Drug Addiction Erodes 'Free Will' Over Time -- Moran 42 (13): 16 -- Psychiatr News:
"Addiction and the progressive loss of control over behavior that seems to accompany the addictive process are the result of changes in multiple regions of the brain.
[...]
Changes occur initially as a result of the abnormal increase in dopamine that results from use of all drugs of addiction and eventually affect memory and attention, the regulation of impulsivity, and executive function.
What Volkow described is an emerging understanding of addiction and the underlying neurobiology of free will and choice that is vastly more sophisticated than theories that were dominant 15 years ago, when addiction was hypothesized as an overactivation of reward systems in the brain by dopamine.
Instead, what has evolved is a picture of multiple regions of the brain being progressively compromised—the anterior cingulate gyrus, which governs attention and regulation of impulsivity; the orbital prefrontal cortex, which mediates the assignment of value to stimuli in the environment; and the dorsal lateral prefrontal cortex, which governs executive function and decision making.
It is a picture of the destruction of complex, interacting systems corresponding remarkably with the clinical picture of progressive alcoholism and drug addiction: each of these interacting regions of the brain compensate for each other, so that in the early stages, when damage to the brain caused by the pathological increase in dopamine is still relatively minor, the addict may yet assert some control over choices.
Dopamine has been recognized for some time as a key in addiction, the neurochemical that alcohol and all drugs of abuse are known to increase dramatically in the brain. But until recently, it was believed that dopamine acted principally on limbic areas of the brain, associated with reward and pleasure.
Volkow explained that it is not just pleasure, but "saliency"—the brain's perception of stimuli in the environment as vital or important to pay attention to—that dopamine signals. So, natural stimuli, such as food, sex, or money, or aversive stimuli, such as the perception of danger or fear, also increase dopamine in the brain.
But drugs and alcohol are known to be much more potent stimulators, flooding the brain with dopamine at levels that are "supraphysiological" and ultimately destructive to multiple brain regions.
"What drugs are doing is exactly the same thing that nature has generated for us to respond to stimuli in the environment, but the drugs do it in a much more potent way," Volkow said. "It is believed that this large increase in signaling leads to plastic changes in the brain that underlie compulsive drug intake."
Dopamine System Underactivated
Under the earlier conception of dopamine as working primarily on reward centers of the brain, it was believed that addicts were experiencing a greater sense of reward or pleasure. But Volkow described studies from the early 1990s showing that in fact cocaine abusers who were given intravenous methylphenidate—a proxy for cocaine—experienced a less-intense high while also experiencing greater drug craving than control subjects.
Moreover, several studies have documented the surprising fact that cocaine addicts actually have lower levels of dopamine D2 receptors than control subjects, she said. This in turn has led to a new insight—not that addicts are experiencing greater pleasure from drugs of abuse, but that they are actually less sensitive to the effects of dopamine.
And so they seek out drugs because of the very potency with which they can increase dopamine in the brain, often at the expense of other pleasurable natural stimulants that do not increase dopamine so dramatically. And it is the neurobiological reflection of the phenomenon of "diminishing effects" that addicts typically report clinically: they require more and more of the drug to get a similar effect.
"Cocaine-addicted people are not taking the drug because it is more pleasurable," Volkow said. "If anything, it is documented that the sensitivity of the reward system in the brain is in fact decreased. They have a hypofunctional dopaminergic system.
"The person who is addicted starts to seek the drug of abuse because it is powerful enough to activate the system," she said.
Underscoring that insight is research described by Volkow showing that when rats trained to press a lever for alcohol are injected with an adenovirus carrying a D2 receptor, their alcohol consumption is markedly diminished.
But as the addiction progresses with continual administration of the abused drug, all of these brain systems are progressively destroyed, so that in the later stages the individual may seem to lack all power of choice and free will.
"We have come to see addiction as a disease that involves the destruction of multiple systems in the brain that more or less are able to compensate for one another," Volkow said. "When the pathology erodes the various systems, you disrupt the ability to compensate, and the addictive disease erodes and destroys the life of the individual."
Executive Function Damaged
Also corresponding to the clinical picture of addiction is the discovery that dopamine can be released into the brain as a conditioned response to stimuli associated with the drug of abuse. Volkow reported results of a study by her and colleagues published in the June 2006 Journal of Neuroscience in which increases in dopamine in striatal regions of the brain were measured in 18 cocaine users while watching neutral video images of nature, and again when watching video images of people preparing and administering cocaine.
When watching the cocaine cue videos, subjects experienced an increase in dopamine. Moreover, the magnitude of the increase was significantly associated with subjects' self-report of craving.
"They are not taking cocaine—only observing someone taking cocaine," she said. "That by itself is able to increase dopamine in the striatal regions.
"This is ver y important clinically because we know that when patients go into an environment where there are people taking the drug, they react," Volkow added. "This is the essence of the conditioned response, and it makes the treatment of addiction a very tough challenge."
The carnage in the brain wrought by addiction extends as well to the prefrontal cortex, areas of the brain that govern executive function and the ability to change behavior in response to changing circumstances."
"Addiction and the progressive loss of control over behavior that seems to accompany the addictive process are the result of changes in multiple regions of the brain.
[...]
Changes occur initially as a result of the abnormal increase in dopamine that results from use of all drugs of addiction and eventually affect memory and attention, the regulation of impulsivity, and executive function.
What Volkow described is an emerging understanding of addiction and the underlying neurobiology of free will and choice that is vastly more sophisticated than theories that were dominant 15 years ago, when addiction was hypothesized as an overactivation of reward systems in the brain by dopamine.
Instead, what has evolved is a picture of multiple regions of the brain being progressively compromised—the anterior cingulate gyrus, which governs attention and regulation of impulsivity; the orbital prefrontal cortex, which mediates the assignment of value to stimuli in the environment; and the dorsal lateral prefrontal cortex, which governs executive function and decision making.
It is a picture of the destruction of complex, interacting systems corresponding remarkably with the clinical picture of progressive alcoholism and drug addiction: each of these interacting regions of the brain compensate for each other, so that in the early stages, when damage to the brain caused by the pathological increase in dopamine is still relatively minor, the addict may yet assert some control over choices.
Dopamine has been recognized for some time as a key in addiction, the neurochemical that alcohol and all drugs of abuse are known to increase dramatically in the brain. But until recently, it was believed that dopamine acted principally on limbic areas of the brain, associated with reward and pleasure.
Volkow explained that it is not just pleasure, but "saliency"—the brain's perception of stimuli in the environment as vital or important to pay attention to—that dopamine signals. So, natural stimuli, such as food, sex, or money, or aversive stimuli, such as the perception of danger or fear, also increase dopamine in the brain.
But drugs and alcohol are known to be much more potent stimulators, flooding the brain with dopamine at levels that are "supraphysiological" and ultimately destructive to multiple brain regions.
"What drugs are doing is exactly the same thing that nature has generated for us to respond to stimuli in the environment, but the drugs do it in a much more potent way," Volkow said. "It is believed that this large increase in signaling leads to plastic changes in the brain that underlie compulsive drug intake."
Dopamine System Underactivated
Under the earlier conception of dopamine as working primarily on reward centers of the brain, it was believed that addicts were experiencing a greater sense of reward or pleasure. But Volkow described studies from the early 1990s showing that in fact cocaine abusers who were given intravenous methylphenidate—a proxy for cocaine—experienced a less-intense high while also experiencing greater drug craving than control subjects.
Moreover, several studies have documented the surprising fact that cocaine addicts actually have lower levels of dopamine D2 receptors than control subjects, she said. This in turn has led to a new insight—not that addicts are experiencing greater pleasure from drugs of abuse, but that they are actually less sensitive to the effects of dopamine.
And so they seek out drugs because of the very potency with which they can increase dopamine in the brain, often at the expense of other pleasurable natural stimulants that do not increase dopamine so dramatically. And it is the neurobiological reflection of the phenomenon of "diminishing effects" that addicts typically report clinically: they require more and more of the drug to get a similar effect.
"Cocaine-addicted people are not taking the drug because it is more pleasurable," Volkow said. "If anything, it is documented that the sensitivity of the reward system in the brain is in fact decreased. They have a hypofunctional dopaminergic system.
"The person who is addicted starts to seek the drug of abuse because it is powerful enough to activate the system," she said.
Underscoring that insight is research described by Volkow showing that when rats trained to press a lever for alcohol are injected with an adenovirus carrying a D2 receptor, their alcohol consumption is markedly diminished.
But as the addiction progresses with continual administration of the abused drug, all of these brain systems are progressively destroyed, so that in the later stages the individual may seem to lack all power of choice and free will.
"We have come to see addiction as a disease that involves the destruction of multiple systems in the brain that more or less are able to compensate for one another," Volkow said. "When the pathology erodes the various systems, you disrupt the ability to compensate, and the addictive disease erodes and destroys the life of the individual."
Executive Function Damaged
Also corresponding to the clinical picture of addiction is the discovery that dopamine can be released into the brain as a conditioned response to stimuli associated with the drug of abuse. Volkow reported results of a study by her and colleagues published in the June 2006 Journal of Neuroscience in which increases in dopamine in striatal regions of the brain were measured in 18 cocaine users while watching neutral video images of nature, and again when watching video images of people preparing and administering cocaine.
When watching the cocaine cue videos, subjects experienced an increase in dopamine. Moreover, the magnitude of the increase was significantly associated with subjects' self-report of craving.
"They are not taking cocaine—only observing someone taking cocaine," she said. "That by itself is able to increase dopamine in the striatal regions.
"This is ver y important clinically because we know that when patients go into an environment where there are people taking the drug, they react," Volkow added. "This is the essence of the conditioned response, and it makes the treatment of addiction a very tough challenge."
The carnage in the brain wrought by addiction extends as well to the prefrontal cortex, areas of the brain that govern executive function and the ability to change behavior in response to changing circumstances."
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