Sciencemadness Discussion Board

Models to authoratively quantitate human addiction potential of compounts and mixtures.

SM2 - 26-7-2012 at 08:08

seemingly "Good Studies" rating addictiveness, which are hogwash.


Right now, I think the whole study (especially NIDC) is bullock. Nicotine being the most addictive drug? Why, because so many people are habituated to using it? That might make it the most used, amongst drugs of variable addiction potential, if it weren't for the fact that until recently, there was way more than neat nicotine going into your lungs if you are a smoker. For me, quitting cigarettes was fairly easy. No need to quit alcohol simply because I like my wine and beer too much to not stop. Too much alcohol (which is a shitty drug any way) just get's to the tipping point of negative added value. Just don't want more than a beer or so. And I truly feel bad for those Irish Catholic American Indians. I'd say, generally, chemicals involved in changes of the shape of the brain, especially mesolimbic, are going to be the real ones difficult to cold turkey off of. Also, these types of drugs which have more than one effect. Something like tramadol which is an opioid of the morphine type, and also has acute SSRI/SNRI effects. Of course, the Ketibemidone and dipipnone for die hards, and mode of administration (NEVER bang anything!

But there are many fancy and some good ways to get off opioids. Don't start. Cold turkey (the unpleasant memory may inoculate you against further use).

But by far the best way if already hooked, is a slow gradual taper, while exercising and drinking plenty of water, and eating plenty of healthy food. You need to give your brain time to revert, and it's not always quick.

Eventually, many drugs which cause intense euphoria, are like MDMA in that (it doesn't do anything for me anymore). Sorry if this post is off topic. And I ramble too much. Apparently, I must just like the sound of my own voice :(

zoombafu - 26-7-2012 at 09:44

Look up ibogaine therapy, its pretty interesting actually and has been pretty successful for at helping people with addiction problems.

chemrox - 26-7-2012 at 10:38

there is no such word as "quantitate." I found nicotine the hardest substance to rid myself of. I think opioids with high lipid affinity would rank pretty high too. On a basic level you have to define what you mean by 'addiction.' I tend to follow de Stevens in asserting that it means tolerance and physical dependance. If you wanted to quantify those parameters the first would be fairly easy to measure. The second can be approached on many levels. For example the number of opioid receptors can be measured. In animal studies you can simply observe drug seeking behavior. I would suggest lipophilicity might be an independent variable of great significance in drug dependance studies. What is confusing in all these approaches is the role of dopamine receptors. In opioid studies this aspect seems to be totally ignored in favor of the opioid receptor family. Fentanyl is called a 'pure mu agonist.' It also may be a dopamine agonist. Heroin and other opiates as well as some opioids seem to be antidepressants. Amphetamines don't cause any kind of physical abstinence syndrome yet we have this worldwide problem. In fact there are cultures that have used methcathinone in herb form for centuries. The most profitable drug trades in the last century have been in drugs that are "non-addictive" in the classical sense. Cocaine and methamphetamine. I hear the Russian mafia has come with a cathinone or amphetamine so dirty it's guaranteed to kill you within a year and people are buying the shit, getting amputations and dying loaded on it. I think more studies focusing on the dopamine and serotonin systems will will change what we call addiction. It may turn out that extinction of the dopamine receptors is the most deadly kind of addiction there is.

[Edited on 26-7-2012 by chemrox]

SM2 - 26-7-2012 at 15:00



Yeah, I think I remember hearing Heroin, oxymorphone, and buprenorphine having some anti-depressant qualities. Amphetamine causes drain bamage, but not cocaine, it only changes shapes. That shit you were hearing about in Russia, nic named Crocidiale, is a chlorocodide derivative made from readily available codeine. Nothing is purified, and the physical damage looks worse than the after math of a Brown Recluse bite. Yes, what you said regarding serotonin. It is so much more involved in opioid/NAC shell train than was once thought. Really enjoyed reading your stuff chemrox;)

[Edited on 26-7-2012 by Fennel Ass Ih Tone]

chemrox - 1-8-2012 at 22:45

Thanks Fennel- and for the correction especially- now I remember. The Russians were souping up crude codeine with chloroform and junkyard catalysts to make the dirtiest oxymorphone imaginable. It's called "crocodile" for the way it makes the skin look before it falls off. This is all from hyped news stories though...

AllisterCaine - 9-8-2012 at 14:33

another great method for quitting opioids is loperamide. it activates only the peripheral opioid receptors, BUT by feedback endorphine is released inside the brain.

i cant imagine ever getting addicted to nicotine, really. its more of a "social problem". its everywhere, and so much people do smoke. i tend to smoke on a party when im bored or something....

Organikum - 9-8-2012 at 21:38

Quote: Originally posted by chemrox  
there is no such word as "quantitate." I found nicotine the hardest substance to rid myself of. I think opioids with high lipid affinity would rank pretty high too. On a basic level you have to define what you mean by 'addiction.' I tend to follow de Stevens in asserting that it means tolerance and physical dependance. If you wanted to quantify those parameters the first would be fairly easy to measure. The second can be approached on many levels. For example the number of opioid receptors can be measured. In animal studies you can simply observe drug seeking behavior. I would suggest lipophilicity might be an independent variable of great significance in drug dependance studies. What is confusing in all these approaches is the role of dopamine receptors. In opioid studies this aspect seems to be totally ignored in favor of the opioid receptor family. Fentanyl is called a 'pure mu agonist.' It also may be a dopamine agonist. Heroin and other opiates as well as some opioids seem to be antidepressants. Amphetamines don't cause any kind of physical abstinence syndrome yet we have this worldwide problem. In fact there are cultures that have used methcathinone in herb form for centuries. The most profitable drug trades in the last century have been in drugs that are "non-addictive" in the classical sense. Cocaine and methamphetamine. I hear the Russian mafia has come with a cathinone or amphetamine so dirty it's guaranteed to kill you within a year and people are buying the shit, getting amputations and dying loaded on it. I think more studies focusing on the dopamine and serotonin systems will will change what we call addiction. It may turn out that extinction of the dopamine receptors is the most deadly kind of addiction there is.

[Edited on 26-7-2012 by chemrox]


Thats not the russian but the international pharma-mafia and the compound in question is "tianeptine" which when injected causes gangrene because of the fillers in the pills. There are plenty of very gross videos about this online.

"Extinction" of dopamine receptors caused by methamphetamine in special is avoided completely by supplementing selene as antioxidant, many studies on this are available. It speaks of the mindless cruelity of anti-drugs warriers and authorities that this fact is not published widely to reduce harm, supplying selene supplements to hardcore users (similar to syringes for junkies) would be the logical way to go. But, no, they want people to suffer.

In short every really working antidepressive is addictive by definition. It is astonishing how much effort is employed to enforce the calvinist/lutheran antihedonism instead of giving those suffering the wellknown compounds which really help and which are much less evil then benzodiazepines are. What is an addiction compared to live in a grey world under a sky which resembles a concrete roof just 10cm above your head?

/ORG

SM2 - 11-9-2012 at 06:15

Well let's put it this way. I would GLADLY have a reputable Dr./surgeon implant electrodes into certain deep areas of my brain, so I would give myself a little (or big) shot of pure pleasurable reward. I'm not embaressed, and nothing is really sacred any more, I'd probably grow long hair just so I had a place to put it, and of course, would be nice if it was water proof, ran off 1 AAA battery, and had multiple settings, from intense orgasm, to different forms of dopaminageric stimulations. I'd pay for that. Are there any doctors who do this/.
Quote: Originally posted by chemrox  
there is no such word as "quantitate." I found nicotine the hardest substance to rid myself of. I think opioids with high lipid affinity would rank pretty high too. On a basic level you have to define what you mean by 'addiction.' I tend to follow de Stevens in asserting that it means tolerance and physical dependance. If you wanted to quantify those parameters the first would be fairly easy to measure. The second can be approached on many levels. For example the number of opioid receptors can be measured. In animal studies you can simply observe drug seeking behavior. I would suggest lipophilicity might be an independent variable of great significance in drug dependance studies. What is confusing in all these approaches is the role of dopamine receptors. In opioid studies this aspect seems to be totally ignored in favor of the opioid receptor family. Fentanyl is called a 'pure mu agonist.' It also may be a dopamine agonist. Heroin and other opiates as well as some opioids seem to be antidepressants. Amphetamines don't cause any kind of physical abstinence syndrome yet we have this worldwide problem. In fact there are cultures that have used methcathinone in herb form for centuries. The most profitable drug trades in the last century have been in drugs that are "non-addictive" in the classical sense. Cocaine and methamphetamine. I hear the Russian mafia has come with a cathinone or amphetamine so dirty it's guaranteed to kill you within a year and people are buying the shit, getting amputations and dying loaded on it. I think more studies focusing on the dopamine and serotonin systems will will change what we call addiction. It may turn out that extinction of the dopamine receptors is the most deadly kind of addiction there is.

[Edited on 26-7-2012 by chemrox]

AJKOER - 13-9-2012 at 15:12

Quote: Originally posted by chemrox  
there is no such word as "quantitate." I found nicotine the hardest substance to rid myself of. I think opioids with high lipid affinity would rank pretty high too. On a basic level you have to define what you mean by 'addiction.' I tend to follow de Stevens in asserting that it means tolerance and physical dependance. If you wanted to quantify those parameters the first would be fairly easy to measure. The second can be approached on many levels. For example the number of opioid receptors can be measured. In animal studies you can simply observe drug seeking behavior. I would suggest lipophilicity might be an independent variable of great significance in drug dependance studies. What is confusing in all these approaches is the role of dopamine receptors. In opioid studies this aspect seems to be totally ignored in favor of the opioid receptor family. Fentanyl is called a 'pure mu agonist.' It also may be a dopamine agonist. Heroin and other opiates as well as some opioids seem to be antidepressants. Amphetamines don't cause any kind of physical abstinence syndrome yet we have this worldwide problem. In fact there are cultures that have used methcathinone in herb form for centuries. The most profitable drug trades in the last century have been in drugs that are "non-addictive" in the classical sense. Cocaine and methamphetamine. I hear the Russian mafia has come with a cathinone or amphetamine so dirty it's guaranteed to kill you within a year and people are buying the shit, getting amputations and dying loaded on it. I think more studies focusing on the dopamine and serotonin systems will will change what we call addiction. It may turn out that extinction of the dopamine receptors is the most deadly kind of addiction there is.


I think Chemrox has suggested several good possible indicators for the dependent variable. However, there can only be one Y variable, so I would suggest the following process.

First, construct a panel of 'experts' on addiction. Next, have them rate a sample of addicts on a scale of 1 to 10 (a judgmental construct of the Y). Then, regress the observed judgmental Ys against your observed suggested independent variables (like number of opioid receptors, lipophilicity,..) by subject. The X variables can be assumed to be at first linearly related, then add quadratic terms, or apply a log or square-root transformation to obtain the best fit. If one variable clearly explains nearly all the error, then choose it as your Y. If a weighted average of several variables does really much better, use it as the objective Y variable.

Another method, use robust ('model free') regression techniques.

If nothing works, this is an important result. It may mean that the reputed panel of experts are no better than chance (full of BS) or your Xs have no predictive powers of the level of addiction (just noise), so choose an arbitrary X or weighted average thereof to be your Y, or a judgmental construct from a group of experts.


[Edited on 13-9-2012 by AJKOER]

Yo-Yo - 22-9-2012 at 23:25

Medical chemistry aside (like following the lipinsky rule of five fives) a drugs addictive potential is tested by a standardized range of animal experiments, such as looking if the substance is self-administered by the animal. However, when translating these data into human abuse potential the social acceptance of the substance use is extreamly important. That's why drugs like nicotine crops up as having higher abuse potential than say opiates.