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← In the Realm of Hungry Ghosts Close Encounters with Addiction

In the Realm of Hungry Ghosts Chapter 18. Trauma, Stress, and the Biology of Addiction

Author: Gabor Mate Publisher: Berkeley, CA: North Atlantic Books. Publish Date: 2010-1-5 Review Date: 2023-1-12 Status:📚

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The three dominant brain systems in addiction—the opioid attachment-reward system, the dopamine-based incentive-motivation apparatus, and the self-regulation areas of the prefrontal cortex—are all exquisitely fine-tuned by the environment. To various degrees, in all addicted persons these systems are out of kilter. The same is true, we will see, of the fourth brain-body system implicated in addiction: the stress-response mechanism. Happy, attuned emotional interactions with parents stimulate a release of natural opioids in an infant’s brain. This endorphin surge promotes the attachment relationship and the further development of the child’s opioid and dopamine circuitry.1 On the other hand, stress reduces the numbers of both opiate and dopamine receptors. Healthy growth of these crucial systems—responsible for such essential drives as love, connection, pain relief, pleasure, incentive, and motivation—depends, therefore, on the quality of the attachment relationship. When circumstances do not allow the infant and young child to experience consistently secure interactions or, worse, expose him to many painfully stressing ones, maldevelopment often results.

  1. A. N. Schore, Affect Regulation and the Origin of the Self (Hillsdale, NJ: Lawrence Erlbaum Associates, 1994), 142.

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We know from animal studies that social-emotional stimulation is necessary for the growth of the nerve endings that release dopamine and for the growth of receptors to which dopamine needs to bind in order to do its work. Even adult rats and mice kept in long-term isolation will have a reduced number of dopamine receptors in the midbrain incentive circuits and, notably, in the frontal areas implicated in addiction.3 Rats separated from their mothers at an early stage display permanent disruption of the dopamine incentive-motivation system in their midbrains. As we already know, abnormalities in this system play a key role in the onset of addiction and craving. Predictably, in adulthood these maternally deprived animals exhibit a greater propensity to self-administer cocaine.4 And it doesn’t take extreme deprivation: in another study, rat pups deprived of their mother’s presence for only one hour a day during their first week of life grew up to be much more eager than their peers to take cocaine on their own.5 So the presence of consistent parental contact in infancy is one factor in the normal development of the brain’s neurotransmitter systems; the absence of it makes the child more vulnerable to “needing” drugs of abuse later on to supplement what her own brain is lacking. Another key factor is the quality of the contact the parent provides, and this, as we saw in the previous chapter, depends very much on the parent’s mood and stress level.

  1. G. Blanc et al., “Response to Stress of Mesocortico-Frontal Dopaminergic Neurons in Rats after Long-Term Isolation,” Nature 284 (March 20, 1980): 265–67.

  2. M. J. Meaney et al., “Environmental Regulation of the Development of Mesolimbic Dopamine Systems: A Neurobiological Mechanism for Vulnerability to Drug Abuse?” Psychoneuroendocrinology 27 (2002): 127–38.

  3. Harold H. Gordon, “Early Environmental Stress and Biological Vulnerability to Drug Abuse,” Psychoneuroendocrinology 27 (2002): 115–26.

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All mammalian mothers—and many human fathers, as well—give their infants sensory stimulation that has long-term positive effects on their offspring’s brain chemistry. Such sensory stimulation is so necessary for the human infant’s healthy biological development that babies who are never picked up simply die. They stress themselves to death. Premature babies who have to live in incubators for weeks or months have faster brain growth if they are stroked for just ten minutes a day. When I learned such facts in the research literature, I recalled with appreciation a custom I had often observed among my Indo-Canadian patients during my years in family practice. As they were speaking with me during their early postnatal visits, these mothers would massage their babies all over their bodies, gently kneading them from feet to head. The infants were in bliss.

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Humans hold and cuddle and stroke; rats lick. A 1998 study found that rats whose mothers had given them more licking and other kinds of nurturing contact during their infancy had, as adults, more efficient brain circuitry for reducing anxiety. They also had more receptors on their nerve cells for benzodiazepines, which are natural tranquilizing chemicals found in the brain.6 I think here of my many patients who, on top of cocaine and heroin addictions, have been hooked since their adolescence on street-peddled “benzo” drugs like Valium to calm their jangled nervous systems. For a dollar a tablet, they get an artificial hit of the benzodiazepines their own brains can’t supply. Their need for tranquilizers says much about their infancy and early childhood.

  1. C. Caldji et al., “Maternal Care During Infancy Regulates the Development of Neural Systems Mediating the Expression of Fearfulness in the Rat,” Neurobiology 95(9) (April 28, 1998): 5335–40.

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Parental nurturing determines the levels of other key brain chemicals, too—including serotonin, the mood messenger enhanced by anti-depressants like Prozac. Peer-reared monkeys separated from their mothers in laboratory experiments have lower lifelong levels of serotonin than do monkeys brought up by their mothers. In adolescence these same monkeys are more aggressive and are far more likely to consume alcohol in excess.7 We see similar effects with other neurotransmitters that are essential in regulating mood and behavior, such as norepinephrine.8 Even slight imbalances in the availability of these chemicals are manifested in aberrant behaviors such as fearfulness and hyperactivity and increase the individual’s sensitivity to stressors for a lifetime. In turn, such acquired traits increase the risk of addiction.

  1. J. D. Higley and M. Linnoila, “Low Central Nervous System Serotonergic Activity Is Traitlike and Correlates with Impulsive Behavior,” Annals of the New York Academy of Science 836 (December 29, 1997): 39.

  2. A. S. Clarke et al., “Rearing Experience and Biogenic Amine Activity in Infant Rhesus Monkeys,” Biological Psychiatry 40(5) (September 1, 1996): 338–52; see also J. D. Higley et al., “Nonhuman Primate Model of Alcohol Abuse: Effects of Early Experience, Personality, and Stress on Alcohol Consumption,” Proceedings of the National Academy of Sciences USA 88 (August 1991): 7261–65.

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Another effect of early maternal deprivation appears to be a permanent decrease in the production of oxytocin, which, as mentioned in Chapter Fourteen, is one of our love chemicals.9 (As noted earlier, oxytocin is not an opioid. Therefore, it has no relationship whatsoever with narcotic drugs like Oxycet or OxyContin; only the names are similar.) It is critical to our experience of loving attachments and even to maintaining committed relationships. People who have difficulty forming intimate relationships are at risk for addiction; they may turn to drugs as social lubricants.

  1. Martin H. Teicher, “Wounds That Time Won’t Heal: The Neurobiology of Child Abuse,” Cerebrum: The Dana Forum on Brain Science 2(4) (fall 2000).

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Not only can early childhood experience lead to a dearth of “good” brain chemicals; it can also result in a dangerous overload of others. Maternal deprivation and other types of adversity during infancy and childhood result in chronically high levels of the stress hormone cortisol. In addition to damaging the midbrain dopamine system, excess cortisol shrinks important brain centers such as the hippocampus—a structure important for memory and for the processing of emotions—and disturbs normal brain development in many other ways, with lifelong repercussions.10 Another major stress chemical that’s permanently overproduced after insufficient early maternal contact is vasopressin, which is implicated in high blood pressure.11

  1. A. de Mello A et al., “Update on Stress and Depression: The Role of the Hypothalamic-Pituitary-Adrenal (HPA) Axis,” Revista Brasileiva de Psiquiatria 25(4) (October 2003); see also G. W. Kraemer et al., “A Longitudinal Study of the Effect of Different Social Rearing Conditions on Cerebrospinal Fluid Norepinephrine and Biogenic Amine Metabolites in Rhesus Monkeys,” Neuropsychopharmacology 2(3) (September 1989): 175–89.

  2. Teicher, “Wounds That Time Won’t Heal.”

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A child’s capacity to handle psychological and physiological stress is completely dependent on the relationship with his parent or parents. Infants have no ability to regulate their own stress apparatus, and that’s why they will stress themselves to death if they are never picked up. We acquire that capacity gradually as we mature—or we don’t, depending on our childhood relationships with our caregivers. A responsive, predictable nurturing adult plays a key role in the development of our healthy stress-response neurobiology.12

  1. B. Perry and R. Pollard, “Homeostasis, Stress, Trauma, and Adaptation: A Neurodevelopmental View of Childhood Trauma,” Child and Adolescent Clinics of North America 7(1) (January 1998): 33–51.

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(Note that in the human context, “maternal” does not necessarily refer to a female mothering figure or to a biological parent. It can also refer to primary caregivers of either gender.) Children who suffer disruptions in their attachment relationships will not have the same biochemical milieu in their brains as will their well-attached and well-nurtured peers. As a result their experiences and interpretations of their environment, and their responses to it, will be less flexible, less adaptive, and less conducive to health and maturity. Their vulnerability both to the mood-enhancing effects of drugs and to drug dependency will increase. We know from animal studies, for example, that early weaning can have an influence on later substance intake: rat pups weaned from their mothers at two weeks of age had, as adults, a greater propensity to drink alcohol than did pups weaned just one week later.14

  1. L. A. Pohorecky, “Interaction of Ethanol and Stress: Research with Experimental Animals; An Update,” Alcohol and Alcoholism 25(2/3) (1990): 263–76.

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We know something about how specific kinds of childhood trauma affect brain development. For example: the vermis, a part of the cerebellum at the back of the brain, is thought to play a key role in addictions because it influences the dopamine system in the midbrain. Imaging of this structure in adults who were sexually abused as children reveals abnormalities of blood flow, and these abnormalities are associated with symptoms that increase the risk for substance addiction.18 In one study of the EEGs of adults who had suffered sexual abuse, the vast majority had abnormal brain waves, and over a third showed seizure activity.19

  1. C. M. Anderson et al., “Abnormal T2 Relaxation Time in the Cerebellar Vermis of Adults Sexually Abused in Childhood: Potential Role of the Vermis in Stress-Enhanced Risk for Drug Abuse,” Psychoneuroendocrinology 27 (2002): 231–44.

  2. Teicher, “Wounds That Time Won’t Heal.”

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It gets worse. The brains of mistreated children have been shown to be smaller than normal by 7 or 8 percent, with below-average volumes in multiple brain areas, including in the impulse-regulating prefrontal cortex; in the corpus callosum (CC), the bundle of white matter that connects and integrates the functioning of the two sides of the brain; and in several structures of the limbic or emotional apparatus, whose dysfunctions greatly increase vulnerability to addiction.20 In a study of depressed women who had been abused in childhood, the hippocampus (the memory and emotional hub) was found to be 15 percent smaller than normal. The key factor was abuse, not depression, since the same brain area was unaffected in depressed women who had not been abused.21

  1. M. D. De Bellis et al., “Developmental Traumatology Part I: Biological Stress Systems,” Biological Psychiatry 45 (1999): 1271–84.

  2. M. Vythilingam et al., “Childhood Trauma Associated with Smaller Hippocampal Volume in Women with Major Depression,” American Journal of Psychiatry 159: 2072–80.

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I mentioned abnormalities in the CC, which facilitates the collaboration between the brain’s two halves, or hemispheres. Not only have the CCs of trauma survivors been shown to be smaller, but there is evidence of a disruption of functioning there as well. The result can be a “split” in the processing of emotion: the two halves may not work in tandem, particularly when the individual is under stress. One characteristic of personality disorder, a condition with which substance abusers are very commonly diagnosed, is a kind of flip-flopping between idealization of another person and intense dislike, even hatred. There is no middle ground, where both the positive and the negative qualities of the other are acknowledged and accepted.

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Dr. Martin Teicher, director of the Developmental Biopsychiatry Research Program at McLean Hospital in Massachusetts, suggests the very intriguing possibility that our “negative” views of a person are stored in one hemisphere and our “positive” responses in the other. The lack of integration between the two halves of the brain would mean that information from the two views, negative and positive, is not melded into one complete picture. As a result, in intimate relationships and in other areas of life, the afflicted individual fluctuates between idealized and degraded perceptions of himself, other people, and the world.22 This sensible theory, if proven, would explain a lot not only about drug-dependent persons but also about many behavioral addicts.

  1. Teicher, “Wounds That Time Won’t Heal.”

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Of course, the moods and perceptions of my drug-addicted patients swing on pendulums far wilder and more erratic than mine. To some extent these extreme oscillations must be drug induced, but they also reflect the faulty brain dynamics that resulted from my patients’ uniformly miserable childhood histories. Extreme circumstances breed extremist brains.

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Stress is a physiological response mounted by an organism when it is confronted with excessive demands on its coping mechanisms, whether biological or psychological. It is an attempt to maintain internal biological and chemical stability, or homeostasis, in the face of these excessive demands. The physiological stress response involves nervous discharges throughout the body and the release of a cascade of hormones, chiefly adrenaline and cortisol. Virtually every organ is affected, including the heart and lungs, the muscles, and, of course, the emotional centers in the brain. Cortisol itself acts on the tissues of almost every part of the body—from the brain to the immune system, from the bones to the intestines. It is an important part of the infinitely intricate system of checks and balances that enables the body to respond to a threat. At a conference in 1992 at the U.S. National Institutes of Health, researchers defined stress “as a state of disharmony or threatened homeostasis.”23 According to such a definition, a stressor “is a threat, real or perceived, that tends to disturb homeostasis.”24 What do all stressors have in common? Ultimately they all represent the absence of something that the organism perceives as necessary for survival—or its threatened loss. The threat itself can be real or perceived. The threatened loss of a food supply is a major stressor. So is the threatened loss of love—for human beings. “It may be said without hesitation that for man the most important stressors are emotional,” wrote the pioneering Canadian stress researcher and physician Hans Selye.25

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Early stress establishes a lower set point for a child’s internal stress system: such a person becomes stressed more easily than normal throughout her life. Dr. Bruce Perry is senior fellow at the Child Trauma Academy in Houston, Texas, and the former director of Provincial Programs for Children’s Mental Health in Alberta. As he points out, “A child who is stressed early in life will be more overactive and reactive. He is triggered more easily, is more anxious and distressed. Now, compare a person—child, adolescent, or adult—whose baseline arousal is normal with another whose baseline state of arousal is at a higher level. Give them both alcohol: both may experience the same intoxicating effect, but the one who has this higher physiological arousal will have the added effect of feeling pleasure from the relief of that stress. It’s similar to when with a parched throat you drink some cool water: the pleasure effect is much heightened by the relief of thirst.”26

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The hormone pathways of sexually abused children are chronically altered.27 Even a relatively “mild” stressor such as maternal depression—let alone neglect, abandonment, or abuse—can disturb an infant’s physical stress mechanisms.28 Add neglect, abandonment, or abuse, and the child will be more reactive to stress throughout her life. A study published in the Journal of the American Medical Association concluded that “a history of childhood abuse per se is related to increased neuroendocrine [nervous and hormonal] stress reactivity, which is further enhanced when additional trauma is experienced in adulthood.”29

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A brain preset to be easily triggered into a stress response is likely to assign a high value to substances, activities, and situations that provide short-term relief. It will have less interest in long-term consequences, just as people in extremes of thirst will greedily consume water knowing that it may contain toxins.

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On the other hand, situations or activities that for the average person are likely to bring satisfaction are undervalued because, in the addict’s life, they have not been rewarding—for example, intimate connections with family. This shrinking from normal experience is also an outcome of early trauma and stress, as summarized in a recent psychiatric review of child development: Neglect and abuse during early life may cause bonding systems to develop abnormally and compromise capacity for rewarding interpersonal relationships and commitment to societal and cultural values later in life. Other means of stimulating reward pathways in the brain, such as drugs, sex, aggression, and intimidating others, could become relatively more attractive and less constrained by concern about violating trusting relationships. The ability to modify behavior based on negative experiences may be impaired.30

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Hard-core drug addicts, whose lives invariably began under conditions of severe stress, are all too readily triggered into a stress reaction. Not only does the stress response easily overwhelm the addict’s already-challenged capacity for rational thought when emotionally aroused, but the hormones of stress also “cross-sensitize” with addictive substances. The more one is present, the more the other is craved. Addiction is a deeply ingrained response to stress, an attempt to cope with it through self-soothing. Maladaptive in the long term, it is highly effective in the short term.

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Predictably, stress is a major cause of continued drug dependence. It increases opiate craving and use, enhances the reward efficacy of drugs, and provokes relapse to drug seeking and drug taking.31 “Exposure to stress is the most powerful and reliable experimental manipulation used to induce reinstatement of alcohol or drug use,” one team of researchers reports.32 “Stressful experiences,” another research group points out, “increase the vulnerability of the individual to either develop drug self-administration or relapse.”33 Stress also diminishes the activity of dopamine receptors in the emotional circuits of the forebrain, particularly in the nucleus accumbens, where the craving for drugs increases as dopamine function decreases.34 The research literature has identified three factors that universally lead to stress for human beings: uncertainty, lack of information, and loss of control. 35 To these we may add conflict that the organism is unable to handle and isolation from emotionally supportive relationships. Animal studies have demonstrated that isolation leads to changes in brain receptors and increased propensity for drug use in infant animals,36 and in adults isolation reduces the activity of dopamine-dependent nerve cells.37 Unlike rats reared in isolation, rats housed together in stable social groupings resisted cocaine self-administration—in the same way that Bruce Alexander’s tenants in Rat Park were impervious to the charms of heroin.38

  1. Eliot L. Gardner, “Brain-Reward Mechanisms,” chap. 5, section II, in Substance Abuse, by Lowinson et al.,

  2. M. Papp et al., “Parallel Changes in Dopamine D2 Receptor Binding in Limbic Forebrain Associated with Chronic Mild Stress-Induced Anhedonia and Its Reversal by Imipramine,” Psychopharmacology 115 (1994): 441–46.

  3. S. Levine and H. Ursin, “What Is Stress?” in Stress, Neurobiology, and Neuroendocrinology, ed. M. R. Brown, G. F. Koob, and C. Rivier (New York: Marcel Dekker, 1991), 3–21.

  4. Harold H. Gordon, “Early Environmental Stress and Biological Vulnerability to Drug Abuse,” Psychoneuroendocrinology 27 (2002): 115–26.

  5. Blanc, “Response to Stress of Mesocortico-Frontal Dopaminergic Neurons in Rats,” 265–67.

  6. S. Schenk et al., “Cocaine Self-Administration in Rats Influenced by Environmental Conditions: Implications for the Etiology of Drug Abuse,” Neuroscience Letters 81 (1987): 227–31.

  7. A. Jacobson, “Physical and Sexual Assault Histories among Psychiatric Outpatients,” American Journal of Psychiatry 146 (1989): 755–58.

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Research shows that the vast majority of physical and sexual assault victims do not spontaneously reveal their histories to their doctors or therapists.39 If anything, there is a tendency to forget or to deny pain. One study followed up on young girls who had been treated in an emergency ward for proven sexual abuse. When contacted seventeen years later as adult women, 40 percent of these abuse victims either did not recall or denied the event outright. Yet their memory was found to be intact for other incidents in their lives.40

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  1. L. M. Williams, “Recall of Childhood Trauma: A Prospective Study of Women’s Memories of Child Sexual Abuse,” Journal of Consulting and Clinical Psychology 62: 1167–76.

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