Etiology of substance use

substance use/addiction its epidemiology, etiology and pathophysiology

1. ETIOLOGY OF SUBSTANCE USE DIORDERS Presented By : Dr. Karrar Husain Moderator : Dr. M. Amir Usmani

2. CONTENTS Introduction Brief history and epidemiology Biology Learning and conditioning Psychodynamic theory Environmental and other factors

3. INTRODUCTION DSM and ICD Terminology

4. In DSM 5 substance related disorder are classified in substance related and addictive disorder. Substance related disorder  substance use disorder and substance induced disorder. Substance use disorder in DSM-5 combines the DSM-IV categories of substance abuse and substance dependence into a single disorder measured on a continuum from mild to severe k/a substance use disorder. (only 2 are required). Substance induced disorder consist of withdrawal, intoxication, and other substance induced mental disorder. DSM 5

5. Substance-Use Disorder A. A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by 2 (or more) of the following, occurring within a 12-month period: 1. recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; neglect of children or household) 2. recurrent substance use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by substance use) 3. continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (e.g., arguments with spouse about consequences of intoxication, physical fights)

6. 4. tolerance, as defined by either of the following: a. a need for markedly increased amounts of the substance to achieve intoxication or desired effect b. markedly diminished effect with continued use of the same amount of the substance 5. withdrawal, as manifested by either of the following: a. the characteristic withdrawal syndrome for the substance b. the same substance is taken to relieve or avoid withdrawal symptoms 6. the substance is often taken in larger amounts or over a longer period than was intended. 7. there is a persistent desire or unsuccessful efforts to cut down or control substance use

7. 8. a great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects 9. important social, occupational, or recreational activities are given up or reduced because of substance use 10. the substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance 11. Craving or a strong desire or urge to use a specific substance.

8. Severity specifiers : Mild : 2-3 criteria Moderate : 4 or 5 Severe : 6 or more

9. ICD 10 F10 - F19 MENTAL AND BEHAVIOURAL DISORDERS DUE TO PSYCHOACTIVE SUBSTANCE USE F10.- DISORDERS DUE TO USE OF ALCOHOL F11.- DISORDERS DUE TO USE OF OPIOIDS F12.- DISORDERS DUE TO USE OF CANNABINOIDS F13.- DISORDERS DUE TO USE OF SEDATIVES OR HYPNOTICS F14.- DISORDERS DUE TO USE OF COCAINE

10. F15.- DISORDERS DUE TO USE OF OTHER STIMULANTS, INCLUDING CAFFEINE F16.- DISORDERS DUE TO USE OF HALLUCINOGENS F17.- DISORDERS DUE TO USE OF TOBACCO F18.- DISORDERS DUE TO USE OF VOLATILE SOLVENTS F19.- DISORDERS DUE TO MULTIPLE DRUG USE AND USE OF OTHER PSYCHOACTIVE SUBSTANCES

11. Dependence - The repeated use of a drug or chemical substance, with or without physical dependence. Physical dependence indicates an altered physiologic state caused by repeated administration of a drug, the cessation of which results in a specific syndrome. Abuse - Use of any drug, usually by self-administration, in a manner that deviates from approved social or medical patterns. Misuse - Similar to abuse, but usually applies to drugs prescribed by physicians that are not used properly.

12. Addiction - The repeated and increased use of a substance, the deprivation of which gives rise to symptoms of distress and an irresistible urge to use the agent again and which leads also to physical and mental deterioration. Intoxication - A reversible Syndrome caused by a specific substance that affects one or more of the following mental functions: memory, orientation, mood, judgment, and behavioral, social, or occupational functioning. CTP 9 th edition.

13. Cross-tolerance - Refers to the ability of one drug to be substituted for another, each usually producing the same physiologic and psychological effect (e.g., diazepam and barbiturates). Also known as cross-dependence. Codependence - Term used to refer to family members affected by or influencing the behavior of the substance abuser. Related to the term enabler , which is a person who facilitates the abuser’s addictive behavior. Enabling also includes the unwillingness of a family member to accept addiction as a medical-psychiatric disorder or to deny that person is abusing a substance. CTP 9 th edition.

14. HISTORY and EPIDEMIOLOGY

15. HISTORY Opium has been used for medicinal purposes for at least 3,500 years. References to cannabis (marijuana) as a medicine can be found in ancient chinese herbals. Wine is mentioned frequently in the bible. Indigenous people of the western hemisphere were smoking tobacco and chewing coca leaves generations before the arrival of the spaniards . In asia , opium smoking was a major problem in the 18th and 19th centuries, new problems related to opium were seen there and in other parts of the world after morphine, its most active alkaloid, was isolated in 1806.

16. Intravenous (IV) morphine and heroin use began to spread in the early part of the 20th century. Although tobacco use was common by the 19th century, the serious adverse medical consequences associated with it did not emerge until the 20th century, when new methods of curing the leaves produced a mild smoking tobacco, and cigarettes were introduced

17. Medicalizing Excessive Drug Use In 1810, Benjamin Rush , suggested that excessive use of alcohol was a disease. in 1835, Samuel Woodward , a pioneer in the establishment of asylums for the insane, advocated similar asylums for inebriates. In 1870, estb . Of The American Association for the Cure of Inebriates (AACI), dedicated to setting up hospitals for such people, conducting research, and teaching medical students and physicians how to treat inebriety. Thomas Crothers , the secretary of AACI, saw inebriate asylums as places to treat all those who used any variety of intoxicant or narcotic to excess CTP 9 th edition.

18. Burden of problem According to WHO there are 2 billion alcohol users, 1.3 billion smokers and 185 million drug users. http://www.who.int/substance_abuse/facts/global_burden/en/

19. There is no National epidemiological data collection system for Alcohol and Drugs in INDIA . Prevalence estimates for alcohol use disorders (12-month prevalence, %) Female (15+ years) - Year 2004 -0.42 Male (15+ years) - Year 2004 -3.47 Prevalence estimates for drug use disorders (12-month prevalence, %) Female (15+ years) - Year 2004- 0.03 Male (15+ years) - Year 2004 - 0.24 World Health Organization 2010 Global Burden of Disease (GBD) estimate, 2004.

20. Risk factors Men > women, 2:1 Adults who did not complete high school are more likely than college graduates to have become dependent on illegal drugs. Unemployed : employed.. 2: 1 Younger age of onset. Individuals with a serious mental illness are more than twice as likely to have used an illegal drug and to have been cigarette smokers. CTP 9 th ed

21. BIOLOGY 1- ACUTE EFFECT OF DRUGS ( REWARD CIRCUITS) 2-MECHANISM OF ACTION OF VARIOUS DRUGS 3- CHRONIC EFFECTS OF DRUG 4- VULNERABILITY AND GENETICS

22. Substance abuse and addiction are complex phenomena that defy simple explanation or description. A tangled interaction of factors contributes to an individual’s seeking out, using, and perhaps subsequently abusing drugs. Since more individuals experiment with drugs than eventually develop substance abuse problems, great interest persists in understanding what differentiates these groups. Factors that can play a role in drug abuse susceptibility include a person psychological makeup, biological response to drugs and environmental situation, and the availability of drugs.

23. Two biological factors contribute to substance abuse and addiction: The effects drugs of abuse exert on the individual. The biological status of the individual taking drugs .

24. DRUG ACTION Acute Actions What separates drugs of abuse from other psychoactive drugs ? One of the most striking features of drug addiction is how few chemicals are subject to abuse. All known congeners of all known chemicals, approximately 30,000,000 chemical substances [Gardner, 2005]. Yet, only approx 100 are addictive. What makes these 100 chemicals addictive, while the remaining 30,000,000 chemicals lack this property?

25. All addictive drugs are subjectively rewarding, reinforcing and pleasurable. All addictive drugs ( excep ) activate reward circuitry of brain -producing subjective ‘high’ that drug abuser seeks. Degree of such activation of the brain’s reward circuitry correlates well with the degree of subjective high.

26. REWARD CIRCUITS Stahl’s essential psychopharmacology.

27. The mesolimbic dopamine circuit The final common pathway of reinforcement and reward. Also k/a “pleasure center” of the brain and dopamine to be the “pleasure neurotransmitter. Natural ways to trigger your mesolimbic dopamine neurons to release dopamine, ranging from intellectual accomplishments, to athletic accomplishments, to enjoying a good symphony, to experiencing an orgasm. These are called as “natural highs”. The inputs to the mesolimbic pathway that mediate these natural highs include a naturally occurring substances - endorphins, anandamide , acetylcholine, and dopamine itself.

28. Drugs of abuse also have a final common pathway of causing the mesolimbic pathway to release dopamine, more explosive and pleasurable than that which occurs naturally. A drug-induced reward causes such wonderful feeding of dopamine to postsynaptic limbic dopamine receptors that they furiously crave even more drug to replenish dopamine once the drug stops working, leading one to be preoccupied with finding drug and thus beginning a vicious cycle of abuse, addiction, dependence, and withdrawal

29. 50 100 150 200 60 120 180 Time (min) % of Basal DA Output NAc shell Empty Box Feeding Source: Di Chiara et al. FOOD 100 150 200 DA Concentration (% Baseline) Mounts Intromissions Ejaculations 15 5 10 Copulation Frequency Sample Number 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Scr Scr Bas Female 1 Present Scr Female 2 Present Scr Source: Fiorino and Phillips SEX Natural Rewards Elevate Dopamine Levels

30. 100 200 300 400 500 600 700 800 900 1000 1100 1 2 3 4 5 hr Time After Amphetamine % of Basal Release DA DOPAC HVA Accumbens AMPHETAMINE 100 200 300 400 1 2 3 4 5 hr Time After Cocaine % of Basal Release DA DOPAC HVA Accumbens COCAINE 100 150 200 250 1 2 3 hr Time After Nicotine % of Basal Release Accumbens Caudate NICOTINE Source: Di Chiara and Imperato Effects of Drugs on Dopamine Release 100 150 200 250 1 2 3 4hr Time After Ethanol % of Basal Release 0.25 0.5 1 2.5 Accumbens Dose (g/kg ip) ETHANOL Much greater Activity than any Other drug of abuse.

31. The reactive reward system Addicts act impulsively, automatically, and obligatorily to cues that lead them to seek and ingest more drug..mediated by reactive reward system. Upon repeated exposure to drugs of abuse, this reactive reward system pathologically “learns” to trigger drug seeking behavior and “remembers” how to do this when confronted with internal cues such as craving and withdrawal and external cues from the environment such as people, places, and paraphernalia associated with past drug use.

32. Connections of VTA DA neurons with the amygdala are involved with reward learning. Once reward learning has been conditioned in the amygdala , connections of the amygdala back to the VTA DA neuron later communicate whether anything relevant to the previously rewarding drug abuse experience is being detected.

33. Connections of the amygdala with the nucleus accumbens tell the spiny neurons there that emotional memories have been triggered by internal or external cues, and instruct these spiny neurons to take action impulsively, right away, automatically, obligatorily, and without thought, almost as a reflex action, to find and take more drugs.

34. The reflective reward system Includes important connections from prefrontal cortex down to the nucleus. These connections are the first legs of cortico - striatal -thalamic-cortical (CSTC) loops. Prefrontal projections from the orbitofrontal cortex may be involved in regulating impulses, Dorsolateral prefrontal cortex (DLPFC)  analyzing the situation, and regulating whether it is rational to take an action. Ventromedial prefrontal cortex may try to integrat impulsiveness from OFC with analysis and cognitive flexibility from DLPFC with its own regulation of emotions, and come up with a final decision of what to do.

35. The reflective reward system is also involved in the will power to resist drugs. When fully developed and functioning properly ..it provide motivation for pursuing more naturally rewarding experiences such as education, accomplishments, recognition, financial benefits, career development, enriching social and family connections, etc

36. Turning reward into goal-directed behavior: output of the reward system The output of the reward system is really just the completion of CSTC loops starting in the prefrontal cortex. Nucleus Accumbens  via GABA- ergic neurons to the ventral pallidum  via GABA- ergic neurons to the thalamus, and then project back up to the prefrontal cortex, where behaviors are implemented, such as learning and activities resulting in long-term rewards or drug-seeking behavior resulting in short-term rewards.

37. First time you take a drug, there is immediate pharmacological action upon the mesolimbic pleasure center……Dopamine is released, pleasure is experienced and the amygdala “learns” that this is a rewarding experience. Reward has now been conditioned in the amygdala .

38. when cues are encountered, the amygdala signals dopamine neurons in the ventral tegmental area (VTA) that something good is coming ,This leads to dopamine release in the nucleus accumbens which triggers GABA- ergic input to the thalamus, thalamic input to the prefrontal cortex, and leads to action such as drug-seeking behavior

39. But can impulses from the reactive reward system ever be resisted? What is the role of will power over temptation? when temptation occurs with the opportunity to ingest drugs arising at a party, in a bar, or when seeing or feeling drugs or their paraphernalia, the amygdala anticipates the pleasure that the drugs would bring in by signaling an impulsive choice to the VTA that urges output from the nucleus accumbens to engage in behavior that leads to ingesting the drugs again. The OFC in prefrontal cortex is signaling craving and voting for more drug ingestion as well.

40. When drug anticipation occurs, this signals an impulsive choice to the ventral tegmental area (VTA) to release dopamine in the nucleus accumbens , which in turn produces output to engage in behavior that leads to ingesting drugs again .

41. Will power can be represented in the reward system as the ability of prefrontal circuits to become activated and prevent impulses being expressed as drug-seeking behavior. For example, Reflective reward system allows the time to evaluate whether losing your driver’s license, getting into an auto accident, losing your job or your relationship is worth becoming intoxicated, and if the answer is no, can trigger the choice not ingesting the drug.

42. The dorsolateral prefrontal cortex (DLPFC) interprets the various signals and, showing cognitive flexibility, decides whether to take the action of drug ingestion (5). ( B) If the reflective reward system (prefrontal circuits) is activated , this can prevent impulses (temptation) from being expressed as behavior.

43. MECHANISM OF ACTION OF VARIOUS DRUGS

44. Nicotine Nicotine directly causes dopamine release in the nucleus accumbens by binding to alpha 4 beta 2 nicotinic postsynaptic receptors on dopamine neurons in the ventral tegmental area (VTA). Nicotine binds to alpha 7 nicotinic presynaptic receptors on glutamate neurons in the VTA, which in turn leads to dopamine release in the nucleus accumbens . Nicotine also seems to desensitize alpha 4 beta 2 postsynaptic receptors on GABA interneurons in the VTA; the reduction of GABA neurotransmission disinhibits mesolimbic dopamine neurons and thus is a third mechanism for enhancing dopamine release in the nucleus accumbens .

45. Alcohol The pharmacology of alcohol is poorly understood and its mechanism of action is thought to be somewhat nonspecific. Alcohol can have effects on a wide variety of neurotransmitter systems. Enhancing inhibitory neurotransmission at GABA synapses and reducing excitatory neurotransmission at glutamate synapses  depress CNS neuronal functioning  intoxicating, amnestic , and ataxic effects. Alcohol either act directly mu opiate receptors or indirectly act by releasing endogenous opiates such as enkephalin …actions on opiate synapses is thought to be the release of DA in the nucleus accumbens . Alcohol may also have some actions on cannabinoid receptors.

46. Opiates Act as agonists at mu, delta, and kappa opiate receptors, particularly at mu sites. Opiates act as neurotransmitters released from neurons that arise in the arcuate nucleus and project both to the VTA and to the nucleus accumbens and release enkephalin . The opiates induce euphoria, which is their main reinforcing property.

47. Stimulants The main mechanism of action of cocaine is to block reuptake and cause the release of monoamines, principally dopamine (DA) but also norepinephrine (NE) and serotonin (5HT). Amphetamine as an inhibitor of the dopamine transporter (DAT) and also of the vesicular monoamine transporter (VMAT). The potential abuse properties of stimulants stem from their ability to enhance dopamine release in the nucleus accumbens .

48. Marijuana delivers its active ingredients, the cannabinoids (e.g., THC; delta-9-tetrahydrocannabinol), which interact with the brain’s own cannabinoid receptors to trigger dopamine release in the nucleus accumbens . Sedative/ hypnotics are positive allosteric modulators (PAMs) for GABA-A receptors.

49. Inhalants : Agents such as toluene are thought to be direct releasers of dopamine in the nucleus accumbens . Phencyclidine and ketamine : act as antagonists of NMDA receptors, actions at glutamate synapses within the reward system. Hallucinogens : The hallucinogens are a group of agents that act at serotonin synapses in the reward system.

50. Addictive drugs of different classes act on this brain reward neural circuit at different points to activate the circuit and produce drug- induced high. Barbiturates, benzodiazepines, cannabinoids, ethanol, nicotine and opiates act on synapses in ventral tegmental area. Amphetamines, cannabinoids, cocaine, opiates and dissociative anesthetics eg . ketamine and phencyclidine act on synapses in nucleus accumbens Addictive drugs effectively ‘hijack’ brain’s reward circuits, activating them more strongly than natural rewards, and diverting the drug addict’s life to pursuit of drug- induced pleasure at the expense of ‘getting off’ on life’s normal pleasures and rewards….to begin with anyway!

51. CHRONIC EFFECTS OF DRUG

52. NEUROADAPTATIONS IN SUBSTANCE DEPENDENCE Chronic drug and alcohol use produces numerous neurobiological changes in several brain regions. These changes occur at virtually every level of information processing, ranging from neurotransmitters and receptors to intracellular signaling pathways and regulation of gene expression to long-term structural changes that alter synaptic plasticity. These changes ultimately could alter entire neural networks with impact on motivation, emotion, decision making, and other cognitive processes.

53. From: Nestler - Transcriptional and Epigenetic Mechanisms of Addiction http://az9194.vo.msecnd.net/pdfs/100401/EB10L5.pdf

54. From: Nestler - Transcriptional and Epigenetic Mechanisms of Addiction http://az9194.vo.msecnd.net/pdfs/100401/EB10L5.pdf

55. From: Nestler - Transcriptional and Epigenetic Mechanisms of Addiction http://az9194.vo.msecnd.net/pdfs/100401/EB10L5.pdf

56. VULNERABILITY AND GENETICS

57. why does one person become dependent on drugs while another, exposed to the same environment and experiences, does not? There is likely to be a genetic component to substance abuse and addiction. That is, inherited differences among individuals affect their response to drugs.

58. The children of alcoholic parents are at higher risk for developing alcoholism and drug dependence than are children of nonalcoholic parents. The higher risk for alcoholism manifests itself even when children are adopted by nonalcoholic families soon after birth. Dependence on other drugs also shows a familial pattern. Numerous studies of laboratory animals have revealed genetically transmitted differences in the reinforcing effects of alcohol and various drugs, such as cocaine and opioids , and show that genetic factors powerfully influence sensitivity to toxic effects.

59. Studies of boys adopted soon after birth have shown higher rates of alcoholism among those whose biological fathers were alcoholics than among those whose biological fathers were not. Some adoption studies point toward subtypes of alcoholism among men: One is a later-onset disorder that is less severe and far more sensitive to environmental factors (type I OR low risk), and the other is associated with early-onset, antisocial behavior and criminality in the biological fathers and a stronger genetic basis for the increased vulnerability (type II OR high risk).

60. High risk and low risk children and adolescents HR children have : smaller (slower maturing) brain areas - Frontal BRAKES - ANT CING Less mature connecting WHITE matter tracts - reduced white matter being associated with greater impulsivity. ALTERED EMOTIONAL REACTIVITY AND REACTION TO SOCIAL CUES. Deficits in recognizing anger and fear recognition  difficulties in recognizing and responding appropriately to others emotions and thoughts------ >> More asocial and drinking helps them to become more prosocial which is highly rewarding.

61. Hypo-activation in high risk subjects for Recognition of Angry & Fearful faces  inability to recognize these emotions may lead to increased risk taking behavior. HR respond differently to alcohol Greater CNS “stimulation”….greater reinforcing effect of alcohol; BUT…… HR receive less warning of intoxication . HR young adults receive increased CNS reinforcement from alcohol …but lower negative signals of intoxication  frequent drug use and bingeing.

62. P300 A P300 event-related potential (ERP) is a brief electrical wave in the EEG, reflects active stimulus processing that is affected by attention and memory and is genetically mediated Measure of the way the brain pays attention and discriminates between potentially important and non-important stimuli. Marker of CNS hyperexcitability - lower amplitude of P300 associated with generalized disinhibition , associated with the early onset of a number of deviant behaviors Several studies: HR children have demonstrated reduced P300 amplitude Differences not always replicable in adults (Gandhi & Benegal , 2004) Benegal V, Jain S, Subbakrishna DK, Channabasavanna SM.   Psychiatr Genet. 1995;5(4):49-56. Iacono and McGue , 2006; Porjesz and Rangaswamy , 2007

63. ‘ Reward Deficiency’ as a Driving Force in Addiction In 1996, Blum et al. proposed that many aspects of addiction are driven by a chronic basal deficiency in brain reward. The fundamental notion : that drug addicts are either born with or acquire a deficiency state in the dopaminergic brain substrates of reward and turn to addictive drug use to remedy this reward deficiency. ‘IF this be so, then our goals are really two- fold: first, to rescue addicts from the clutches of their addictions, and second, to restore their reward systems to a level of functionality that will enable them to function appropriately. Gardner (2011) In, Clark MR, Treisman GJ ( eds ): Chronic Pain and Addiction. Adv Psychosom Med. Basel, Karger , 2011, vol 30, pp 22–60

64. Genetics Heritability estimates for nicotine, alcohol, and drug addiction are in the range of 50% to 60%. In general, it appears that environmental factors have a stronger effect on initiation, whereas genetic factors play a larger role in the transition from regular use to the development of addiction. (Heath et al., 1997;Tsuang et al., 1998;Kendler et al., 2003;Li, 2006) ( Vink et al., 2005). The Genetic Basis of Addiction, Chad Epps and Elizabeth Laura Wright

65. Genetics of Alcohol Dependence Polymorphisms in the alcohol metabolizing enzymes are the most strongly associated genetic variants that influence alcohol consumption and alcohol dependence. Protective role for the deficiency of ALDH2 in alcohol dependence Several known genetic variants cause amino acid changes in these proteins and alter enzymatic activity. ADH1B*2, or rs1229984, diminishes ADH1b enzymatic activity several fold, and ALDH2*2, or rs671, results in a nearly inactive enzyme ( Edenberg , 2007). These genetic variants reduce the probability of heavy alcohol consumption and the development of alcohol dependence.

66. The mechanism by which variants of these enzymes influence the risk of developing alcohol dependence is hypothesized to be through an elevation of acetaldehyde levels after drinking, leading to facial flushing, nausea, and other adverse reactions. (Enoch, 2008

67. Genetic influences for other Drug Addictions Endogeneous opioid system clearly plays a role in addiction, and an amino acid change in the μ opioid receptor (OPRM1) displays functional changes with up to threefold variation in the affinity of the receptor to bind beta-endorphin. However, a large scale meta-analysis does not demonstrate that this variant alters the risk of developing addiction. (Bond et al., 1998). (Arias et al., 2006).

68. Studies of Nicotine Dependence The most robust genetic finding that alters the risk of developing heavy smoking is in the chromosome 15q25 region, which contains the α5, α3, and β4 nicotinic receptor subunit gene cluster ( CHRNA5, CHRNA3, CHRNB4). Variation in an independent group of nicotinic receptors is also associated with the development of heavy smoking and nicotine dependence. The nicotinic receptor gene cluster on chromosome 8 that includes the α6 and β3 nicotinic receptor subunit gene cluster ( CHRNA6, CHRNB3) is correlated with smoking behavior.

69. The importance of nicotine metabolism and variation in the CYP2a6 region on chromosome 19 was recently reinforced by the GWAS meta-analysis studies in which variants in this region were associated with number of cigarettes smoked per day. ( Thorgeirsson et al., 2010; Tobacco and Genetics Consortium, 2010).

70. The chromosome 15 variant in the α5 nicotinic receptor, which influences the development of nicotine dependence, has also been independently shown to contribute to the occurrence of alcohol and cocaine dependence. The minor allele is correlated with an increased risk for nicotine dependence is associated with a decreased risk for alcohol and cocaine dependence. (Grucza et al., 2008; Chen et al., 2009; Sherva et al., 2010)

71. Learning and Conditioning

72. Drug use, whether occasional or compulsive, can be viewed as behavior maintained by its consequences. Any event that strengthens an antecedent behavior pattern can be considered a reinforcer of that behavior. In that sense, certain drugs reinforce drug-taking behavior. Drugs can also reinforce antecedent behaviors by terminating some noxious or aversive state such as pain, anxiety, or depression. In some social situations, the use of the drug can be reinforcing if it results in special status or the approval of friends.

73. Each use of the drug evokes rapid positive reinforcement, either as a result of the rush (the drug-induced euphoria), alleviation of disturbed affects, alleviation of withdrawal symptoms, or any combination of these effects. The paraphernalia (needles, bottles, cigarette packs) and behaviors associated with substance use can become secondary reinforcers , as well as cues signaling availability of the substance, and in their presence, craving or a desire to experience the effects increases.

74. With socially acceptable substances, such as tobacco, use becomes so woven into the matrix of daily functioning that some users are reminded of the substances when performing ordinary tasks.

75. Classical Conditioning Opioid and alcohol withdrawal phenomena can be conditioned to environmental or interoceptive stimuli. For a long time after withdrawal (from opioids , nicotine, or alcohol), the addict exposed to environmental stimuli previously linked with substance use or withdrawal may experience conditioned withdrawal, conditioned craving, or both. The most intense craving is elicited by conditions associated with the availability or use of the substance, such as watching someone else use heroin or light a cigarette or being offered some drug by a friend. Cues induce memories of drug-induced euphoria are more important for stimulating craving and in predisposing to relapse.

76. Withdrawal Syndromes and Negative Reinforcement Aversive withdrawal phenomena and negative reinforcement is equally important, or even dominant in substance use. Eg …in people who become dependent on benzodiazepines in the course of treatment for anxiety syndromes, when drug use is interrupted, some seem to experience a reappearance of the original symptoms, whereas others have new distressing symptoms indicating withdrawal. The use of benzodiazepines alleviates both kinds of aversive states. The alcoholic, the heavy smoker, and the heroin user may experience, simultaneously or sequentially, relief of withdrawal, a sense of ease, and perhaps alleviation of dysphoria and depression after taking substance.

77. PSYCHODYNAMIC FACTORS

78. According to classic theories, substance abuse is : A masturbatory equivalent(some heroin users describe the initial “rush” as similar to a prolonged sexual orgasm), A defense against anxious impulses, or a manifestation of oral regression (i.e., dependency). Recent psychodynamic formulations relate substance use as a reflection of disturbed ego functions (i.e., the inability to deal with reality).

79. As a form of self-medication, alcohol may be used to control panic, opioids to diminish anger, an amphetamines to alleviate depression. Some addicts have great difficulty recognizing their inner emotional states, a condition called alexithymia (i.e., being unable to find words to describe their feelings).

80. ENVIRONMENTAL AND OTHER FACTORS

81. Stress, drug use and addiction Stress activates the same brain [reward] systems responsible for the positive reinforcing effect of drugs It increases physiological sensitivity to drugs It increases desire to improve mood with drugs after exposure to stress. Stress more strongly predicts drug use when there is a psychiatric disorder, poor parenting, family dysfunction, and adverse neighborhood characteristics. Stress, lack of social supports, and poor coping skills predict early onset and escalation of drug use, relapse, and treatment resistance.

82. Interestingly , Post-Traumatic Stress Disorder (PTSD) often precedes drug use in girls, but occurs more often after drug use in boys. Girls are at increased risk for substance abuse when exposed to the stressors of family violence and alcoholism. Preventive Implications : Sex differences should be taken into account in identifying factors that contribute to drug use and in the development of a prevention or treatment plan.

83. Children exposed to stress and conflict in the home are more likely to Manifest high levels of aggressive behavior, the strongest predictor of later drug use and other risk behaviors Girls are influenced by peers differently than boys: More likely to use drugs if friends & partners are using or introduces drugs to them. Concerns about peer approval, depression and body image – all interrelated – increase susceptibility to drug use in girls.

84. Mental Health Problems Mental Health Disorders are strongly linked to drug use and dependence. Internalizing Disorders (PTSD, Depression, Anxiety disorders, Bipolar disorder) Brain responses are heightened in response to drugs. Tendency to self-medicate the anxiety & depression this process causes drug use.

85. Mental Health Problems Externalizing Disorders (Conduct Disorder, Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, Antisocial Personality Disorder) Low level of arousal in these disorders is related to an insensitivity to consequences and a need for more stimulation. Heightens risk for continued drug use to relieve symptoms. Tend to be resistant to substance abuse treatment.

86. Personality & Temperament A difficult temperament and certain personality characteristics are consistently related to heightened risk for drug use. Impulsivity Aggressiveness Sensation or novelty-seeking Negative affect Impaired judgment High activity level Risk taking tendencies Lack of regard for negative consequences Lack of pain avoidance responses Abnormal levels of arousal in response to stress.

87. Normal adolescence is characterized by greater reward anticipation, sensitivity, and sensation seeking—particularly social rewards (e.g., peer regard, gains in social status). It follows that adolescence is the period during which drug use onset is most common. And, therefore, that adolescents with especially high levels of any combination of these traits are at heightened risk. Preventive Implications : These traits can be redirected through psychosocial means to decrease risk for drug use. Prevention programs must be designed to specifically redirect this developmental track.

88. Social Cohesion = attachment to and satisfaction with the neighborhood Involves trust and support for one another in a community Maintains norms for positive social behavior Associated with lower drug use and lower drug-related mortality Discrimination and social exclusion have profound negative effects : Physical and mental health disorders, including drug use and dependence.

89. Substantial evidence indicates that changes in price and availability can alter the consumption of alcohol and tobacco. Increase in sales outlets or an extension of sales hours increases the availability of alcohol, consumption tends to increase. When the cost of either alcohol or tobacco is increased in relation to disposable income ( e.g.,by increased taxes), consumption decreases.

90. Availability and Health Professionals. physicians, dentists, and nurses have far higher rates of dependence on DEA-controlled substances, such as opioids , stimulants, and seda-tives , than other professionals of comparable educational achievement.

91. Thank you

92. Stahl’s essential psychopharmacology. CTP 9 th edition. DSM 5 ICD 10 Kaplan and sadock synopsis of psychiatry 10 th ed. The Genetic Basis of Addiction Chad Epps and Elizabeth Laura Wright,