← In the Realm of Hungry Ghosts Close Encounters with Addiction
In the Realm of Hungry Ghosts Close Encounters with Addiction Chapter 13. A Different State of the Brain
Author: Gabor Mate Publisher: Berkeley, CA: North Atlantic Books. Publish Date: 2010-1-5 Review Date: Status:📚
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CHAPTER 13
A Different State of the Brain
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As we have seen, laboratory animals can be led into drug and alcohol addiction. Hooked up to the appropriate apparatus and allowed unlimited access, many rats will self-administer intravenous cocaine to the point of hunger, exhaustion, and death. Researchers even know how to make some laboratory creatures—rats, mice, monkeys, and apes—more vulnerable to addiction by genetic manipulations or by interference with prenatal and postnatal development. The drug-addicted brain doesn’t work in the same way as the nonaddicted brain, and it doesn’t look the same when imaged by means of positron-emission tomography (PET) scans and magnetic resonance imaging (MRI), two recently developed, sophisticated imaging techniques that are now yielding new information about brain structure and functioning. An MRI study in 2002 looked at the white matter in the brains of dozens of cocaine addicts from youth to middle age, in comparison with the white matter of nonusers. The brain’s gray matter contains the cell bodies of nerve cells; their connecting fibers, covered by fatty white tissue, form the white matter. As we age, we develop more active connections and therefore more white matter. In the brains of cocaine addicts the age-related expansion of white matter is absent.3 Functionally, this means a loss of learning capacity—a diminished ability to make new choices, acquire new information, and adapt to new circumstances. It gets worse. Other studies have shown that gray matter density, too, is reduced in the cerebral cortex of cocaine addicts—that is, they have smaller or fewer nerve cells than is normal. A diminished volume of gray matter has also been shown in heroin addicts and alcoholics, and this reduction in brain size is correlated with the years of use: the longer the person has been addicted, the greater the loss of volume.4 In the part of the cerebral cortex responsible for regulating emotional impulses and for making rational decisions, addicted brains have reduced activity. In special scanning studies these brain centers have also exhibited diminished energy utilization in chronic substance users, indicating that the nerve cells and circuits in those locations are doing less work. When tested psychologically, these same addicts showed impaired functioning of their prefrontal cortex, the “executive” part of the human brain. Thus, the impairments of physiological function revealed through imaging were paralleled by a diminished capacity for rational thought. In animal studies, reduced nerve cell counts, altered electrical activity, and abnormal nerve cell branching in the brain were found after chronic cocaine use.5 Similarly, altered structure and branching of nerve cells has been seen after long-term opiate administration and also with chronic nicotine use.6 Such changes are sometimes reversible but can last for a long time and may even be lifelong, depending on the duration and intensity of drug use.
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G. Bartzokis et al., “Brain Maturation May Be Arrested in Chronic Cocaine Addicts,” Biological Psychiatry 5(8) (April 2002): 605–11
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R. Z. Goldstein and N. D. Volkow, “Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex,” American Journal of Psychiatry 159 (2002): 1642–52.
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Charles A. Dackis, “Recent Advances in the Pharmacotherapy of Cocaine Dependence,” Current Psychiatry Reports 6 (2004): 323–31.
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T. E. Robinson and B. Kolb, “Structural Plasticity Associated with Exposure to Drugs of Abuse,” Neuropharmacology 27 (2004): 33–56.
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To write about the biology of addiction one must write about dopamine, a key brain chemical “messenger” that plays a central role in all forms of addiction. An imaging study of rhesus monkeys published in 2006 confirmed previous findings that the number of receptors for dopamine was reduced in chronic cocaine users.7 Receptors are the molecules on the surfaces of cells where chemical messengers fit and influence the activity of the cell. Every cell membrane holds many thousands of receptors for many types of messenger molecules. Cells receive input and direction from other parts of the brain and the body and from the outside by means of messenger-receptor interactions. If it wasn’t for their ability to exchange messages with their environment, cells could not function. Cocaine and other stimulant-type drugs work because they greatly increase the amount of dopamine available to cells in essential brain centers. That sudden rise in the levels of dopamine, one of the brain’s “feel-good” chemicals, accounts for the elation and sense of infinite potential experienced by the stimulant user, at least at the beginning of the drug habit. As mentioned, it was already known that the brains of chronic cocaine users had fewer than normal dopamine receptors. The fewer such receptors, the more the brain would “welcome” external substances that could help increase its available dopamine supply. This recent primate study showed for the first time that the monkeys who developed a higher rate of cocaine self-administration—the ones who became more hard-core users—had a lower number of these receptors to begin with, before ever having been exposed to the chemical. This illuminating finding suggests that among rhesus monkeys, who are considered to be excellent models of human addiction, some are much more prone to extremes of drug dependence than are others.
- M. A. Nader et al., “PET Imaging of Dopamine D2 Receptors during Chronic Cocaine Self-administration in Monkeys,” Nature Neuroscience 8 (August 9, 2006).
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Stimulant drugs like cocaine and methamphetamine (crystal meth) exert their effect by making more dopamine available to cells that are activated by this brain chemical. Because dopamine is important for motivation, incentive, and energy, a diminished number of receptors will reduce the addict’s stamina and his incentive and drive for normal activities when not using the drug. It’s a vicious cycle: more cocaine use leads to more loss of dopamine receptors. The fewer receptors, the more the addict needs to supply his brain with an artificial chemical to make up for the lack.
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Why does chronic self-administration of cocaine reduce the density of dopamine receptors? It’s a simple matter of brain economics. The brain is accustomed to a certain level of dopamine activity. If it is flooded with artificially high dopamine levels, it seeks to restore the equilibrium by reducing the number of receptors where the dopamine can act. This mechanism helps to explain the phenomenon of tolerance, by which the user has to inject, ingest, or inhale higher and higher doses of a substance to get the same effect as before. If deprived of the drug, the user goes into withdrawal partly because the diminished number of receptors can no longer generate the required normal dopamine activity: hence the irritability, depressed mood, alienation, and extreme fatigue of the stimulant addict without his drug: this is the physical dependence state discussed in Chapter Eleven. It can take months or longer for the receptor numbers in the brain to rise back to pre-drug use figures.
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On the cellular level addiction is all about neurotransmitters and their receptors. In different ways, all commonly abused drugs temporarily enhance the brain’s dopamine functioning. Alcohol, marijuana, the opiates heroin and morphine, and stimulants such as nicotine, caffeine, cocaine, and crystal meth all have this effect. Cocaine, for example, blocks the reuptake, or reentry, of dopamine into the nerve cells from which it is originally released. Like all neurotransmitters, dopamine does its work in the space between cells, known as the synaptic space, or cleft. A synapse is where the branches of two nerve cells converge without touching, and it’s in the space between them that messages are chemically transmitted from one cell to the next. That is why the brain needs chemical messengers, or neurotransmitters, to function. Released from a neuron, or nerve cell, a neurotransmitter such as dopamine “floats” across the synaptic space and attaches to receptors on a second neuron. Having carried its message to the target nerve cell, the molecule then falls back into the synaptic cleft, and from there it is taken back up into the originating neuron for later reuse—hence the term reuptake. The greater the reuptake, the less neurotransmitter remains active between the neurons.
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Cocaine’s action may be likened to that of the antidepressant fluoxetine (Prozac). Prozac belongs to a family of drugs that increase the levels of the mood-regulating neurotransmitter serotonin between nerve cells by blocking its reuptake. They’re called selective serotonin reuptake inhibitors, or SSRIs. Cocaine, one might say, is a dopamine reuptake inhibitor. It occupies the receptor on the cell surface normally used by the brain chemical that would transport dopamine back into its source neuron. In effect, cocaine is a temporary squatter in someone else’s home. The more of these sites occupied by cocaine, the more dopamine remains in the synaptic space and the greater the euphoria reported by the user.8 Unlike Prozac, cocaine is not selective: it also inhibits the reuptake of other messenger molecules, including serotonin. By contrast, nicotine directly triggers dopamine release from cells into the synaptic space. Crystal meth both releases dopamine, like nicotine, and blocks its reuptake, like cocaine. The power of crystal meth to rapidly multiply dopamine levels is responsible for its intense euphoric appeal. These stimulants directly increase dopamine levels, but the action of some chemicals on dopamine is indirect. Alcohol, for example, reduces the inhibition of dopamine-releasing cells. Narcotics like morphine act on natural opiate receptors on cell surfaces to trigger dopamine discharge.9
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N. D. Volkow et al., “Relationship between Subjective Effects of Cocaine and Dopamine Transporter Occupancy,” Nature 386(6627) (April 1997): 827–30.
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G. F. Koob, “Drugs of Abuse: Anatomy, Pharmacology, and Function of Reward Pathways,” Trends in Pharmacological Science 13(5) (May 1992): 177–84.
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Activities such as eating or sexual contact also promote the presence of dopamine in the synaptic space. Dr. Richard Rawson, associate director of the University of California, Los Angeles’s Integrated Substance Abuse Program, reports that food seeking can increase brain dopamine levels in some key brain centers by 50 percent. Sexual arousal will do so by a factor of 100 percent, as will nicotine and alcohol. But none of these can compete with cocaine, which more than triples dopamine levels. Yet cocaine is a miser compared with crystal meth, or “speed,” whose dopamine-enhancing effect is an astounding 1,200 percent.10 It’s easy to see why Carol, the woman addicted to crystal meth, spoke of the drug’s effect as an “orgasm without sex.” After repeated crystal meth use the number of dopamine receptors in crucial brain circuits will be reduced, just as with cocaine.
- Dr. Richard Rawson, associate director of the Integrated Substance Abuse Program, University of California, Los Angeles, Teleconference, April 26, 2006. Available from U.S. Consulate, Vancouver, BC.
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In short, drug use temporarily changes the brain’s internal environment: the “high” is produced by means of a rapid chemical shift. There are also long-term consequences: chronic drug use remodels the brain’s chemical structure, its anatomy, and its physiological functioning. It even alters the way the genes act in the nuclei of brain cells. “Among the most insidious consequences to drugs of abuse is the vulnerability to craving and relapse after many weeks or years of abstinence,” says a review of addiction neurobiology in a psychiatric journal. “The enduring nature of this behavioral vulnerability implies long-lasting changes in brain function.”11 Since the brain determines the way we act, these biological changes lead to altered behaviors. It is in this sense that medical language refers to addiction as a chronic disease, and it is in this sense of a drug-affected brain state that I think the disease model is useful. It may not fully define addiction, but it does help us understand some of its most important features.
- P. W. Kalivas, “Recent Understanding in the Mechanisms of Addiction,” Current Psychiatry Reports 6 (2004): 347–51.
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In any disease, say smoking-induced lung or heart disease, organs and tissues are damaged and function in pathological ways. When the brain is diseased, the functions that become pathological are the person’s emotional life, thought processes, and behavior. And this creates addiction’s central dilemma: if recovery is to occur, the brain, the impaired organ of decision making, needs to initiate its own healing process. An altered and dysfunctional brain must decide that it wants to overcome its own dysfunction: to revert to normal—or, perhaps, become normal for the very first time. The worse the addiction is, the greater the brain abnormality and the greater the biological obstacles to opting for health. The scientific literature is nearly unanimous in viewing drug addiction as a chronic brain condition, and this alone ought to discourage anyone from blaming or punishing the sufferer. No one, after all, blames a person suffering from rheumatoid arthritis for having a relapse, since relapse is one of the characteristics of chronic illness. The very concept of choice appears less clear-cut if we understand that the addict’s ability to choose, if not absent, is certainly impaired. “The evidence for addiction as a different state of the brain has important treatment implications,” writes Dr. Charles O’Brien. “Unfortunately,” he adds, “most health care systems continue to treat addiction as an acute disorder, if at all.”