror is that is that the lack of availability of clean drugs leads people to (a) adulterated substances and (b) methods of administration that maximize absorption (smoking, shooting, insufflation). If methamphetamine was magicked out of existence, the exact problems you see with meth abuse today would apply to whatever amphetamine was synthesized for illicit use in its place.
|
|
#
?
Jan 24, 2013 17:37
|
|
|
somnolence posted:I think this applies to recreational abuse of any substance. You can't really downplay meth's demonization by society, though. It's one of the most addictive substances out there and really fucks up people's lives. It's important to note that methamphetamine is not dependence-forming; it's addictive like gambling, not addictive like cigarettes, alcohol or heroin. This isn't to downplay the horrible consequences of meth addiction, but saying it's "one of the most addictive substances out there" is overplaying it quite a bit. As noted above, a huge proportion of meth use is for performance enhancing purposes, and meth generally becomes the stimulant of choice in places where cocaine is less available. The "Faces of Meth" campaign is hardly a good resource on what average methamphetamine use entails.
|
|
#
?
Jan 24, 2013 17:42
|
|
|
Dusseldorf posted:Who would get weed from a dealer if there were any legal options available whatsoever. Ultimately prices and availability will affect that. Right now we have no idea of either. I expect the black market to continue at least on a smaller scale. People growing their own and selling/trading with their friends is not legal without a permit. There might not even be permits available or reasonably priced to allow that.
|
|
#
?
Jan 24, 2013 18:17
|
|
|
spengler posted:It sounds to me like you don't have a lot of experience filling C-II scripts. In college I suffered through a lot of bullshit just filling Adderall scripts, which is C-II but in no way as stigmatized as oxycontin. Eh no dude, I've been on C-II meds for the past 15 years. And ADHD meds aren't nearly as stigmatized as oxy yet they're both equally legal - thus proving my point that mere legality isn't enough. I would bet that if you asked people their general opinion of people who take painkillers all the time versus people who use marijuana all the time, you'd find that marijuana use is generally found to be way less of a "bad thing" even though marijuana is more illegal in more places than painkillers are.
|
|
#
?
Jan 24, 2013 18:40
|
|
|
Install Gentoo posted:Eh no dude, I've been on C-II meds for the past 15 years. And ADHD meds aren't nearly as stigmatized as oxy yet they're both equally legal - thus proving my point that mere legality isn't enough. I think you have a skewed idea of demographics - being on opiate pain maintenance is pretty common in communities where there's a lot of manual labor. Anyway, the primary reason opiates are hard to get at ERs is drug-seeking behavior - opiate addicts looking for a fix. If they can get their fix elsewhere, legally, there is no reason for them to be in the ER in the first place, so there's no suspicion involved.
|
|
#
?
Jan 24, 2013 18:52
|
|
|
spengler posted:It sounds to me like you don't have a lot of experience filling C-II scripts. In college I suffered through a lot of bullshit just filling Adderall scripts, which is C-II but in no way as stigmatized as oxycontin. I'm curious as to what types of bullshit. What can there be beside you hand them the paper and wait for your name to be called. They ask you for ID?
|
|
#
?
Jan 24, 2013 19:06
|
|
|
EBT posted:Or your doctor just not treating your pain all the way to not get hassled. This outcome seems especially likely if you're poor, non-white, and/or a woman.
|
|
#
?
Jan 24, 2013 20:29
|
|
|
I know that in the case of desoxyn, every year or so I have to deal with an inability to fill my script due to some artificial shortage of the generic. It eventually comes back in stock, but the price always goes up along with it. $350 for a month's supply? That's some bullshit for sure. I've never attempted to abuse amphetamines but I bet its cheaper than that on the street. That's at a pretty tiny dose, too.
|
|
#
?
Jan 24, 2013 20:31
|
|
|
Red_Mage posted:What about PCP? Methamphetamine? Substituted cathinone? "Substituted cathinone" is not a drug, it's a class of derivatives from cathinone, some of which are quite laid back. For example methylone which is basically MDMA light. Of course there's also MDPV and other similar substances but you clearly don't know what you're talking about if you're trying to imply that they are all in the same league as meth or pcp. Ideally in a fully legalized and regulated market we would have pharmaceutical companies researching new, better, safer recreational drugs and users and addicts would switch over. Those overly terrible drugs would eventually just be left in the dust. Like for example, probably the biggest reason Mephedrone got so absurdly big for a while was that there was basically a global MDMA shortage. No doubt it wouldn't have taken off in nearly the same way if the pills weren't all piperazines back then. Provide people with good, reasonably safe drugs and most everyone will stick to that instead of using more dangerous alternatives.
|
|
#
?
Jan 24, 2013 20:48
|
|
|
Cakebaker posted:"Substituted cathinone" is not a drug, it's a class of derivatives from cathinone, some of which are quite laid back. For example methylone which is basically MDMA light. Of course there's also MDPV and other similar substances but you clearly don't know what you're talking about if you're trying to imply that they are all in the same league as meth or pcp. The difference in level of knowledge and vocabulary between those arguing for prohibition and against is just staggering. It's like everyone in this thread clamoring to BAN THE EVIL DRUGS hasn't done even a basic level of reading on the subject.
|
|
#
?
Jan 24, 2013 21:26
|
|
|
LeftistMuslimObama posted:The difference in level of knowledge and vocabulary between those arguing for prohibition and against is just staggering. It's like everyone in this thread clamoring to BAN THE EVIL DRUGS hasn't done even a basic level of reading on the subject. They probably haven't because the only logical conclusion one can draw from actually looking at the facts of prohibition is that it is an utter failure in every single way. Well except for the part where private prison operators get unbelievably wealthy for doing hideous things to poor people. That part works pretty well.
|
|
#
?
Jan 25, 2013 02:47
|
|
|
Chitin posted:It's important to note that methamphetamine is not dependence-forming; it's addictive like gambling, not addictive like cigarettes, alcohol or heroin. This isn't to downplay the horrible consequences of meth addiction, but saying it's "one of the most addictive substances out there" is overplaying it quite a bit. As noted above, a huge proportion of meth use is for performance enhancing purposes, and meth generally becomes the stimulant of choice in places where cocaine is less available. The "Faces of Meth" campaign is hardly a good resource on what average methamphetamine use entails. Maybe I have a biased view on the subject because the city I grew up in and the surrounding areas were infested with meth heads and much of the crime in my city was related to both that drug and the epidemic of people smoking oxycontin. Can you cite a source that says that methamphetamine does not form physical dependence as opiates and alcohol do? Also, I'd love to see a citation for your claim that a "huge proportion" of meth is used for performance enhancement. somnolence fucked around with this message at 05:56 on Jan 25, 2013 |
|
#
?
Jan 25, 2013 05:54
|
|
|
Install Gentoo posted:They are already taking legal regulated opiates, dude. Yes, but being stigmatized and having to jump through hoops with the doctors, pharmacists, and insurance companies just to get the medicine they need. Look up the phrase "I'm not comfortable filling this for you."
|
|
#
?
Jan 25, 2013 06:18
|
|
|
LeftistMuslimObama posted:The difference in level of knowledge and vocabulary between those arguing for prohibition and against is just staggering. It's like everyone in this thread clamoring to BAN THE EVIL DRUGS hasn't done even a basic level of reading on the subject. I hope that the drug policies in this country eventually reflect a realization that prohibition simply doesn't work. However, I don't think that such policies will ever fully stop the abuse of drugs found on the black market.
|
|
#
?
Jan 25, 2013 06:25
|
|
|
somnolence posted:Maybe I have a biased view on the subject because the city I grew up in and the surrounding areas were infested with meth heads and much of the crime in my city was related to both that drug and the epidemic of people smoking oxycontin. Can you cite a source that says that methamphetamine does not form physical dependence as opiates and alcohol do? Also, I'd love to see a citation for your claim that a "huge proportion" of meth is used for performance enhancement. First of all let's define the difference between dependence and addiction. The terms are very muddy in the discourse and are often used interchangeably, but there are medical meanings to be found. Dependence as a medical term means that, absent the substance, your body will suffer acute physical withdrawal symptoms. For example, the experience of withdrawing from alcohol (Delirium Tremens or "the DTs") can be fatal. You can be dependent on your heart medication, caffeine, certain antidepressants, heroin, benzodiazepines, and probably a few other things I'm probably forgetting. Addiction is a very ill-defined term with no medical meaning. You can be addicted to gambling, shopping, marijuana, the internet (coming soon the the DSM V! Maybe!), hallucinogens, food, the stimulant drugs, you name it. Generally speaking, addiction absent dependence describes compulsive behavior and cycles that can be difficult or impossible to break. To say that methamphetamine is addictive but not dependence forming is in no way a slight to those suffering from methamphetamine addiction. Withdrawal symptoms from an addiction are psychological and psychosematic; speaking personally, when I don't get my amphetamines in the form of Adderall, I feel lackadaisical, withdrawn, distracted in tired, but I'm not writhing in bed in agony. Wikipedia on Methamphetamine withdrawal posted:Withdrawal symptoms of methamphetamine primarily consist of fatigue, depression, and increased appetite. Symptoms may last for days with occasional use and weeks or months with chronic use, with severity dependent on the length of time and the amount of methamphetamine used. Withdrawal symptoms may also include anxiety, irritability, headaches, agitation, restlessness, excessive sleeping, vivid or lucid dreams, deep REM sleep, and suicidal ideation. Wikipedia on Marijuana withdrawal posted:Common symptoms of cannabis withdrawal include low mood, irritability, anxiety, difficulty sleeping, and muscle pain.[2] Symptoms typically begin within a day after stopping cannabis intake, and last up to two weeks. Another way of making the distinction is to use the terms "psychical" and "physiological" addiction, as is done in the Wikipedia article on the subject: http://en.wikipedia.org/wiki/Substance_dependence As for my claim that a lot of methamphetamine use is performance-enhancing: British Columbia Ministry of Health Services posted:A diverse population uses methamphetamine and for various reasons. Methamphetamine use can result in increased energy, performance enhancement, loss of appetite, weight loss and heightened sexual drive. Methamphetamine use seems prevalent among street youth, youth involved in the rave dance scene, and gay men. http://www.google.com/url?sa=t&rct=...9,d.dmQ&cad=rja This seems obvious on its face. Methamphetamine is a powerful, long-lasting stimulant, which is useful for anyone who needs to be awake or forgo sleep for long periods of time. Truck drivers are a good example. There's also a long history of methamphetamine use in sports. Anecdotally, methamphetamine is popular with grad students and doctors. Chitin fucked around with this message at 17:37 on Jan 25, 2013 |
|
#
?
Jan 25, 2013 17:26
|
|
|
Previa_fun posted:Yes, but being stigmatized and having to jump through hoops with the doctors, pharmacists, and insurance companies just to get the medicine they need. Look up the phrase "I'm not comfortable filling this for you." And making it "more legal" won't make that stigmatization go away. They're going to continue treating people taking it poorly for quite a long time afterwards. They are putting things in the way because they believe that a lot of people only want it to get high (which most likely isn't true) and having it more legal isn't going to make that go away.
|
|
#
?
Jan 25, 2013 17:49
|
|
|
Install Gentoo posted:And making it "more legal" won't make that stigmatization go away. They're going to continue treating people taking it poorly for quite a long time afterwards. They are putting things in the way because they believe that a lot of people only want it to get high (which most likely isn't true) and having it more legal isn't going to make that go away. You don't think laws and the governments official stance on a given issue influences this kind of perception? The fact that certain drugs are illegal builds in a certain level of stigmatization. Take away the legal stigma and some of the social stigma will change too. I doubt it would ever get to the point of people accepting recreational IV drug use but I'd be willing to bet there would be fewer doctors looking at people cross-eyed and trying to second guess their motivation when they ask for pain medication.
|
|
#
?
Jan 25, 2013 18:17
|
|
|
Install Gentoo posted:And making it "more legal" won't make that stigmatization go away. They're going to continue treating people taking it poorly for quite a long time afterwards. They are putting things in the way because they believe that a lot of people only want it to get high (which most likely isn't true) and having it more legal isn't going to make that go away. Again, this is because doctors and pharmacists have been found liable in the past when people have abused the drugs they prescribe. Doctors have gone to jail for prescribing too many pain meds, even when their primary business is opiate pain management. It's not just a stigma thing, it's that they fear if they give out opiate pain medication too freely they could lose their license. In a world where doctors could legally prescribe opiates for addiction maintenance, or in a world where you wouldn't have to go to your doctor to get opiates, this wouldn't be an issue. Would there be doctors not comfortable with prescribing and pharmacists not willing to fill? Sure, that's true with Plan B as well. Would the problem be nearly so widespread? Clearly not.
|
|
#
?
Jan 25, 2013 19:00
|
|
|
It's almost moot what with the recent FDA recommendation that hydrocodone be more tightly controlled. Well just have to enjoy our Tylenol and NSAIDs. ...and legal marijuana. 
|
|
#
?
Jan 26, 2013 00:36
|
|
|
Chitin posted:First of all let's define the difference between dependence and addiction. The terms are very muddy in the discourse and are often used interchangeably, but there are medical meanings to be found. Methamphetamine is absolutely dependency forming and it is heartbreaking to see some psychiatrists still using it and other amphetamine-class drugs as first line treatment for ADD/ADHD. The amphetamine-class drugs work by opening up the synaptic vesicles containing dopamine into the synaptic cleft and flooding it with dopamine; this is a complete abuse of the dopaminergic pathways and is toxic to the brain so the brain adjusts by producing less and less dopamine over time. There's also the effect on the neuron that the movement of the synaptic vesicles caused by amphetamines is too fast for the cell to keep up, so it disrupts the cell membrane at the 5HT receptor sites and will literally destroy these axons. The idea that you can flood your synaptic cleft with a neurotransmitter, completely overriding the cell's protection mechanisms and stay fine and dandy is a fairy tale. Until recently, we didn't know exactly what the long term effects of a relatively low dose of amphetamines over a period of say 10 years would do to the dopaminergic pathways, but new evidence shows that it is still neurotoxic. People who have been administered amphetamines over a long period will remain dependent on them (and progressively higher doses at that) for normal dopamine functioning for their entire lives. I remember experimenting on lab rats chronically administered amphetamines and seeing them progressively lose all memory function; the same appears to be happening in humans as we see older chronic amphetamine users develop Parkinson's at an alarming rate. Fortunately, a lot of psychiatrists are seeing the new studies and responding appropriately by refusing to prescribe amphetamines to anything but the most recalcitrant cases of ADD/ADHD. Their aren't a lot of alternatives to amphetamines yet but we have atomoxetine (Strattera) and bupropion (Wellbutrin) (in off-label use) which are much safer norepinephrine reuptake inhibitors. There's also methylpehnidate (Ritalin) but it has such a strong dopamine reuptake inhibitor component that it really shouldn't be prescribed unless atomoxetine or bupropion are ineffective.
|
|
#
?
Jan 27, 2013 01:12
|
|
|
elgatofilo posted:People who have been administered amphetamines over a long period will remain dependent on them (and progressively higher doses at that) for normal dopamine functioning for their entire lives. That's odd, because I've been prescribed them for most of my life, and I've pretty consistently reduced my dose as I got older. I also took four years off from age 17 to 21, as well as regularly taking a few days off here and there, and the only thing I experience is a return of my ADHD symptoms. I guess you are sort of right in a round-about way, because my dopamine function is naturally pretty hosed up (and always has been, due to my ADHD). So I guess the fact that amphetamines make my dopamine system function normally is a good thing in my case. I would agree that adderall et al are way overprescribed, but for people who actually have ADHD or whatever you want to call a malfunctioning reward system in their heads it's the only thing that lets me live a normal life. At any rate, strattera and wellbutrin didn't do anything for me, aside from wellbutrin making me feel like I was always about to have a seizure. To get back to the topic at hand, however, I'd like to point out that my old ADHD doctor (who developed this: http://en.wikipedia.org/wiki/Test_of_Variables_of_Attention) once told me that small amounts of THC were probably the best method of treating my ADHD, provided that I could actually find a place to get standardized doses. wilfredmerriweathr fucked around with this message at 02:19 on Jan 27, 2013 |
|
#
?
Jan 27, 2013 01:59
|
|
|
elgatofilo posted:Methamphetamine is absolutely dependency forming and it is heartbreaking to see some psychiatrists still using it and other amphetamine-class drugs as first line treatment for ADD/ADHD. You paint a bleak picture of medicinal amphetamine use which is not consistent with what I have read: quote:
Methamphetamine in child psychiatry: http://online.liebertpub.com/doi/abs/10.1089/cap.1993.3.iv KingEup fucked around with this message at 04:29 on Jan 27, 2013 |
|
#
?
Jan 27, 2013 04:26
|
|
|
wilfredmerriweathr posted:That's odd, because I've been prescribed them for most of my life... KingEup posted:You paint a bleak picture of medicinal amphetamine use which is not consistent with what I have read: The neurotoxicity of methamphetamine has been empirically proven and can be observed by anyone with a properly equipped lab in vitro. If you administer methamphetamine to a lab rat in a large enough dose or over a long enough amount of time, its 5HT axons in key dopaminergic pathways will be destroyed leaving only the cell bodies, I have literally seen this with my own eyes. How doctor's deal with this information depends largely on the patient and is more an ethical issue than a biomedical one. I'm not suggesting that someone go around with an untreated illness, there are many medications that have potentially toxic side-effects but the side-effects are better than the illness itself. ADD/ADHD can be a debilitating illness and recalcitrant cases which don't respond to safer drugs or behavioral therapy can be treated with amphetamines as long as the patient understands that this carries a far greater risk. My problem is with the position that amphetamines are some sort of miracle drug and fun for the whole family, rather than a dangerous drug of last resort: This a fairy tale, there are no panaceas. To address the articles you linked: The article on prescribing amphetamines to children is 20 years old and predates the modern findings on methamphetamine, the development of atomoxetine and, most importantly, the APA rules on disclosure of researcher's ties to pharmaceutical companies in published journal articles. The other article you linked is sort of an odd meta analysis of some of the methamphetamine literature to date. The article admits that the great majority of literature on the subject is negative in nature and then sort of bounces between trivial observations (well this study found amphetamines impair memory function but they didn't find that it did so on the 3rd Monday of April under the light of a full moon!) and some good suggestions for future research directions that I wouldn't be surprised to find have been conducted since this article was published. This kind of meta analysis is good for determining what kind of research to do but very bad at debunking empirical biological research (in the sense that it doesn't at all). The reason I say it's an odd article is because it struck me as glibly dismissive of extremely strong biological research in favor of far less reliable and limited statistical analysis of outcomes in drug using populations. Drug using populations are infamously difficult to study reliably. In any case, here's some of the many articles that pop up using "methamphetamine" and "cognitive" as key words in PubMed: Chronic methamphetamine exposure produces a delayed, long-lasting memory deficit. http://www.ncbi.nlm.nih.gov/pubmed/23280858 quote:Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment. Methamphetamine use: A comprehensive review of molecular, preclinical and clinical findings. http://www.ncbi.nlm.nih.gov/pubmed/23273775 quote:Extended use of MA is associated with many health problems that are not limited to the central nervous system, and contribute to increased morbidity and mortality in drug users. Numerous studies, using complementary techniques, have provided evidence that chronic MA use is associated with substantial neurotoxicity and cognitive impairment. Methamphetamine influences on brain and behavior: unsafe at any speed? http://www.ncbi.nlm.nih.gov/pubmed/22709631 quote:Methamphetamine damages monoamine-containing nerve terminals in the brains of both animals and human drug abusers, and the cellular mechanisms underlying this injury have been extensively studied. More recently, the growing evidence for methamphetamine influences on memory and executive function of human users has prompted studies of cognitive impairments in methamphetamine-exposed animals...
|
|
#
?
Jan 27, 2013 10:13
|
|
|
Some of the literature I've read states that the physical effects of methamphetamine on the brain's dopamine receptors lead to what others in this thread have referred to as psychological addiction. Wouldn't this place methamphetamine in the same class of drugs as others that cause physical dependency? I don't see where the line is drawn between the two (that is, psychological addiction and physical dependency) as far as methamphetamine is concerned. It seems to me that the psychological effects that others have pointed out are a result of the body's physical dependency on the drug to activate dopamine receptors in the brain. While the detox/withdrawl period may not be as severe as opiates or alcohol, isn't this the same sort of effect? Maybe I'm beating a dead horse, but I have yet to see conclusive evidence that methamphetamine is not dependence forming on a physical level. Is the problem that the research hasn't been done or am I missing something? Enlighten me, please.
|
|
#
?
Jan 27, 2013 11:15
|
|
|
elgatofilo posted:words Do you have any thoughts about provigil/modafinil being used for focus/attention problems in adults?
|
|
#
?
Jan 27, 2013 11:41
|
|
|
elgatofilo posted:The amphetamine-class drugs work by opening up the synaptic vesicles containing dopamine into the synaptic cleft and flooding it with dopamine; this is a complete abuse of the dopaminergic pathways and is toxic to the brain so the brain adjusts by producing less and less dopamine over time. There's also the effect on the neuron that the movement of the synaptic vesicles caused by amphetamines is too fast for the cell to keep up, so it disrupts the cell membrane at the 5HT receptor sites and will literally destroy these axons. elgatofilo posted:The neurotoxicity of methamphetamine has been empirically proven and can be observed by anyone with a properly equipped lab in vitro. If you administer methamphetamine to a lab rat in a large enough dose or over a long enough amount of time, its 5HT axons in key dopaminergic pathways will be destroyed leaving only the cell bodies, I have literally seen this with my own eyes. 1) You suggest that chronic methamphetamine use results in downregulation of actual dopamine production rather than receptors, correct? I'd like to read more about that if so. 2) I'm confused why you keep mentioning serotonin receptors being disrupted in key dopaminergic pathways by a dopaminergic drug. Why / how are 5HT receptors involved? 3) The qualifier 'a large enough dose / over a long enough period of time' suggests to me that axon destruction is a pretty extreme end result that isn't likely to occur in most normal use cases - am I correct?. This sound similar to the (false) claims that MDMA use will make 'holes in your brain' - while I'm sure the results you describe could occur with a large enough dose I'm dubious that it's something any normal user would experience. Not to say that meth is fine and dandy and we should all go get some because I do still think it's a Bad Idea.
|
|
#
?
Jan 27, 2013 12:24
|
|
|
elgatofilo posted:The neurotoxicity of methamphetamine has been empirically proven and can be observed by anyone with a properly equipped lab in vitro. If you administer methamphetamine to a lab rat in a large enough dose or over a long enough amount of time, its 5HT axons in key dopaminergic pathways will be destroyed leaving only the cell bodies, I have literally seen this with my own eyes. How doctor's deal with this information depends largely on the patient and is more an ethical issue than a biomedical one. I'm not suggesting that someone go around with an untreated illness, there are many medications that have potentially toxic side-effects but the side-effects are better than the illness itself. ADD/ADHD can be a debilitating illness and recalcitrant cases which don't respond to safer drugs or behavioral therapy can be treated with amphetamines as long as the patient understands that this carries a far greater risk. My problem is with the position that amphetamines are some sort of miracle drug and fun for the whole family, rather than a dangerous drug of last resort: This a fairy tale, there are no panaceas. Also, the other posters were specifically talking about dependency on prescribed meth. I've also taken Adderall in the long term (almost 10 years), and have never noticed any withdrawal effects, aside from the immediate return of my normal ADD symptoms. And I generally don't have trouble stopping for days and weeks at a time, so long as I don't have any important work to do.
|
|
#
?
Jan 27, 2013 15:25
|
|
|
somnolence posted:While the detox/withdrawl period may not be as severe as opiates or alcohol, isn't this the same sort of effect? Uh, no, not at all. Why would you expect the effects of withdrawal from a stimulant to be the same as those of depressants? Alcohol, like a benzo or a barbiturate, binds to neurons' GABAa receptors, positively modulating (beefing up) the action of the inhibitory neurotransmitter. Over long enough periods of use, your body down-regulates production of GABA, leading to tolerance (needing a larger dose for the same effect). When you suddenly stop modulating what little GABA your body is still producing after a long period of use of one of these drugs, you're left with not enough GABA to get the required neuroinhibitory work done and you suddenly have a lot more neural activity than you ought to. This is why alcohol and benzo withdrawal can kill you if it's bad enough. What is another way of describing a massive excess of neural activity? A seizure, that's right. I don't know much about opiates and their associated withdrawal, but I know they cause major serotonin dysfunction in long-term users, which means withdrawing from them would basically make it neurochemically impossible to enjoy life until you start producing adequate amounts of serotonin again. Opiate withdrawal can't kill you, however. The whole crux of physical dependency is that your body down-regulates production of neurotransmitters over time if you're regularly creating conditions of excess. Your body is smarter than you are. It's just insanity to say that amphetamines do not create physical dependency. It is a dopamine releasing agent. You cannot flood your synaptic clefts with massive amounts of any of the monoamines on any sort of regular basis and not expect a dependency to form. Your body isn't stupid. It knows what's going on. It's not going to stand idly by while you literally poison your brain with too much dopamine for any significant period of time. It's going to cut back on production to compensate. But it can't ramp production back up any quicker than it can cut it back (hence the time it takes for dependence to a drug to emerge), which is why you get withdrawals. And what are the symptoms of amphetamine withdrawal? Depression, dysphoria, and with increasing and alarming frequency due to overprescription, psychosis. Exactly what you expect a person to be afflicted with when there's not enough dopamine in their brain. Just about every drug has a place somewhere in medicine. Amphetamines are not a boogey-man to be feared and hated. But they are also not happy fun times for free. Their place is not as front-line maintenance medication for easily distracted college students who want to be able to study better. Smudgie Buggler fucked around with this message at 16:03 on Jan 27, 2013 |
|
#
?
Jan 27, 2013 16:01
|
|
|
Smudgie Buggler posted:Uh, no, not at all. Why would you expect the effects of withdrawal from a stimulant to be the same as those of depressants? I should have been more clear, I meant the effect of your body going through physical withdrawl, not that the effects of the withdrawl were the same. somnolence fucked around with this message at 16:14 on Jan 27, 2013 |
|
#
?
Jan 27, 2013 16:11
|
|
|
TACD posted:I've read more about MDMA than actual methamphetamine so I'm willing to accept the broad points you make, but I have three questions: 1) Yes, the brain downregulates dopamine to protect itself (dopamine itself is neurotoxic in large quantities), but if the DA axons are destroyed, then the receptors are destroyed along with it. In vivo neuroimaging studies show strong evidence that amphetamine users have less DA receptors than control groups. The meta analysis I posted previously has a good overview of the exact mode of action of methamphetamine that's actually not too complicated and has pictures and everything: Methamphetamine use: A comprehensive review of molecular, preclinical and clinical findings. http://www.ncbi.nlm.nih.gov/pubmed/23273775 The wikipedia article on methamphetamine/amphetamine is not too great really, probably because it's been edited by the usual subjects, which is a shame because it's feigning controversy and doubt over amphetamines when there's a lot of great research out there and near universal consensus amongst neuroscientists on this subject. It's like pulling up the article on bacteria and finding whole sections casting doubt on whether the theory of bacteria really disproves abiogenesis (because how can you really be sure life doesn't arise spontaneously?) 2) You are correct in observing that even though amphetamines mostly act on the DA axons, the 5HT axons seem especially vulnerable to damage from them. The mechanism for this is not completely understood, but it seems that the cell membrane is simply more vulnerable to damage because of the type of transporter present at these terminals. Additionally, it's possible rats have a neuroprotective component in their DA axons but not their 5HT axons. It's been theorized that humans don't have this neuroprotective capacity so there's equal or more damage at the DA axons and 5HT axons in humans. If you have training in cell biology and want to know more about the exact mechanism, this is a good study conducted by Molliver et al. on the process: Dual Serotonin (5-HT) Projections to the Nucleus Accumbens Core and Shell: Relation of the 5-HT Transporter to Amphetamine-Induced Neurotoxicity http://www.jneurosci.org/content/20/5/1952.short The basic mechanism for cell damage remains the same though: Dopamine is kept inside the cell in bubbles called vesicles, what amphetamine does is it makes the cell transport a large number of these vesicles to the cell membrane at once. Cells are not designed to have a bunch of holes in their cell membrane at once so the axons rupture, leaving only the cell body. 3) It's not clear what a safe dose is over a long period of time, the FDA approved methamphetamine for ADD/ADHD based only on short term studies and there's good evidence that the therapeutic window (the range for which a dose is effective but not neurotoxic) for amphetamines is vanishingly small. Then there's the problem with downregulation of dopamine requiring higher doses to maintain the same effectivity, a responsible psychiatrist will never titrate a dose much above the original dose; but, there's no accounting for what a patient might do with a drug (Oh, I need an extra boost today, so I'm going to take 4 pills!) and once axons are gone they're gone for good. I've noticed a lot of people commenting in this thread that they've used amphetamines for years at the same dose and haven't felt any ill effects. I don't really want to comment on this because everyone is different and case studies are cool but they're not really evidence one way or the other, these kinds of discussions can't be made generic: They are personal decisions patients make with their doctors. I will note that downregulation of dopamine is also an empirically proven effect of amphetamine use (at any dose), so it logically follows that a greater dose is necessary to maintain the same effect. What this means for any particular person's treatment plan is variable and might be worth discussing with your psychiatrist or prescriber if you have any concerns. What a lot of psychiatrists will do is take the patient off of it for a few months while dopamine production (hopefully) ramps back up. moller posted:provigil/modafinil This is a newer class of drugs and some psychiatrists have an "anything-but-amphetamines" attitude towards pharmacological treatment of ADD/ADHD right now, so they might be tempted to use modafinil and armodafinil off-label. But in general, the more cellular mechanisms a drug disrupts the less safe it probably is, this is the reason psychiatrists prefer NRIs and SSRIs over amphetamines and MAOIs, respectively. There isn't nearly as much research on modafinil as there is on amphetamines though and there's the problem of pharmaceuticals really wanting to push armodafinil as the new miracle drug that makes you smarter.
|
|
#
?
Jan 27, 2013 21:31
|
|
|
elgatofilo posted:I've noticed a lot of people commenting in this thread that they've used amphetamines for years at the same dose and haven't felt any ill effects. I don't really want to comment on this because everyone is different and case studies are cool but they're not really evidence one way or the other, these kinds of discussions can't be made generic: They are personal decisions patients make with their doctors. I will note that downregulation of dopamine is also an empirically proven effect of amphetamine use (at any dose), so it logically follows that a greater dose is necessary to maintain the same effect. What this means for any particular person's treatment plan is variable and might be worth discussing with your psychiatrist or prescriber if you have any concerns. What a lot of psychiatrists will do is take the patient off of it for a few months while dopamine production (hopefully) ramps back up. The part of your previous post that I replied to was this part; of course, my sample size is 1, which isn't very empirically significant! But I literally have not experienced any tolerance, and it has in fact gone the other way. Over the years I have become *more* sensitized to amphetamines, and have repeatedly requested dose decreases from my doctor. My experience has been backed up by those of others that I have spoken to with ADHD, as well as being something that my doctor has seen in a number (but by no means all) of his other patients. The oft-repeated "amphetamines build tolerance" line just seems to be completely backwards in my experience. Maybe I'm just special. The main point that I'm trying to get across is that I think we can all agree that long term use of recreational doses of amphetamines will undoubtedly have negative impacts on a person's health, especially that of their brain's reward pathways. But I have always found a paradoxical effect at the therapeutic levels that I have been prescribed; instead of losing the ability to enjoy life, I gain it - both while on my medication and during break periods. Instead of becoming tolerant, I become able to get the same therapeutic effects from smaller and smaller doses (I'm talking once daily sub-10mg doses here.) That could be the big difference, as the average recreational user goes for 100+mg and would easily do over a gram in a day if they were on a bender. It does bug me that people assume that I will lose all my teeth, become a junkie, etc because of this stuff. They hear "meth" and have a kneejerk reaction, telling me of all the horrors the drug will do to my body and mind. It just doesn't work that way. I'm sure the stigma is part of the reason that whatever pharmaceutical company is making it this year can charge so goddamned much for it. wilfredmerriweathr fucked around with this message at 23:46 on Jan 27, 2013 |
|
#
?
Jan 27, 2013 23:00
|
|
|
wilfredmerriweathr posted:The part of your previous post that I replied to was this part; of course, my sample size is 1, which isn't very empirically significant! But I literally have not experienced any tolerance, and it has in fact gone the other way. Over the years I have become *more* sensitized to amphetamines, and have repeatedly requested dose decreases from my doctor. My experience has been backed up by those of others that I have spoken to with ADHD, as well as being something that my doctor has seen in a number (but by no means all) of his other patients. The oft-repeated "amphetamines build tolerance" line just seems to be completely backwards in my experience. Maybe I'm just special. The reason I noted earlier that drug using populations are notoriously hard to study is because people in general are hard to study, especially on a taboo subject. Amphetamines are a highly stigmatized medication and the effects users feel are shaped by their cultural and social environments as well. It doesn't seem likely to me that someone with ADD/ADHD taking amphetamines would openly admit to developing tolerance for the drug, people usually don't admit to developing tolerance to any drug, much less to one as stigmatized as methamphetamine as it suggests they are now "addicts" which is certainly not a desirable outcome. The reason "amphetamines build tolerance" is oft repeated is because it's the outcome of decades of brain research trickling into the general concousness. Amphetamines are partially responsible for the discovery of neurotransmitter downregulation and it's used for this purpose in hundreds of studies that have nothing to do with amphetamines. Whenever you need a rat/rabbit/guinea pig to have less dopamine production in its brain for whatever experiment you're conducting, you give it amphetamines. I don't want to appear callous towards this issue, but the empirical and positivist biomedical model of medicine forces us to regard evidence in this order: 1. Direct experimental observations. 2. Controlled clinical trials. 3. Longitudinal studies. 4. Case series and clinical experience. 5. Case studies. Because 1 and 2 trump 3, 4 and 5, when evidence from 3,4 and 5 contradicts evidence from 1 and 2 we are forced to refactor our observations to align with 1 and 2, this is the principle of parsimony (Occam's razor). It's certainly possible that there exists persons which actually become more sensitive to the effects of amphetamine over time through an as of yet unknown mechanism, but this has not been observed. Ultimately, this is a bioethical issue that is actually not unique to psychiatry: If you have a medication that is dangerous but can help a person live a better life, do you administer the medication? I personally feel that patients should be able to choose dangerous medical treatments as long as they are fully informed of the risks and benefits, and amphetamines carry many risks for comparatively few benefits when compared to other available medications. For a psychiatrist to dispense amphetamines like they're skittles without due process of informing the patient of evidence of harm and betting the patient simply will never experience harm strikes me as paternalistic and disingenuous.
|
|
#
?
Jan 28, 2013 00:02
|
|
|
elgatofilo posted:The basic mechanism for cell damage remains the same though: Dopamine is kept inside the cell in bubbles called vesicles, what amphetamine does is it makes the cell transport a large number of these vesicles to the cell membrane at once. Cells are not designed to have a bunch of holes in their cell membrane at once so the axons rupture, leaving only the cell body. I'm curious about the effect you mention in the part I quoted though. I'm a user of MDMA, not meth, but I know it has a similar action (reversing the behaviour of serotonin reuptake transporters and dumping it all into the cleft) but I've never heard of this kind of damage in the literature I've read. Is this something DA neurons are more susceptible to? How does this destroy the whole axon and not just the terminal? If this is covered in the studies you posted just let me know and I'll find out when I get to them.
|
|
#
?
Jan 28, 2013 00:28
|
|
|
elgatofilo posted:
I'm really having to call you out on this. In medicine in no way do in vivo animal models and especially in vitro studies offer a higher standard of evidence than randomized control trials, particularly the subsequent meta-analysis and systematic reviews of these. Neither of these approaches reflect the full complexity of clinical, social, psychological and biological factors in practice. As such, they don't really factor directly into clinical decision making, but rather to inform targets for clinical research. They are instead useful to narrow things down and suggest relationships, but I wouldn't necessarily extrapolate the harm caused by amphetamines across different species with any sweeping conclusions just yet. The bigger picture needs to be considered first, and that will come from further clinical studies. Iamthegibbons fucked around with this message at 02:11 on Jan 28, 2013 |
|
#
?
Jan 28, 2013 01:44
|
|
|
Iamthegibbons posted:I'm really having to call you out on this. In medicine in no way do in vivo animal models and especially in vitro studies offer a higher standard of evidence than randomized control trials, particularly the subsequent meta-analysis and systematic reviews of these. Neither of these approaches reflect the full complexity of clinical, social, psychological and biological factors in practice. As such, they don't really factor directly into clinical decision making, but rather to inform targets for clinical research. I'm not sure how to engage this post, it's not clear what your complaint is or what you're "calling me out" on, are you seriously suggesting that neurotransmitter downregulation doesn't exist or what? Direct experimental observation is the cornerstone of all sciences, everything in the biomedical model has to be grounded in what can be directly observed. I'm certain that you know experimenting on humans is unethical, you can't administer varying doses of amphetamines to human subjects and then take slices out of their brains, dye them with silver nitrate and look at it under a microscope to see the axonal degeneration; however, you can do this with rats. In the interest of conducting ethical science, certain animal models can serve in lieu of humans even though the correlation between rats and humans is not perfect. Randomized controlled trials are fantastic; however, statistical analysis has its limits: data can be noisy, data collection can be unreliable, effect strength can be too small for the sample size, participant mortality, observer effect, placebo effect, and on and on. I'm aware that biological experimentation is limited in the scope of what it can tell us and that no one form of data is conclusive evidence, but science is hierarchical in nature and we must defer to the data roughly in the order I listed. What kind of research do you believe would form sufficient evidence? The way you're putting it it seems like no amount of ethically gathered evidence could ever satisfy. If anything, I'm being very conservative in my assessment of the data, reading most of the meta-analysis on amphetamine research I see the authors are far more dire and many go as far as to suggest that it should be pulled from the market entirely. I'm not making any "sweeping conclusions" as you put it, but a conservative assessment of an extremely well studied compound (I'd be hard-pressed to find a more well studied compound, let alone a psychotropic). You're right that clinical decision making is different from other scientific considerations, if anything, it should be far more conservative and guarded; normally, medications have been pulled from the market if there exists even a hint that it could cause harm (Rimonabant comes to mind) the FDA and the medical establishment can't afford to have trust in it eroded by careless prescribing. Methamphetamine prescriptions didn't begin in earnest until the 90's, what if we discover in the future that the link between methamphetamine and Parkinson's is concrete? what would you say to the sufferers? "Oops! We just didn't want to make any sweeping conclusions, sorry!" Some might feel comfortable with this outcome; I consider this to be human experimentation and is an ethically unacceptable position for me to take.
|
|
#
?
Jan 28, 2013 04:21
|
|
|
I'm pretty sure they're not calling you out on anything. They're just disagreeing with the heirarchy of evidence because they think it's somehow hugely important that evidence from the first category has very seldom come from human experimental subjects (at least in neuroscience) since the late 40s.
|
|
#
?
Jan 28, 2013 10:11
|
|
|
|
| # ? Jun 1, 2024 01:32 |
|
|
elgatofilo posted:Some might feel comfortable with this outcome; I consider this to be human experimentation and is an ethically unacceptable position for me to take. Pharmaceutical companies make enough off of these drugs to pay the damages from the class action suits and still walk away with billions lining their coffers. No harm no foul, right? 
|
|
#
?
Jan 28, 2013 13:05
|
|