Lecture - Substance Related Disorders Etiology & Treatment.pdf

 Alcohol use disorders are not a result of any individual weakness or moral failing, but arise from a complex interaction of individual, social, cultural, and biological factors  Developmentally, alcohol use rapidly increases during adolescence, peaking in the early-mid 20s, and then gradually dec...

 Alcohol use disorders are not a result of any individual weakness or moral failing, but arise from a complex interaction of individual, social, cultural, and biological factors  Developmentally, alcohol use rapidly increases during adolescence, peaking in the early-mid 20s, and then gradually decreasing over the course of adulthood AUDs show roughly a similar pattern Need to address the developmental processes that can help explain this strong, age-graded phenomenon Processes responsible for desistence are important for understanding the population prevalence and persistence  Family, twin, and adoption studies Substance abuse has a notable genetic component  Heritability estimates range from 40-64% (no sex diffs)  Recent meta-analysis: heritability across studies = ~50% (Verhulst et al., 2015)  Applies more to AUD diagnosis rather than alcohol related traits  Concordance rates of AUD in identical twins = 50%  Among fraternal twins, closer to 30%  In studies of adopted children, risk for substance-related disorders most closely follows substance use patterns of biological parents  Twin studies suggest that environmental factors more likely to account for initiation of alcohol-related behaviors while genetic factors account for alcohol use severity  Genetic differences in alcohol metabolism Alcohol dehydrogenase (ADH) and mitochondrial form of aldehyde dehydrogenase (ALDH2) are liver enzymes ALDH2 gene has two primary alleles: ALDH2*1 and ALDH2*2  Carriers of ALDH2*2 allele have impaired alcohol metabolism  If they drink alcohol, acetaldehyde accumulates, leading to the emergence of flushing, headache, sweating, tachycardia, nausea, and vomiting (which serve to protect against AUD)  This polymorphism is carried by ~40% of East Asian individuals but is rare in European people Polymorphisms in ADH genes (eg, ADH1B*2) protect against alcohol use disorders  Largest genome-wide association meta-analysis of AUD risk found 10 different risk loci (Kranzler et al., 2019)  Once again, POLYGENIC transmission is the rule  Premise: Genetically based individual differences in alcohol effects are related to risk for developing Alcohol Use Disorders (AUDs)  Those with a family history of AUDs show less sensitivity to the effects of a given dose of alcohol  Schuckit and colleagues (Schuckit & Smith, 2001) have demonstrated that low sensitivity predicts alcohol use disorders prospectively in young adulthood.  Some of their data… BAC Subjective Intoxication Body Sway From Eng, Schuckit, & Smith, 2005  As individuals drink more alcohol over time, progressive changes occur in the structure and function of their brains  These changes can compromise brain function and drive the transition from controlled, occasional use to chronic misuse, which can be difficult to control  The changes can endure long after a person stops consuming alcohol, and can contribute to relapse in drinking - SUD’s/Addiction can be framed as a repeating cycle, with three stages - Each stage is linked to and feeds on the others and involve three domains: 1 - incentive salience (basal ganglia) 2 - negative emotional states (extended amygdala 3 - executive function (prefrontal cortex) - A person may go through this 3-stage cycle over the course of weeks or months, or progress through it several times in a day, and can enter the cycle of addiction at any of the stages- 1. Binge/Intoxication Stage – Reward, Incentive Salience, & Pathological Habits During this stage, a person experiences the rewarding effects of alcohol (e.g., euphoria), the reduction of anxiety, and the easing of social interactions, which activates reward circuits and engages “incentive salience” circuits Incentive salience circuits link the pleasurable, rewarding experience with “cues,” that is, the people, places, and things present when drinking, such that the cues themselves gain motivational significance Repeated activation of the basal ganglia’s reward system reinforces alcohol drinking behavior, increasing the likelihood of repeated consumption 2. Withdrawal/Negative Affect – Reward Deficits and Stress Surfeit When a person who is addicted to alcohol stops drinking, they experience withdrawal symptoms, including physical (sleep disturbances, pain, feelings of illness) and emotional (dysphoria, irritability, anxiety, and emotional pain) symptoms. The person feels alcohol is needed for temporary relief from discomfort and emotional pain. The negative feelings associated with alcohol withdrawal come from two sources: First, a diminished activation in the reward systems—or a reward deficit—of the basal ganglia makes it difficult for people to experience the pleasures of everyday living. Second, an increased activation of the brain’s stress systems—or a stress surfeit—in the extended amygdala contributes to anxiety, irritability, and unease At this stage, the person no longer drinks alcohol for the pleasurable effects (“high”), but rather to escape the “low” feelings to which chronic alcohol misuse has contributed. 3. Preoccupation/Anticipation Stage – Craving, Impulsivity, & Executive Function Deficits A person becomes preoccupied with alcohol and how to get more of it, and looks forward to the next time he or she will consume it The prefrontal cortex—responsible for executive function, including the ability to organize thoughts and activities, prioritize tasks, manage time, and make decisions—is compromised in people experiencing alcohol addiction. The person with an addiction has impairments in executive function processes that normally limit impulsive and compulsive responses. The person has strong urges or cravings to drink, especially in response to stress, related negative emotions, and cues that are part of the incentive salience circuits activated in the first stage of the cycle.  Exposure to drugs is prerequisite for use of drugs Media, family, peers Parents and the family appear critical  Consistent finding: more alcohol supply by parents → higher rates of adol. drinking, negative consequences, and AUD symptoms Influences how people use substances as well as how people think about substance users  Permissiveness  Expectations of reward/punishment  Additional Risk Factors: STRESS, especially within family; economic stress  Higher rates of substance problems correlated with greater experiences of stress due to racial discrimination, gender, and/or sexual minority stress (Rose et al., 2018; Slater et al., 2017)  CLINICAL PRESENTATION Among disorders w/ lowest treatment prevalence  Only 20-25% who have mod-sev AUD receive treatment  Treatment often sought very late in the disorder’s emergence Factors impacting treatment uptake  Stigma about patients with AUDs – such as?  Clinicians not well-trained in screening for AUDs/SUDs  Little formal links between medical presentation , screening, and connection to treatment providers  May explain proliferation of private, for-profit ‘rehab centers’ - WHO Alcohol Use Risk Levels   How do we get people into the green box? Bottom line: many different ways! Research using both clinical and non-treatment-seeking samples has shown that the majority of individuals who develop AUD reduce or resolve their problem over time The pathways to improvement are heterogeneous, may occur with or without participation in treatment or mutual help groups, and involve improved functioning and well-being with or without reductions in drinking (Witkiewitz et al. 2020)  Alcoholics Anonymous (AA)/12-Step Programs Largest self-help group for problem drinkers Based on “disease model” → alcoholism is a powerful disease that requires a “higher power” to control  Clients find message useful; little evidence to support this model in the scientific literature Meetings provide support, understanding, and acceptance Promotes complete abstinence within spiritual framework  Effective? Recent review says yes, for abstinence outcomes only  AA/12-step treatment were better than other treatments for (1) continuous abstinence and (2) % days abstinent, while likely producing “substantial cost-saving benefits.”  AA/12-step treatment did as well as other treatments on other outcome measures Other non-spiritual peer-support interventions:  LifeRing or SMART Recovery  Cognitive Behavioral Therapies (CBT) solid scientific evidence – Variations of CBT: Contingency-Management Therapy  Patient and family reinforce behaviors inconsistent with drinking and teach problem drinker how to deal with uncomfortable situations  E.g., avoiding places associated with drinking; refusing the offer of a drink Relapse prevention  Strategies to prevent relapse – cognitive and relaxation interventions Controlled drinking/Guided Self-Change  Premise: problem drinkers can consume alcohol in moderation  Avoid total abstinence and avoid inebriation  Motivational Enhancement Therapy (MET): Effective method of engaging people in treatment Explore client goals, reasons for wanting or not wanting to change, and evaluate pathways to achieve those goals Contrast to traditional “blame” approach - Carvalho et al., 2019; Lancet - Carvalho et al., 2019; Lancet  Important to make an informed decision and avoid the “1-size-fits-all” approach Abstinence may be valued but is not a requirement  Studies support adoption of a more flexible definition of recovery that focuses on improvements in areas of functioning adversely affected by drinking and enhanced access to non-drinking rewards  NIAAA Treatment Navigator website Basic premise: different patients with different patterns of AUD will need different treatments Guides patients, providers to evidence-based treatments that match specific client backgrounds / needs  Includes telehealth and online options - - - Effective treatments are available Focused treatments more effective than unstructured conversations MOST EFFECTIVE: motivational enhancement therapy, community reinforcement approach, guided self-change, behavior contracting, social skills training, some pharmacological interventions - Carvalho et al., 2019; Lancet - Medication-Assisted Treatment (MAT) - Using other drugs to combat opioid cravings - 87% of people with Opioid Use Disorder (OUD) do not receive evidence-based treatments - Utilization of medications for OUD, esp. buprenorphine, has risen across most states over past decade, but cannot keep pace with need/use Source: Krawczyk et al., 2022; Intl J Drug Pol.  Another option, more common in other countries (Canada, UK, Spain, Portugal, Netherlands): Prescription heroin – associated with steep drops in street heroin use  Randomized controlled trial pub’d in New England Journal of Medicine (2009): 67% reduction in use in prescription heroin group vs 47% in methadone group  Faced with a massive crisis associated with illicit drug addiction, Portugal decriminalized ALL drugs in 2001 Note that drugs weren’t ‘legalized’ and technically weren’t even decriminalized: It set up new incentives for seeking help: People caught using drugs can be sent to a special commission that tries to get them into free treatment  If drug users do not cooperate or they show serious problems, the commission can impose penalties, such as barring people from taking some jobs or visiting certain locations Large reductions in HIV and drug-related crime through mid-20teens  However, those gains are now disappearing  Police are less motivated to register people who misuse drugs  There are year-long waits for state-funded rehabilitation treatment even as the number of people seeking help has fallen  Urban visibility of the drug problem is at its worst point  State-funded nongovernmental organizations have largely taken over responding to people with addiction  And drug use may be increasing:  Percent of adults who have used illicit drugs increased to 12.8% in 2022, up from 7.8 in 2001, though still below European averages  Prevalence of high-risk opioid use higher than Germany’s, but lower than France and Italy After years of economic crisis, Portugal decentralized its drug oversight operation in 2012:  A funding drop from 76 million euros to 16 million euros forced Portugal to outsource work previously done by the state to nonprofit groups (street teams that engage with people who use drugs)  The number of users being funneled into drug treatment in Portugal has sharply fallen, going from a peak of 1,150 in 2015 to 352 in 2021  Seeing similar problems in Oregon’s decriminalization experience since 2020 There were no enforcement provisions included