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Thread: Gene linked to cannabis use disorder also linked to nicotine addiction

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    Gene linked to cannabis use disorder also linked to nicotine addiction



    See:
    https://www.nature.com/articles/s41593-019-0416-1

    "Cannabis is the most frequently used illicit psychoactive substance worldwide; around one in ten users become dependent. The risk for cannabis use disorder (CUD) has a strong genetic component, with twin heritability estimates ranging from 51 to 70%. Here we performed a genome-wide association study of CUD in 2,387 cases and 48,985 controls, followed by replication in 5,501 cases and 301,041 controls. We report a genome-wide significant risk locus for CUD (P = 9.31 × 10−12) that replicates in an independent population (Preplication = 3.27 × 10−3, Pmeta-analysis = 9.09 × 10−12). The index variant (rs56372821) is a strong expression quantitative trait locus for cholinergic receptor nicotinic α2 subunit (CHRNA2); analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with CUD in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance. The results provide biological insights and inform on the genetic architecture of CUD."




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    I don't believe in that. What's up with this math??

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    Quote Originally Posted by LecrameMark View Post
    I don't believe in that. What's up with this math??
    Please feel free to read the entire paper and explain to us where the mathematical errors appear.

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    My uncle is a stoner and was also a cigarette smoker until he transitioned to e-cigs; my sister never used marijuana but smoked cigarettes for a little over a decade before quitting cold turkey when she got pregnant with my nephew back in 2010, and my brother uses marijuana recreationally but never touched tobacco. So here is a few examples that run the gamut of tobacco vs. marijuana use.

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    The findings of this research seem quite plausible to me. A genetic influence on drug use is only a tendency, so it's possible to find counter-examples. If there is a gene associated with drug addiction, it seems unlikely that it would be confined to only one specific drug. The concept of an "addictive personality" is not new. That is, people who easily become addicted to one thing have a tendency to become addicted to other things.

    What interests me is that only one in ten cannabis users become dependent on the drug. How does that compare with tobacco users? I suspect that the great majority of smokers are dependent on (addicted to) nicotine. Even the ten per cent of cannabis users who are dependent do not necessarily have a "disorder" unless their dependence causes harm to themselves or others (which it does in some cases, but maybe not in every case).

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    1 members found this post helpful.
    Quote Originally Posted by Tamakore View Post
    The findings of this research seem quite plausible to me. A genetic influence on drug use is only a tendency, so it's possible to find counter-examples. If there is a gene associated with drug addiction, it seems unlikely that it would be confined to only one specific drug. The concept of an "addictive personality" is not new. That is, people who easily become addicted to one thing have a tendency to become addicted to other things.

    What interests me is that only one in ten cannabis users become dependent on the drug. How does that compare with tobacco users? I suspect that the great majority of smokers are dependent on (addicted to) nicotine. Even the ten per cent of cannabis users who are dependent do not necessarily have a "disorder" unless their dependence causes harm to themselves or others (which it does in some cases, but maybe not in every case).
    I think there is something to that. Hard core drug users who wind up going through the criminal justice system are usually addicted to multiple drugs, and almost always nicotine is among them.

    However, what is also clear among that population is that there are clear drug "preferences". While almost all of them are addicted to nicotine (which I think may be among the drugs with the highest addictive propensity), some definitely want heroin; some want stimulants, some don't drink alcohol at all, but do do other hard drugs, some mix the drugs with alcohol.

    From lengthy conversations with experts, and reading the papers, drug addiction of any kind, including alcohol addiction, is co-morbid with a lot of psychiatric disorders like anxiety, clinical depression, bi-polar disorder and schizophrenia.

    Addicts may be choosing the drugs which have the most "positive" effect on their precise psychiatric disorder.

    The worrisome thing is that if a person has a genetic propensity to these psychiatric disorders, and begins using them in early adolescence, it may trigger the disorder, or at least make it worse. We know, for example, that people with a family history of bi-polar disorder and schizophrenia and even people who may carry the "candidate" genes, will be more likely to develop the disorder in late adolescence if there has been some traumatic event in their lives. Injecting recreational drugs into their still forming brains is a very bad idea. The young brain is more fragile and open to change than people think.

    There are also differences by "ethnicity". In the "Interesting maps and graphs" thread I posted statistics from the EU about psychiatric disorders by country. The types vary, and so does the rate of alcohol and drug addiction. Italy's rate is rather low by comparison, although it certainly exists. It's been known for years that it has a low alcoholism rate by comparison even to France, and much lower than that of Northern and Eastern populations. Yet, from personal observation, I would bet that their addiction to nicotine is as high or higher than that of many other countries.

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    Quote Originally Posted by Angela View Post
    I think there is something to that. Hard core drug users who wind up going through the criminal justice system are usually addicted to multiple drugs, and almost always nicotine is among them.

    However, what is also clear among that population is that there are clear drug "preferences". While almost all of them are addicted to nicotine (which I think may be among the drugs with the highest addictive propensity), some definitely want heroin; some want stimulants, some don't drink alcohol at all, but do do other hard drugs, some mix the drugs with alcohol.

    From lengthy conversations with experts, and reading the papers, drug addiction of any kind, including alcohol addiction, is co-morbid with a lot of psychiatric disorders like anxiety, clinical depression, bi-polar disorder and schizophrenia.

    Addicts may be choosing the drugs which have the most "positive" effect on their precise psychiatric disorder.

    The worrisome thing is that if a person has a genetic propensity to these psychiatric disorders, and begins using them in early adolescence, it may trigger the disorder, or at least make it worse. We know, for example, that people with a family history of bi-polar disorder and schizophrenia and even people who may carry the "candidate" genes, will be more likely to develop the disorder in late adolescence if there has been some traumatic event in their lives. Injecting recreational drugs into their still forming brains is a very bad idea. The young brain is more fragile and open to change than people think.

    There are also differences by "ethnicity". In the "Interesting maps and graphs" thread I posted statistics from the EU about psychiatric disorders by country. The types vary, and so does the rate of alcohol and drug addiction. Italy's rate is rather low by comparison, although it certainly exists. It's been known for years that it has a low alcoholism rate by comparison even to France, and much lower than that of Northern and Eastern populations. Yet, from personal observation, I would bet that their addiction to nicotine is as high or higher than that of many other countries.
    I agree that recreational drug use is a high risk activity for adolescents and should be discouraged as much as possible. I'm glad in retrospect that I was 23 when I tried cannabis for the first time. It was just good luck that no one had offered it to me earlier, since I had no knowledge back then of the link between drug use and psychiatric disorders in developing brains. The trick may be to get adolescents to agree among themselves that drug use is "uncool". This seems to have happened with tobacco, at least in some countries.

    It would be interesting to find out to what extent the different rates of drug and alcohol addiction in different countries reflect differences in the distribution of risk alleles across countries. Cultural differences and government policies will also be factors. To take an extreme example, I'm sure the rate of alcoholism in Saudi Arabia is very low, because the strong cultural and governmental prohibitions on alcohol mean that most people with a genetic predisposition to alcoholism will probably never drink it even once.

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    Quote Originally Posted by Tamakore View Post
    I agree that recreational drug use is a high risk activity for adolescents and should be discouraged as much as possible. I'm glad in retrospect that I was 23 when I tried cannabis for the first time. It was just good luck that no one had offered it to me earlier, since I had no knowledge back then of the link between drug use and psychiatric disorders in developing brains. The trick may be to get adolescents to agree among themselves that drug use is "uncool". This seems to have happened with tobacco, at least in some countries.

    It would be interesting to find out to what extent the different rates of drug and alcohol addiction in different countries reflect differences in the distribution of risk alleles across countries. Cultural differences and government policies will also be factors. To take an extreme example, I'm sure the rate of alcoholism in Saudi Arabia is very low, because the strong cultural and governmental prohibitions on alcohol mean that most people with a genetic predisposition to alcoholism will probably never drink it even once.
    I think that's why the comparison between France and Italy is so interesting. Both are "wine" countries, where it is common to drink it with lunch and dinner. At dinner when I was quite young, I remember being given "baptized" wine, which is to say a half inch of wine in a glass then topped up with sparkling water! Of course the wine had about 4-5% alcohol. It was totally commonplace. Yet, Italy has a significantly lower rate of alcoholism than France.

    So, it's not cultural. It has to be genetic to some extent.

    At family weddings or communions I've seen my father and his six brothers tipsy, but I never saw any of them really drunk. As for the aunts and female cousins, it would be unthinkable. I might have a glass of wine with dinner a few nights a week, or if not that, maybe a liqueur while listening to music before bed, but that's it. Never both. I smoked for four months at university, hated the ashes and the way my fingers and hair and clothes smelled, and just quit. Never missed them, craved them, nothing. As for drugs, I was 19 when I was offered marijuana, again, at university. I hated it, hated the feeling of being out of control, of my mind not being "clear", and never did it again, or any other recreational drug. When I had to have surgery about ten years ago, I told the anesthesiologist to give me the same amount he'd give a Mormon or I'd sleep for a week. :) So, what ever those alleles are, I certainly didn't get them.

    I do remember hearing my father say that the French drank more "hard" alcohol than we did, so the difference was apparent even then. In small villages of my childhood, when you went to the "bar", you could have coffee drinks, aperitifs, digestifs, and wine, maybe a beer, but bottles of "hard" liquor were rarely seen. Also, it was, and among older people probably still is, socially taboo to be drunk in public. It doesn't make for the "bella figura" which is so important in Italian culture. I also remember my father saying a real man never lets himself appear out of control like that. God forbid if it were a woman. The family would never recover. In my family I never saw any of the women take more than a glass of wine with their meals. Old men sometimes indulged too much, but that's about it.

    To some extent things are changing with the very young. They see young drunk tourists, and movies about it, unfortunately.

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    Quote Originally Posted by Angela View Post
    I think that's why the comparison between France and Italy is so interesting. Both are "wine" countries, where it is common to drink it with lunch and dinner. At dinner when I was quite young, I remember being given "baptized" wine, which is to say a half inch of wine in a glass then topped up with sparkling water! Of course the wine had about 4-5% alcohol. It was totally commonplace. Yet, Italy has a significantly lower rate of alcoholism than France.

    So, it's not cultural. It has to be genetic to some extent.

    At family weddings or communions I've seen my father and his six brothers tipsy, but I never saw any of them really drunk. As for the aunts and female cousins, it would be unthinkable. I might have a glass of wine with dinner a few nights a week, or if not that, maybe a liqueur while listening to music before bed, but that's it. Never both. I smoked for four months at university, hated the ashes and the way my fingers and hair and clothes smelled, and just quit. Never missed them, craved them, nothing. As for drugs, I was 19 when I was offered marijuana, again, at university. I hated it, hated the feeling of being out of control, of my mind not being "clear", and never did it again, or any other recreational drug. When I had to have surgery about ten years ago, I told the anesthesiologist to give me the same amount he'd give a Mormon or I'd sleep for a week. :) So, what ever those alleles are, I certainly didn't get them.

    I do remember hearing my father say that the French drank more "hard" alcohol than we did, so the difference was apparent even then. In small villages of my childhood, when you went to the "bar", you could have coffee drinks, aperitifs, digestifs, and wine, maybe a beer, but bottles of "hard" liquor were rarely seen. Also, it was, and among older people probably still is, socially taboo to be drunk in public. It doesn't make for the "bella figura" which is so important in Italian culture. I also remember my father saying a real man never lets himself appear out of control like that. God forbid if it were a woman. The family would never recover. In my family I never saw any of the women take more than a glass of wine with their meals. Old men sometimes indulged too much, but that's about it.

    To some extent things are changing with the very young. They see young drunk tourists, and movies about it, unfortunately.
    If there are genetic differences between the French and Italians that relate to alcohol, I wonder if they date back to the Bell Beaker period? I believe that the French have more steppe-like ancestry than Italians on average. It's only speculation, but those bell beakers seem to have been used to drink alcohol, and since they were prized grave goods, alcohol may have been an important part of their rituals and culture. Heavy drinkers and even alcoholic men may have been rewarded (genetically) by having more children. Being habitually intoxicated may have lowered their inhibitions, making them more likely to want to rape and pillage their neolithic neighbours than their less intoxicated fellow men. It would be easy to reduce them to a violent drunken stereotype, but looking at the maps of Europe, there are similarities in the distributions of alcohol consumption and steppe-like ancestry.

    New Zealand, like Australia, is a "beer" country with a binge drinking problem. Decades ago the government tried to curb the problem by banning the sale of alcohol after 6pm. This led to what was dubbed the "six o'clock swill". Men would finish work, then rush to the bars and drink as much as possible between 5 and 6pm before staggering home to their wives and children. The experiment ended in the 1960s.

    I'm lucky, I also seem to lack the alleles for addiction or drug dependence, so moderation in all things was easy for me. Even when I used cannabis, it was only at night, and I could stop for months without missing it. These days I just have a little wine with dinner most evenings, but I have no interest in getting drunk.

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    I love getting drunk, but I usually prefer getting tipsy and content. I don't get drunk nearly as often as I used to and everything is a-ok with me healthwise, save for an iffy digestive system and heart palpitations (but these issues started before I had my first sip of alcohol)
    mmmmmmmmm dooouuughhhnuuuutz

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    Quote Originally Posted by LecrameMark View Post
    I don't believe in that. What's up with this math??
    I like Cannabis and used it a lot but never liked nicotine or tobacco. Used to smoke cigs many years ago and quit easily.

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