2_Harmful Substance Use.pdf

Harmful Substance Use Focus on Alcohol Use Disorder Substance use has a long history • Humans have used plants, animals, mechanical processes, and chemistry to alter mood and cognition throughout history • ~13,000 years ago: betel nut chewed for nicotine effects in Timor • ~10,000 years ago: opium...

Harmful Substance Use Focus on Alcohol Use Disorder Substance use has a long history • Humans have used plants, animals, mechanical processes, and chemistry to alter mood and cognition throughout history • ~13,000 years ago: betel nut chewed for nicotine effects in Timor • ~10,000 years ago: opium available in Europe • ~8,000 years ago: coca leaves chewed for cocaine in Peru • The legality and social acceptability of particular uses of specific substances has varied over time and between cultures There’s a lot of substance use in US Substance use rates vary, e.g., as a function of age, gender, ethnicity, country, etc. Clinical Description & Epidemiology “Alcohol ruined me financially and morally, broke my heart and the hearts of too many others. Even though it did this to me and it almost killed me and I haven't touched a drop of it in seventeen years, sometimes I wonder if I could get away with drinking some now.” – Craig Ferguson “I have absolutely no pleasure in the stimulants in which I sometimes so madly indulge. It has not been in the pursuit of pleasure that I have periled life and reputation and reason. It has been the desperate attempt to escape from torturing memories, from a sense of insupportable loneliness and a dread of some strange impending doom.” – Edgar Allen Poe Substances Listed in the DSM-5 • Alcohol • Caffeine • Sedatives, hypnotics, or anxiolytics (e.g., benzodiazepines) • Cannabis • Stimulants (e.g., cocaine) • Phencyclidine (AKA PCP) • Other Hallucinogens • Inhalants • Opioids (e.g., Fentanyl) • Tobacco • All of these substances are “psychoactive” – that is, they can cross the blood-brain barrier and affect the functioning of the (central) nervous system • Many of these are chemical analogues of endogenous neurotransmitters (e.g., anandamide is an endogenous cannabinoid) Plus, one non-substance • Other potential behavioral addictions remain controversial among researchers (e.g., sex addiction, video game addiction, etc.) Key Terms • Craving = forceful desire or urge to use • Tolerance = increased amounts needed to achieve same effects • Associated with repeated administration • Biochemical changes over time affecting neuronal sensitivity, metabolism • The body generally wants to maintain homeostasis (“paradoxical” compensatory response; Siegel, 2005) • Withdrawal = symptoms associated with cessation of use • Substances vary in likelihood of inducing tolerance, withdrawal • Withdrawal from some drugs can be medically dangerous DSM-5 Combined Problematic Use and Dependence • DSM-IV distinguished between two categories: substance abuse disorder and substance dependence disorder, where the latter involved signs of “chemical dependence” (tolerance, withdrawal) and was considered more severe • In DSM-5, having any 2+ symptoms results in diagnosis of substance use disorder, with severity specified based on total # of criteria met • Note that the focus of the criteria is not on absolute amount or frequency of use, but on difficulty moderating use, persistent use despite negative consequences, and chemical dependence • In a really important study (N > 20K), majority of variability in alcohol-related consequences not explained by frequency/quantity of alcohol use (Prince et al., 2018) Epidemiology • Lower severity cases, esp. among young adults, will often remit w/o treatment • But SUDs can persist for many years • Variety of presentations (e.g., binging vs. daily use) Consequences • Chronic, heavy alcohol use associated with: • Increased morbidity and mortality – on average, lives of those with severe AUD ~12 years shorter than those without • Declining cognitive functioning • Frequent cause of divorce (e.g., Perreira & Sloan, 2001) • Cigarette smoking responsible for > 480,000 deaths/year in US, including nearly 30% of all cancers deaths Risk Factors & Etiological Models From liking to wanting to needing Genetic Factors Across SUDs • In families with (N = 6251) and without (N = 4083) AUD who were followed for 40+ years, almost 1/3 of those with AUD had at least one parent with problematic drinking (Cotton, 1979) • Adoption studies also consistent with heritability • But, most children who have parents w/ alcohol-related problems don’t develop SUDs • Heritability estimates are higher when people are in environments with fewer constraints on their behavior (see Harden, 2021) • Most genetic and shared environmental risk factors for SUDs don’t seem to be substance-specific • Risk structure overlaps with other psychopathologies (Kendler et al., 2003) • Some evidence that ability to tolerate large quantities, pleasurability of substances may be heritable diatheses Neurobiological Factors • Nearly all addictive drugs, including alcohol, stimulate dopamine-mediated brain systems, particularly the mesolimbic “reward pathway” • Precise mechanism of action varies • Cocaine: increases dopamine release and blocks dopamine reuptake in the VTA • Alcohol: Reduces activity of neurons that inhibit dopamine activity • Expectation of pleasure, reward; motivates approach toward use • Dopamine modulated networks in the striatum interact with the prefrontal cortex • “Reward deficiency syndrome”? (Blum) • Some evidence that people with SUDs more likely to have diminished function of D2 dopamine receptor • Cause and effect?: vulnerability model vs. toxic effect model • Does functioning of this dopaminergic system set the stage for SUDs, or does chronic substance use lead to changes in the dopamine system? Incentive Sensitization Theory • Liking (pleasure) vs. wanting (craving) • Tied to different subregions of NAc • Dopamine system becomes sensitive not only to the drug but also cues associated with the drug (e.g., needles, bars) • Sensitivity to cues induces and strengthens wanting • Compensatory response (Siegel et al., 1982) • “Captures” the motivational system: directs attention, cognition, approach • But dopamine is not the whole story (e.g., Nutt et al., 2015) • Endogenous opioid system seems to play a bigger role in liking (Smith & Berridge, 2007) • The value of a given reward depends in part on the availability of alternative rewards PFC Involvement • Self-control and behavioral monitoring: impulsive, risky behaviors; impaired self-monitoring • Motivation: high motivation to procure substances; low motivation for other activities • Interoception: reduced satiety • Attention: bias toward drug-related stimuli • Learning and memory: disrupted ability to update the reward value of drug and non-drug reinforcers • Decision-making: delay-discounting; inaccurate predictions Operant Conditioning Model • Initiation of repeated use explained by benefits (e.g., decreased negative affect, increased positive affect, social affiliation) • e.g., GABAergic activity of alcohol • Has proven surprisingly hard to establish clear nomothetic links between affect and daily alcohol use, though (see Dora et al., 2022) • Tension reduction function of alcohol may depend in part on “alcohol myopia” • Attention more easily drawn to distractions → less attention focused on stress-inducing thoughts • Works when there are pleasant distractions, but drinking can increase negative affect when pleasant distractions aren’t present • Functionalist models of substance use emphasize question of whether people have alternative methods of attaining these benefits • Maintenance of use sustained partly by costs of cessation (e.g., desire to avoid withdrawal symptoms) Cognition: Drug Expectancies • People who expect alcohol to have stronger positive effects (and fewer negative effects) more likely to drink • Evidence that individual differences in alcohol expectancies are often already present in childhood • Tend to be fairly stable over time • Expectances can be inaccurate or incomplete, yet resistant to change Personality • Multiple personality dimensions predict onset of SUDs: • Negative affectivity • Desire for increased arousal and positive affect (novelty seeking) • Low constraint (e.g., high impulsivity) • These may be part of the pathway from genetics to symptoms • Some evidence that people with high impulsivity, novelty seeking may be more prone to sensitization (Boileau et al., 2006) • Not clear, though, that there’s really such a thing as an “addictive personality” (see, e.g., Griffiths, 2017) Boness et al., 2022 Family Factors • Parental alcohol use (genes, environments, or both?) • Modeling • Expectancies • Parental supervision and involvement • Marital discord, psychiatric or legal problems in the family, lack of emotional support from parents associated w/ increased use • Substance use also frequent source of conflict in families • Can become a vicious cycle Peer Factors • A lot of substance use is affiliative (think “social drinking”) • Substance use can increase sociability and confidence, reduce social anxiety • It’s often an activity that we share with others • It can be difficult to be sober if your closest friends are heavy drinkers (and vice versa) • Social influence or social selection? • There’s evidence for both pathways (e.g., Bullers et al., 2001) Environmental & Sociocultural Factors • Availability, attitudes toward, legalities of specific substances varies considerably from country-to-country • In the US, the gender gap in AUD has been shrinking over time • Stress (e.g., rates of unemployment, poverty, discrimination) and loneliness • Advertising and media • The consequences of cigarette ads may be more influential than peer pressure (Jackson et al., 2007) Developmental Pathways • There is a lot of heterogeneity in the “pathways” to (risk for) problematic substance use • An “internalizing” pathway? – inhibited temperament → internalizing symptoms (e.g., depression, anxiety) → desire for tension-reduction → substance use • Amplified in the absence of peer and parent support, lacking access to effective coping and emotion regulation strategies, life stress • An “externalizing” pathway? – uninhibited temperament → externalizing symptoms (difficulty regulating behavior, impulsivity, aggression, rule-breaking) → difficulties at school and home (e.g., disrupted relationships with peers, parents) → substance use Treatment Where do people receive treatment? • Only 18% of those with substance use disorders receive treatment from a mental health professional • Many people never receive treatment (stigma/shame, limited access, high cost) • Treatment is often at the behest of close others or compelled by courts What’s the goal? • Complete abstinence (e.g., AA & NA)? • Reduced or “controlled” use? • Harm reduction (e.g., needle exchange programs)? • Can make it tricky to conduct research on treatment “effectiveness” “Dialectical Abstinence” “Detox” • Particularly if withdrawal is a concern, first stage is often detox (hospital or home) • Can be medication-assisted • Gradual weaning vs. sudden cessation • Not an effective treatment on its own Medications • Aversion therapies (e.g., Antabuse for alcohol – only recommended as part of comprehensive programs d/t high rate of non-use) • Reducing cravings (e.g., Acamprosate for alcohol, Wellbutrin for nicotine) • Antagonists that block receptor binding (e.g., naltrexone for opioid overdose) • Replacement therapies (e.g., methadone, suboxone for opioids) • Opioid replacement therapies are politically very controversial Psychotherapy • Aversion conditioning therapy – not recommended • Motivational Interviewing • Cognitive behavioral therapies • Change cognitions that contribute to problematic use • Create a plan to reduce harm and use, potentially to the point of abstinence • Relapse prevention training • Identify cues for drinking, drug use; reduce cue exposure • Identify alternative strategies for coping with stress, anxiety • Treatment adherence can be enhanced through contingency management Residential Care • Reduced access to substances, exposure to peers who are using, substance-related cues • Frequent groups • Supportive role models • Can be very expensive • Not clear that intensive residential treatment is more effective than high quality outpatient care overall (NIDA, 2009) Treatment Considerations • Effective treatment attends to multiple needs of the individual, not just substance use • Essential to address reasons for using/factors maintaining use: • Environmental factors (e.g., stressors, finances, employment) • Social relationships (e.g., loneliness, lack of support, pro-use relationships) • Comorbid disorders (e.g., depression, anxiety) • Simply helping people quit using a substance likely not enough to produce sustained remission if the underlying material circumstances of their life remain unchanged Treatment Outcome Findings • More than half of people show gains with treatment, but… • Effective treatment can take a long time (3+ months), many undergo multiple rounds of treatment • Dropout, relapse rates are high • Effective treatment often not readily available or there may be substantial barriers (e.g., methadone replacement therapy) • Treatment is highly stigmatized • In other words, there’s a lot more work to be done! What about self-help programs? • AA/NA most common form of treatment • Abstinence focused – in the AA view, one is an “alcoholic” for life; “in recovery” synonymous with sustained abstinence • Reported effectiveness of AA based primarily on anecdotal info • AA does not directly participate in external comparative research • Emphasis on anonymity makes research challenging • Some attempts to conduct external RCTs, but methodologically challenging (e.g., people assigned to AA often don’t go) • Best data we have suggests that it’s probably helpful, but more work needed (Humphreys et al., 2014) Community-Based Prevention • Education- and skills-based programs • Harm reduction programs more promising than abstinence programs • “Anti-drug” campaigns can produce harmful effects • Skills training • For teens (e.g., to reduce effects of peer pressure) • For parents (e.g., Dishion & Kavanagh, 2003) • Laws and policies: public debate spans everything from efforts to further limit alcohol access for underage drinkers to efforts to decriminalize most substances and fund safe injection sites Final Thoughts • The human brain evolved with exquisite, powerful mesolimbic reward circuitry highly preserved • “Drunken monkey hypothesis” (Dudley) • Agnostic as to whether the sources of activation are survival necessities (food, water, shelter), substances that directly increase dopamine activity, or learned behaviors (e.g., gambling) • In the short-term • Substance use “retunes” our bodies, brains in ways that many people find increase pleasure, reduce discomfort • Substance use can provide access to socio-culturally valued people, places, and activities • Some intriguing, still mostly preliminary evidence of using hallucinogens as therapy adjuvants (e.g., MDMA for PTSD) • In the long-term • Substance use is reinforced and maintained by activation of dopamine circuits, brain changes that weaken prefrontal areas, creating the potential for people to engage in heavy use despite negative consequences More Final Thoughts • The brain is most vulnerable to the long-term effects of drugs during periods of accelerated development (e.g., prior to birth, during adolescence) • Fetal alcohol syndrome • Cannabis and schizophrenia • Historically, substance use has often been separated out from other psychopathologies (e.g., SAMSHA) • Some evidence that SUDs are even more stigmatized • Changing the language of addiction