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Chapter 17

Chap 17-Theories of Substance Use.doc

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University of Toronto Mississauga
Ayesha Khan

Theories of Substance Use, Abuse and Dependence • The brain appears to have its own “pleasure pathway,” which affects our experience of reward • This pathway begins in the midbrain ventral tegmental area and then goes forward through the nucleus accumbens and on to the frontal cortex • This pathway is rich in neurons sensitive to the neurotransmitter dopamine. • Some drugs, such as amphetamines and cocaine, act directly to increase the availability of dopamine in this pathway, leading to the strong sense of reward or “high” that these drugs produce • Other drugs increase the availability of dopamine in more indirect ways • The neurons in the ventral tegmental area are kept from continuous firing by GABA neurons, so the firing of GABA neurons reduces the “high” caused by activity in the dopamine neurons • The opiate drugs inhibit GABA, which in turn stops the GABA neurons from inhibiting dopamine, which makes dopamine available in the reward centre • The chronic use of psychoactive substances may produce permanent changes in the reward centres, causing a craving for these substances even after withdrawal symptoms pass. • The repeated use of such substances as cocaine, heroin, and amphetamines causes dopamine neurons to become hyperactive or sensitized • This sensitization can be permanent, so that these neurons will be activated more highly by subsequent exposure to the psychoactive substance or by stimuli that are associated with the substance (such as the pipe that a cocaine user formerly used to smoke crack) • This sensitization creates a chronic, strong craving for the substance, which is made worse every time a former user comes into contact with stimuli that remind him or her of the substance • This craving can create a powerful physiological motivation for relapsing back into substance abuse and dependence • Substances that have especially rapid and powerful effects on the brain but also wear off very quickly, such as cocaine, create great risk for dependency • Psychoactive drugs affect a number of other biochemical and brain systems. • Alcohol has its sedative and antianxiety effects largely by enhancing the activity of the neurotransmitter GABA in the septal-hippocampal system • Alcohol also affects serotonin systems, which in turn are associated with changes in mood • Alcoholics and other drug addicts were simply perceived as weak, bad people who would not exert control over their impulses. • The disease model of alcoholism and other drug addictions views these disorders as incurable physical diseases, like epilepsy or diabetes Biological Theories: • People who become substance dependent or abusive may react differently physiologically to substances than do those who do not become dependent or abusive • Alcoholism, and perhaps other forms of substance dependence, really represents an underlying biological depression Genetic Factors • Family history, adoption, and twin studies conducted in Canada and the United States all suggest that genetics may play a substantial role in determining who is at risk for substance use disorders • Family studies show that the relatives of people with substance-related disorders are eight times as likely to also have a substance disorder as are the relatives of people with no substance-related disorder • There seems to be a common underlying genetic vulnerability to substance abuse and dependence in general, perhaps accounting for the fact that individuals who use one substance are likely to use multiple substances. • Twin studies have clearly shown that a substantial portion of the family transmission of substance abuse and dependence is due to genetics • Some studies suggest that genetics play a stronger role in alcohol use disorders among men than women • Some twin studies find no evidence for a genetic contribution to alcohol dependence in women, or they find that the genetic contribution for women is less than that for men • Genetic effects were found only in males, while in females substance use problems were entirely caused by environmental factors • One large twin study found similar heritability for alcohol dependence in women and men, whereas another study found modestly higher heritability for women than for men • Environmental circumstances, such as sexual abuse, are stronger predictors of alcoholism in women than in men, however • The first reports suggesting that genes play a role in smoking were published half a century ago by Fisher (1958), who found that the concordance rate for smoking is significantly higher in monozygotic twins than in dizygotic twins • The genes that confer vulnerability to the initiation of smoking are distinct from the genes that pertain to the persistence of smoking • There is less than 40% overlap in the genes implicated in smoking persistence versus smoking initiation • Genes affect vulnerability to substance use disorders in part by influencing the functioning of neuro transmitter systems involved in the metabolism and biosynthesis of substances • A variation in two genes (called ADH2 and ADH3) that control the enzymes that break down alcohol into its metabolite, acetaldehyde, is related to low alcohol risk in Asian populations • A variation in one of the genes for aldehyde dehydrogenase, the enzyme that breaks down acetaldehyde, the toxic metabolite of alcohol, into acetic acid, is associated with a very low risk for alcoholism in Asians • Persons with this genetic variant experience a buildup of acetaldehyde when they drink alcohol, leading to an aversive flushing response, which usually discourages alcohol use. • Other genes involved in drug abuse are related to central nervous system functioning, including genes associated with the GABA- benzodiazepine receptor complex, the NMDA receptor (a glutamate receptor that is sensitive to alcohol), calcium channels, cyclic AMP, and G proteins • Much research has focused on the genes controlling the dopamine system, given its importance in the reinforcing properties of substances. • Genetic variation in the dopamine receptor gene (called DRD2) and the dopamine transporter gene (called SLC6A3) may influence dopamine concentrations at the synapses and responses to dopamine, thereby influencing how reinforcing a person finds such substances as nicotine • The rewards of addictive drugs are habit forming because they act on brain circuits that naturally regulate biological rewards • People who have certain abnormalities in these genes that result in more dopamine at the synapses appear less likely to become smokers than people without these abnormalities Alcohol Reactivity • When given moderate doses of alcohol, the sons of alcoholics, who are presumably at increased risk for alcoholism, experience less impairment, subjectively, in their cognitive and motor performance and on some physiological indicators than do the sons of non-alcoholics • At high doses of alcohol, however, the sons of alcoholics are just as intoxicated, by both subjective and objective measures, as are the sons of non-alcoholics • This lower reactivity to moderate doses of alcohol among the sons of alcoholics may lead them to drink substantially more before they begin to feel drunk • They may also develop a high physiological tolerance for alcohol, which leads them to ingest more and more alcohol to achieve any level of subjective intoxication • Long-term studies of men with low reactivity to moderate doses of alcohol show that they are significantly more likely to become alcoholics over time than are men with greater reactivity to moderate doses of alcohol • The low-reactivity men are especially likely to develop alcohol problems if they encounter significant stress or if they have a tendency toward poor behavioural control • Some evidence shows that low reactivity is genetically transmitted • Women may be less prone than men to alcoholism because they are much more sensitive than men to the intoxicating effects of alcohol • At a given dose of alcohol, about 30% more of the alcohol enters a woman's bloodstream than enters a man's, because women have less of an enzyme that neutralizes and breaks down alcohol • A woman experiences the subjective and overt symptoms of alcohol intoxication at lower doses than a man and may experience more severe withdrawal symptoms if she drinks too much • Women who do abuse alcohol, however, may be at more risk for the negative health effects of alcohol than are men, because their blood concentrations of alcohol are higher than those of men who abuse Alcoholism as a Form of Depression • As many as 70% of people with alcohol dependency have depressive symptoms severe enough to interfere with daily living • Early family history studies suggested that al
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