PSYC62 LEC 6 Drug Use and Addiction - Lecture Notes PDF

Week 6 (Drug Use and Addiction) Drug Addiction: A Complex Behavioral and Neurobiological Disorder with risk factors Historical ○ - Prior experience ○ - Expectation ○ - Learning Environmental ○ - Social interactions ○ - Stress ○ - Conditi...

Week 6 (Drug Use and Addiction) Drug Addiction: A Complex Behavioral and Neurobiological Disorder with risk factors Historical ○ - Prior experience ○ - Expectation ○ - Learning Environmental ○ - Social interactions ○ - Stress ○ - Conditioned stimuli Physiological ○ Genetics ○ - Circadian rhythms ○ - Disease states ○ - Sex Why do people consume drugs? to feel good - novel feelings, sensations, experiences, social affiliations and to share them with others to feel better - lessen anxiety, worries, fears, life burdens, depression, and hopelessness Drug Use in Canada: Two surveys Highest use group is ages 20-24 “Any of 6 drugs” are illicit drugs Declines over time, why? ○ potential for overdose ○ drugs are presented in the media and around that time people are trying to establish an identity for themselves other survey Ages 15 and over Licit drugs widely consumed are alcohol, caffeine, tobacco C: What do you conclude from this data? ○ alcohol is very available Consumption trends of recreational drugs Recreational drugs are widely consumed in North America ○ Illicit psychoactive substance consumed voluntarily, has the potential to be used in problematic way 275 M surveyed, 12 years & older  Illegal drug use in the USA is mostly cannabis primary demographic are young adults “Good” versus “bad” drugs is largely determined by society, so how are “bad” drugs controlled? Historical Perspective on drug use and policy Psychoactive drug use 10,000 year ago; opium prescribed 8,000; cannabis use 7,000, cave art depicts mushrooms 6,000 For most of the time: ○ drugs were derived from naturally occurring, organic, substances ○ drug use was governed mostly by social conventions But technological developments brought changes 300 years ago drugs were tobacco, alcohol, caffeine, opium 19th century chemical and medical innovations of purification of morphine from opium, cocaine from coca, and hypodermic needle Temperance movement equated drug use to criminal acts (policy) Purified drugs in non-regulated patent medicines (policy) Late 20th century a movement for medical diagnosis of drug addiction (policy) History of Canadian Drug Policy 1908 - have to list the ingredients that you are putting in 1911 - cocaine and opium possession 1900s-1920s - alcohol started becoming more common 1929 and 1961 - increased the amount of punishment for possessions 1996 - the drug being prescribed must have to do with the danger the individual may pose to society 2016 - Canadian Drugs and Substances strategy prevention; treatment; harm reduction; enforcement ○ target organized crime those who distribute drugs 2018 - cannabis act C: Do we need drug policies? ○ Informative for people to understand the drugs Canadian Federal Drug Laws Health Canada: Controlled Drug and Substances Act (1996) ○ Replaced the Narcotics Control Act (1961) Had 8 schedules of controlled substances (do not have to memorize) ○ Schedule 1: heroin, cocaine, methamphetamine, morphine, etc. ○ Schedule 2: marijuana and derivatives ○ Schedule 3: LSD, mescaline, psilocybin, etc. ○ Schedule 4: anabolic steroids, barbiturates, benzodiazepines  ○ as schedules get higher they start becoming more harmful and dangerous Cannabis Act (2018) repealed Schedules 2, 7, 8 How are substances assigned to different schedules? Listed in order of potential risk ○ Does it have a current accepted medical use? ○ Relative abuse or misuse potential? ○ Likelihood of causing dependence when abused? C: Where are alcohol, caffeine, tobacco? How would you schedule them? ○ not on there because they are legal Drug Schedules and Science UK system schedules drugs in descending classes A, B, C Classed according to actual or potential harm they produce Nutt et al. (2007) investigated drug harms (0-3) based on: ○ higher number meant highest risk C: If classes are based on harm, what data pattern would you expect to see? What is Drug Addiction Drug addiction and drug dependence are not the same Early views emphasized physical dependence C: Issues? (Some drugs don’t cause physical dependence) ○ Tolerance developed and abstinence produces withdrawal symptoms Modern conceptions emphasize behavioral aspects of: ○ Craving: a strong urge to take the drug C: Issues? ○ Relapse: return to drug use after a drug-free remission period, despite negative consequences C: Issues? (Some people may be lactose intolerant or asthma medication) “Drug addiction can be defined as a chronically relapsing disorder, characterized by compulsion to seek and take the drug, loss of control in limiting intake, and emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) when access to the drug is prevented” (Koob and Volkow 2016) Definitions by fundamental researchers may not fully encapsulate this complex phenomenon → DSM-5 Diagnostic Criteria of Psychiatrists American Psychiatric Association does not use addiction or addict terms, instead the DSM-5 specifies a group of substance-related disorders Characterized by significant substance misuse (no longer refers to substance abuse or dependence)  ○ “a cluster of cognitive, behavioral, and physiological symptoms indicating that the individual continues using the substance despite significant substance-related problems” Covers 10 drug classes: alcohol, caffeine, cannabis, tobacco, hallucinogens, inhalants, opioids, sedative-hypnotics / anxiolytics, stimulants, other substances Provides specific set of criteria to diagnose substance use disorder for 8 classes (caffeine and other substances not included) Diagnostic of Psychiatrists DSM-5 provides specific criteria for different levels of substance use disorder The pattern of use must be problematic and lead to clinically significant impairment or distress in past 12 months Mild substance misuse consists of 2-3 symptoms ○ 55 different combinations for 2 symptoms Moderate substance misuse consists of 4-5 symptoms ○ 330 different combinations for 4 symptoms Severe substance misuse consists of 6 or more symptoms ○ 462 different combinations for 6 symptoms A diversity of behaviors can be singularly classified as substance use disorder Behavioral addictions in the DSM-5 are categorized as non-substance-related disorders ○ Gambling disorder is the sole entry C: Does the behavior reach a threshold as psychopathology? C: Do the features align with DSM-5 SUD criteria, or is it an impulse control disorder? Theories of Drug use progression Gateway theory: recreational drug use in adolescence increases the risk of progressing to other substances Based upon a longitudinal study in New York from the 1960s Empirical support: (for gateway theory) ○ Rats given water or nicotine for 7 days ○ Receive saline or cocaine for 4 days ○ Track locomotion after last injection ○ On the last day they give either saline or cocaine ○ increase in their locomotion C: What is the interpretation of this graph? ○ Water is basic control ○ Increase in locomotion ○ pre-exposure to nicotine to cocaine is higher due to the characteristics of nicotine Problematic use theory: recreational drug use can be patterned, but only a subset of users progress to compulsive and loss of control use  People experiment with drugs and addiction does not develop Many substance users reduce use in adulthood due to lifestyle responsibilities, but not all follow this “maturing out” progression Becomes problematic when a cycle of use begins that includes elevated use, withdrawal, tolerance, decreased euphoria, loss of control, compulsion Addictiveness of drug and misuse potential capture ratio: the number of people who try the drug divided by the number who become regular or habitual users Rating: 1 is most serious, 6 is least ○ Criteria are withdrawal, tolerance, reinforcement, dependence, intoxication C: What could influence these measures? ○ route of administration Route of administration and misuse potential Oral and transdermal administration has relatively slow drug absorption, whereas intravenous (IV) injection and inhalation have fast drug onset Fast drug absorption: strongest euphoric drug effects AND shortest latency (duration) between drug consumption and euphoric effect These characteristics important for associative memory formation We can’t measure addiction in rodents, but we can look at how reinforcing and rewarding drugs are  Positive reinforcers: Consuming drugs strengthens the behavior that preceded consumption Drug reward: positive subjective experience of the drug Place Conditioning: Drug Reward Drug conditioning: Pair drug with place A Vehicle conditioning: Pair vehicle (usually saline) with place B Test of preference: animal freely explores the two environments Time spent in drug paired context equated to reward ○ Whichever the strongest drug is (methadone and cocaine example) ○ Whichever drug was more rewarding Drug self-administration: reinforcement Operant variations ○ Continuous reinforcement (CR) ○ Fixed ratio (FR-10) ○ Progressive ratio (PR-2) ○ Fixed interval (1 minute) ○ Variable interval (1-10 minutes) When drug is available the the rats press a lever and the light comes on Light associated with infusion of drug and presing the lever An operant response on a lever delivers IV drug Model of reinforcement learning for drug-seeking, drug-using behavior Drugs readily administered are cocaine, heroin, amphetamine, meth ○ Increasing the does = more lever pressing Drugs not readily self-administered have lower addiction potential Electrical self-stimulation: reinforcement/reward Reduction of self-stimulation threshold after drug administered is a measure of drug’s rewarding properties Responding during withdrawal is a measure of withdrawal severity are going to press less if the drug is already making them feel rewarded Self-administration behavior Inverted-U shape dose-response ○ Why? Multiple factors such as satiation(have enough drug on board), aversive reactions, behaviourally disruptive side-effects Drugs and doses with high response levels and high breakpoints have misuse potential PR breakpoint (first CR, then FR) ○ pressing a lever and work a lot more to get the same dose of the drug  Higher breakpoints are positively related to drug dose Self-administration is not a model of drug misuse or addiction Self-administration: extinction and reinstatement Stable IV SA is followed by forced abstinence during extinction period Reinstatement is precipitated by drug priming, stress exposure, or cues previously related to drug availability ○ Influences misuse potential ○ press the level and do not receive the drug and there are lesser responses Extinction and reinstatement model aspects of drug relapse ○ Cues like showing the light or stressor or small dose of drug How do we conceptualize patterns/cycles of drug use in humans, what is the theory? Severity of withdrawl symptoms and misuse potential Theoretical model: chronic drug use can lead to withdrawal symptoms that are so intense the user relapses to alleviate them (preventing abstinence) Negative reinforcement model (removal of undesirable stimulus) Le Moal & Koob theory ○ Impulsive stage is positive reinforcement ○ Compulsive stage is negative reinforcement ○ “Dark side” of addiction is the negative effect of withdrawal Risk factors for misuse potential and affect many Heritability of substance use disorder ranges from 40-60%  Psychosocial: increased risk with younger age, less education, non-white racial background, lack of employment, and childhood misconduct Stress: frequency and severity of stressful life events and the individual’s ability to cope with such events Comorbidity: diagnosis of anxiety, mood, or personality disorders in addition to substance abuse disorder ○ self-medication for anxiety or trauma Sex: men begin in social groups and women in response to negative life events ○ Women escalate faster and relapse-sensitive to context cues Protective Factor Absence of risk factors reduces development of addiction For people in addiction recovery: ○ a support network, maintaining a stable lifestyle, sources of reinforcement outside of drugs, and acquiring coping mechanisms for stress NESARC longitudinal study of 34,653 people self-reporting that after three years ○ 67% of asymptomatic users became nonusers ○ 49% of problem users became nonusers Natural recovery: transitioning from substance misuse or addiction to non-problematic use or nonuse without assistance Biopsychological model for drug addiction factors can promote compulsive drug seeking and drug-use few protective factors Development of addiction Simplified conceptualization in 3 cyclical stages that satisfies DSM criteria and aligns with Le Moal and Koob theory How do we enter this cycle? Mechanisms driving intoxication? Drug reward and Binge/intoxication stage Brain did not evolve for the purpose of mediating drug reward, rather to signal naturally motivating stimuli for survival Our brain is wired to pay special attention to salient things—special relevance including threats, food, sex, water ○ Recreational drugs capitalize and co-opt this neurocircuitry Dopamine in the VTA is important Opioid peptides Recall burst firing characteristics of DA neurons fMRI in humans for money reward ○ Medial prefrontal cortex, NAc, VTA light up (dopamine increase) Rodent natural rewards with food ○ Dopamine increase when food given Incentive Salience Theory A hypothesis for how drug-related stimuli gain increased prominence and attractiveness Drug addiction is a transition from liking to wanting ○ Liking: hedonic signaling the drug produces ○ Wanting: a motivation to seek the drug Incentive salience develops because liking reduces, but the incentive to seek the substance becomes the salient feature because wanting mechanism/process became amplified (your body needs it?) ○ drug itself is decreasing but the individual motivation is increasing having impact Liking: supported by hedonic hotspots in the NAc activated by endogenous opioids and endocannabinoids (mediate the experience of pleasure), lessens with drug usage (becomes desensitized reducing pleasure) Wanting: supported by dopamine from VTA in NAc, increases with drug usage Reward Prediction Error A hypothesis that dopamine levels in the NAc are elevated when a stimulus is higher or lower than expected ○ when the conditioned stimulus is paired with a reward you know that there will be a reward ○ No way to predict when the conditioned stimulus comes on The thing that is predicting the reward that produces dopamine firing not the reward itself Variety of data supports liking/wanting and prediction-error theories Withdrawl/negative affect stage  Hyperkatifeia (aka allostasis) distressing emotional and motivation state that mounts with increasing drug use…it is a reward deficit not directly withdrawal symptoms It represents dysphoria, irritability, symptoms of ill at ease, uncomfortable within one’s own skin, not hedonically normal Addicts report the need to take more drug to feel “normal” or “high” Origin of theory from conceptual framework of affective dynamics construct of opponent process: ○ What goes up, must come down in the hedonic arena Drug produces (+) A-process in hedonia; once drug metabolized an opposing (-) B-process of dysphoria ○ Goes into a negative process before going to baseline ○ does not go directly to baseline, but does go eventually Putting it together with 3-stage model Reward is the “Binge intoxication stage” ○ Theory: incentive salience and/or prediction error, pathological habit formation ○ Region: Striatum Relief is “withdrawal / negative affect stage” ○ Theory: reward deficits and sensitized anti-reward system (hyperkatifia stage) ○ Region: Extended amygdala Relapse is “preoccupation” stage ○ Theory: Loss of control, craving, and compromised executive function ○ Region: prefrontal cortex Neural Correlates of “reward” and “relief”  NAc-mediated reward pathway for positive reinforcement of behavior ○ Becomes down-regulated Dependent ○ Becomes up-regulated ○ Circuit of NE and corticotropin releasing factor (CRF) and amygdala for negative reinforcement; limits reward processing, hyperkatifeia Preoccupation stage of the 3 stage cycle Addiction requires a conscious evaluation of the effects of drugs and planning to obtain them Prefrontal cortex is implicated in executive functions including planning, problem solving, cognitive flexibility, valuation, and emotional regulation Prefrontal cortex hypothesized to have a role in intrusive thoughts for drug craving AND loss of behavioral control Insula is critical for interoceptive evaluation of stimuli and craving This “Go” or “Stop” system undergoes neuroadaptation with drug taking to enhance “Go” and reduce “Stop” Intrusive thoughts and craving circuitry Preoccupation to obtain drug because of increased drug craving Intrusive thinking is associated with dysfunction of VMPFC and amygdala projections to the NAc Cue induced craving is associated with insula, dorsal and ventral striatum, and many prefrontal subregions Is addiction a brain disease? Widely accepted disease model of addiction states drug misuse produces enduring changes and brain dysfunction ○ AKA medical model and enables health insurance coverage Moral model states addiction is a personal and moral problem ○ Brain alteration alone does not prove that addiction is a disease, question is whether it is pathological change ○ There is no single diagnostic test to confirm a substance use disorder should have a biomarker for it ○ Empirical evidence raises doubt that heavy drug use is outside the user’s control ○ Drugs serve the purpose of alleviating emotional pain, lack of positive reinforcers, or available reinforcers fail to provide sufficient motivation ○ Focus on the psychosocial roots of drug taking behavior to treat the person as a whole Importance of Alternative Reinforcers Rat park studies by bruce alexander large arena containing: ○ other rats (males and females) ○ running wheels ○ novel objects ○ morphine and water bottles What does this graph show? ○ more caged females in morphine consumption and choice days