Ham-milton
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An article appears in the May 2008 edition of Scientific American written by Dr. Joseph DiFranza detailing his research that indicates it is indeed possible to become addicted (experience withdrawal symptoms) after the very first smoke. Most of this research was conducted on adolescents who are seemingly more prone to addiction and rats, while other research, especially on quitting, was conducted on abstaining adults. I've taken the time to go through this article and condense and paraphrase parts to make it more readable for the internet. I don't typically put much stock into the one-hit addiction theories, but this one seems to have ample evidence behind it, at least that withdrawal symptoms can be experienced after that first smoke.
Development of Addiction
From the begining of the understanding of nicotine addiction until quite recently, nicotine addiction was thought to only begin when a constant level of nicotine was maintained in the blood- roughly when five cigarettes are smoked per day. For many, this begins after years, leading scientists to believe that nicotine addiction was a relatively difficult thing to acquire.
Unfortunately, even then, this was nothing more than an educated guess.
Dr. Joseph R. DiFranza and colleagues at the University of Massachussetts Medical School in Worcester have gone long ways to drastically alter this thinking.
For a change, the 1-use Addiction theory actually has scientific grounding, at least for nicotine addiction.
I'm not going to go through and document each point, if you're interested you can search out related references or go and pick up a copy of the most current (May 2008 ) issue of Scientific American and turn to page 82. Despite being a cover story, it's not listed in the Table of Contents for some reason.
DiFranza created the Hooked on Nicotine Checklist or HONC (phonetically HONK if it's easier) with the following questions:
From the day the first cigarette is smoked to the time that a smoker will begin answering "yes" to at least one of the above questions generally occurs within 30 days. Because answering yes to any of these questions indicates that neuronal changes indicating a predisposition to addiction have likely already begun, this makes it very useful for researching addiction.
A large study of adolescent smokes conducted by Jennifer O'Loughlin at McGill University, Denise Kandel at Columbia University and Robert Scragg at the University of Auckland in New Zealand found that of those who experience withdrawal symptoms, 10 percent do so within two days of their first cigarette, and 25-35 within the first month. In an expansive study of New Zealand adolescent smokers, answering "yes" on the HONC questionaire found a 200% increase in the likelihood that they would progress to daily smoking.
The previous theory of Nicotine Addiction said that nicotine caused pleasure and that smokers continued to smoke because of an urge to re-experience that pleasure. This was not backed up by the fact that most smokers reported lessening pleasure as their addiction worsened and they had been smoking longer.
DiFranza theorized that nicotine, while causing pleasure at first, did less to stimulate the craving-generation system (as very euphoric drugs with direct action on dopamine are though to, such as Cocaine), but rather that it inhibits the craving-inhibition system. Because the brain adapts or sensitizes to this inhibited inhibition-system, when nicotine is removed from the equation- as it is during withdrawal- the craving generation system (whose effect has been increased to adapt to the increased weight of the craving inhibition system) is suddenly able to overpower the craving generation system.
This adequately explains why a drug that is not nearly as euphoric as most drugs of abuse, and doesn't create the social maladaptations seen with heroin or cocaine, is as difficult to quit for many people.
Research in animals and human cadavers have shown that nicotinic receptors proliferate when nicotine is administered between 50 and 100 percent in the frontal lobe, hippocampus and cerebellum. Animals for these studies were administered roughly the equivalent of four to five packs of cigarettes per day.
More recently, research has been conducted by Theodore Slotkin at Duke University looking for the minimal level of nicotine administration needed to produce upregulation of nicotinic ACh receptors. Slotkin found that administering the equivalent of one to two cigarettes of nicotine per day, for two consecutive days was enough to produce upregulation of these receptors in the hippocampus.
Later, Arthur Brody and colleagues at UCLA found that one cigarette's worth of nicotine is enough to occupy up to 88% of nicotine receptors in the brain.
To date there has been no conclusive research on what effect receptor up-regulation means for addiction, but this research does give a plausible physiologic mechanism for withdrawal symptoms after just two days of smoking.
Another study on rat brains found that on the first dose of nicotine, color on an fMRI (indicating metabolism of nicotine) were fairly sparse, but by the fifth dose large chunks of yellow and widespread red (yellow being more intense) blotches. This indicates that brain adaptations develop very rapidly.
Life After Nicotine
Reasoning that after a nicotine addiction, and taking into account that the brain exhibits a substantial degree of plasticity in developing addiction, the sensitization-homeostasis theory would predict an eventual 'remodeling' of brain architecture to acheive homeostasis in life without nicotine. If it did not, there was no decent way to explain why former smokers did not experience horrible lifelong cravings for the drug.
DiFranza concluded that because of these adaptations, a former smoker's brain would look like neither the brain of a smoker or a nonsmoker.
Testing this prediction, Slotkin and colleagues examined rat brains at the four major times of nicotine addiction (before and during exposure, during acute withdrawal and long after withdrawal). They found clear evidence of changes in the functioning of neurons in the brain's cortex and that employs ACh and SE to transmit signals- and that these changes only appeared long after the acute withdrawal phase.
The brains of these 'ex-smoker' rats showed unique adaptations that were not present in the smokers or non-smokers.
HeeJin Lim at the College of Medicine at the Catholic University of Korea found evidence that brain remodeling in humans who quit smoking by studying brain-derived neurotrophic factor, which stimulates neuroplasticity. Levels of this factor increases three times by two months of abstinence.
Thus, abstinence-related adaptations seem to counter the tolerance-related adaptations by inhibiting the craving-generationsystem so that it eventually stops compelling the former smoker to light up. Smoking cues in the environment might still provoke craving, however, and if the long-abstinent smoker were to surrender to the urge to smoke, just once, nicotine would again produce a profound suppression of activity in the craving-generation system. The abstinence related adaptations would then make a bad situation worse. Because these adaptations mimic the effect of nicotine, they would need to be removed to restore homeostasis; when the effect of nicotine wears off, the tolerance-related adaptations would be left unopposed in stimulating the craving, the relapsing smoker would need to puff six to seven cigarettes a day to keep it under control.
Development of Addiction
From the begining of the understanding of nicotine addiction until quite recently, nicotine addiction was thought to only begin when a constant level of nicotine was maintained in the blood- roughly when five cigarettes are smoked per day. For many, this begins after years, leading scientists to believe that nicotine addiction was a relatively difficult thing to acquire.
Unfortunately, even then, this was nothing more than an educated guess.
Dr. Joseph R. DiFranza and colleagues at the University of Massachussetts Medical School in Worcester have gone long ways to drastically alter this thinking.
For a change, the 1-use Addiction theory actually has scientific grounding, at least for nicotine addiction.
I'm not going to go through and document each point, if you're interested you can search out related references or go and pick up a copy of the most current (May 2008 ) issue of Scientific American and turn to page 82. Despite being a cover story, it's not listed in the Table of Contents for some reason.
DiFranza created the Hooked on Nicotine Checklist or HONC (phonetically HONK if it's easier) with the following questions:
From the day the first cigarette is smoked to the time that a smoker will begin answering "yes" to at least one of the above questions generally occurs within 30 days. Because answering yes to any of these questions indicates that neuronal changes indicating a predisposition to addiction have likely already begun, this makes it very useful for researching addiction.
A large study of adolescent smokes conducted by Jennifer O'Loughlin at McGill University, Denise Kandel at Columbia University and Robert Scragg at the University of Auckland in New Zealand found that of those who experience withdrawal symptoms, 10 percent do so within two days of their first cigarette, and 25-35 within the first month. In an expansive study of New Zealand adolescent smokers, answering "yes" on the HONC questionaire found a 200% increase in the likelihood that they would progress to daily smoking.
The previous theory of Nicotine Addiction said that nicotine caused pleasure and that smokers continued to smoke because of an urge to re-experience that pleasure. This was not backed up by the fact that most smokers reported lessening pleasure as their addiction worsened and they had been smoking longer.
DiFranza theorized that nicotine, while causing pleasure at first, did less to stimulate the craving-generation system (as very euphoric drugs with direct action on dopamine are though to, such as Cocaine), but rather that it inhibits the craving-inhibition system. Because the brain adapts or sensitizes to this inhibited inhibition-system, when nicotine is removed from the equation- as it is during withdrawal- the craving generation system (whose effect has been increased to adapt to the increased weight of the craving inhibition system) is suddenly able to overpower the craving generation system.
This adequately explains why a drug that is not nearly as euphoric as most drugs of abuse, and doesn't create the social maladaptations seen with heroin or cocaine, is as difficult to quit for many people.
Image Adapted from Scientific American May 2008, Sidebar, page 84
Research in animals and human cadavers have shown that nicotinic receptors proliferate when nicotine is administered between 50 and 100 percent in the frontal lobe, hippocampus and cerebellum. Animals for these studies were administered roughly the equivalent of four to five packs of cigarettes per day.
More recently, research has been conducted by Theodore Slotkin at Duke University looking for the minimal level of nicotine administration needed to produce upregulation of nicotinic ACh receptors. Slotkin found that administering the equivalent of one to two cigarettes of nicotine per day, for two consecutive days was enough to produce upregulation of these receptors in the hippocampus.
Later, Arthur Brody and colleagues at UCLA found that one cigarette's worth of nicotine is enough to occupy up to 88% of nicotine receptors in the brain.
To date there has been no conclusive research on what effect receptor up-regulation means for addiction, but this research does give a plausible physiologic mechanism for withdrawal symptoms after just two days of smoking.
Another study on rat brains found that on the first dose of nicotine, color on an fMRI (indicating metabolism of nicotine) were fairly sparse, but by the fifth dose large chunks of yellow and widespread red (yellow being more intense) blotches. This indicates that brain adaptations develop very rapidly.
Life After Nicotine
Reasoning that after a nicotine addiction, and taking into account that the brain exhibits a substantial degree of plasticity in developing addiction, the sensitization-homeostasis theory would predict an eventual 'remodeling' of brain architecture to acheive homeostasis in life without nicotine. If it did not, there was no decent way to explain why former smokers did not experience horrible lifelong cravings for the drug.
DiFranza concluded that because of these adaptations, a former smoker's brain would look like neither the brain of a smoker or a nonsmoker.
Testing this prediction, Slotkin and colleagues examined rat brains at the four major times of nicotine addiction (before and during exposure, during acute withdrawal and long after withdrawal). They found clear evidence of changes in the functioning of neurons in the brain's cortex and that employs ACh and SE to transmit signals- and that these changes only appeared long after the acute withdrawal phase.
The brains of these 'ex-smoker' rats showed unique adaptations that were not present in the smokers or non-smokers.
HeeJin Lim at the College of Medicine at the Catholic University of Korea found evidence that brain remodeling in humans who quit smoking by studying brain-derived neurotrophic factor, which stimulates neuroplasticity. Levels of this factor increases three times by two months of abstinence.
Thus, abstinence-related adaptations seem to counter the tolerance-related adaptations by inhibiting the craving-generationsystem so that it eventually stops compelling the former smoker to light up. Smoking cues in the environment might still provoke craving, however, and if the long-abstinent smoker were to surrender to the urge to smoke, just once, nicotine would again produce a profound suppression of activity in the craving-generation system. The abstinence related adaptations would then make a bad situation worse. Because these adaptations mimic the effect of nicotine, they would need to be removed to restore homeostasis; when the effect of nicotine wears off, the tolerance-related adaptations would be left unopposed in stimulating the craving, the relapsing smoker would need to puff six to seven cigarettes a day to keep it under control.
