Lecture 4 Psychopharm Tolerance and Dependence 2020 PDF

Psychopharmacology Tolerance and Dependence: The long-term effects of drug use  What is Tolerance? Tolerance: Decreased susceptibility (or diminished response) to the effects of a given drug as a result of previous exposure...

Psychopharmacology Tolerance and Dependence: The long-term effects of drug use  What is Tolerance? Tolerance: Decreased susceptibility (or diminished response) to the effects of a given drug as a result of previous exposure Tolerance is not uniform King Mithridates VI across all effects of a drug Mithridatism ❖King of Pontus (120–63 BC) Opioid Tolerance ❖Cultivated immunity to all poisons by daily sublethal doses Major component in ❖After series of war defeats, addiction and loss of control attempted suicide by poisoning NOW… ❖His assistant had to decapitate Individual must take more of him with a sword. drug to achieve similar effect Generally considered to be a long-term change introduced by continued use  Types of Tolerance Pharmacokinetic Pharmacodynamic Context-Specific (Metabolic or (Functional or (Behavioral) Dispositional) Associative) Tolerance Tolerance Tolerance Tolerance involves multiple short-term and long-term changes in bodily and brain processes Types of Tolerance: Pharmacokinetic (Metabolic) Tolerance produced by an increase in the rate of drug metabolism “What the Regular Consumption body does to Largely the drug” mediated by Increased Metabolic Activity increased cytochrome P450 enzymes More Reduction in Less Drug to Rapid Drug in Sites of Action Removal Systemic Circulation Net Result ❖Lower concentrations of drug after the same dose ❖Effect is less intense and of shorter duration ❖Individuals take more!  Types of Tolerance: Pharmacodynamic Tolerance produced by decrease in nervous system sensitivity to the drug “What drugs do to the 2. Changes in Receptor Site Populations body” ❖Up-Regulation ❖Increased Number of Receptor Sites 1. Changes in ❖Commonly seen with Antagonists. Neurotransmitter ❖Down-Regulation Levels ❖Decreased Number of Receptor Sites ❖Changes in ion channels ❖Commonly seen with Agonists. ❖Decreased NT synthesis ❖Depletion of NT reserves 3. Changes in Receptor Site Sensitivity ❖Sensitization. Commonly seen with Antagonists. ❖Desensitization. Commonly seen with Agonists. Thus, the same concentration of drug produces less impact on bodily systems Types of Tolerance: Context-Specific (Behavioral) Learning effects can dramatically influence the overall drug experience Classical (Pavlovian) Operant (Skinnerian) Conditioning Habituation Conditioning The brain (and thus the body) learns from prior experiences  Associative Learning: Classical Conditioning How it works: After repeated exposure to two stimuli occurring in sequence, we associate those stimuli with each other. Result: Our natural response to one stimulus now can be triggered by the new, predictive stimulus. Before Repetition After Repetition Thunder Cover Ears Lightning Cover Ears Here, our response to thunder becomes associated with lightning. Stimulus 1: See lightning Stimulus 2: Hear thunder  The Basics of Classical Conditioning ❖Learning of the association between an event and the circumstances (“cues”) preceding (or predicting) the event ❖One of the most universal forms of learning ❖Starts with a natural reflex of the body Cue Event Response  Classical Conditioning and Drug Use Drugs Possible CSs (“Triggers”) Possible CRs ❖Any stimulus associated with drugs ❖ Anticipatory CRs: cravings, anticipation ❖Drug paraphernalia, money, bars, friends, etc. ❖ Compensatory CRs: changes in body state  Classical Conditioning Behavioral Therapy Approaches Conditioned Aversion Therapy Cue Exposure Therapy ❖Extinction approach that attempts to break the association between CS and CR by repeated exposure of CS only ❖Clients are exposed to drug triggers but stopped from using drug Antabuse + Alcohol = nasty gastric consequences. Patients quickly learn to avoid alcohol. Does It Work??? Medication Noncompliance Do It Work??? No, Not Really. ❖Generalizability of cues: Results don’t extend to real world Yes and No. ❖ Spontaneous recovery  Basics of Operant Conditioning Learning of the association between an event and the consequences of that event Response: balancing a Consequence: receiving Behavior ball food strengthened Reinforcers Any consequence that increases the probability the behavior will occur again. Punishers E. L. Thorndike Any consequence that decreases the probability the 1874-1949 behavior will occur again. Simply put, Behavior is determined by its consequences  Behavioral Consequences: Reinforcers Reinforcers Any consequence that increases the probability the behavior will occur again. Positive Reinforcers Any stimulus whose presentation is reinforcing (Providing something good!) Negative Reinforcers ❖ Any stimulus whose removal is reinforcing (Taking away something bad!) What Do You Work For in Life???  Reinforcers in Drug Use and Addiction Positive Reinforcers Negative Reinforcers “Whole-Body Orgasm” Reduction of anxiety Euphoria Avoidance of stressful situations Self-confidence Self-medication Feelings of high Release from unpleasant emotional state Warmth Release from abstinence syndrome Solomon’s opponent-process theory ❖ Initial use is driven by pleasurable effects. ❖ These effects decrease over time (tolerance) ❖ Now, users use to avoid the negative consequences of not taking drugs (abstinence syndrome, cravings, facing problems created by use, etc). ❖ End Result: Addiction (Compulsive use without necessarily enjoying it).  What is Dependence? Dependence: Continued drug use that results in uncontrollable and unpleasant mood states which drive compulsive use despite the adverse consequences DSM5 Criteria Tolerance Withdrawal Cravings Uncontrolled Use Use despite Adverse Consequences Dependence: has both physical and psychological components.  The Addiction Severity Index The ASI is a semi- structured interview designed to address seven potential problem areas in substance-abusing patients: medical status, employment and support, drug use, alcohol use, legal status, family/social status, and psychiatric status. Interviewer Severity Ratings of Two Patients Admitted to Drug Abuse Treatment: An Opiate-Dependent Physician (light bars) and a Cocaine-Abusing, Pregnant Woman. From McLellan et al., 2006  Components of Dependence Psychological Dependence Physical Dependence What It Is Strong compulsion to use drug because of its Abstinence or Withdrawal Syndrome reinforcing consequences ❖ Physical state resulting from cessation of drug ❖ Positive Reinforcers: Feeling High ❖ Withdrawal symptoms are opposite of the drug’s effects ❖ Negative Reinforcers: Aversive Control ❖ Effects are severe enough to promote use to treat or prevent withdrawal symptoms Examples Solomon’s opponent-process theory Heroin: runny nose, chills and fever, inability to sleep, hypersensitivity to pain, diarrhea Brain May be mediated by reward circuitry of brain Withdrawal syndrome results from the disruption of bodily Mechanisms ❖ mesolimbic dopamine system mechanisms because of tolerance. ❖ glutamate system (perhaps) Different Drugs Have Different Abstinence Profiles Treatment of Dependence from a Biopsychosocial Model Stop withdrawal symptoms ❖Supportive Care ❖Naloxone for narcotic withdrawal ❖Empathy ❖Rapid detoxification ❖Psychotherapy ❖Fixing Relationships ❖Addressing Triggers ❖Understanding Social Network Medication-Assisted Treatment ❖Satisfy symptoms through Cross-dependence (taking one drug to satisfy dependence needs of another drug) ❖Can be short-term or long-term (lifetime) ❖Allows normal functioning despite dependence ❖ Often, the first line of treatment  Treatment of Alcohol Dependence Symptoms The special case of ❖Overactivity of the nervous system Delirium tremens usually beginning within 6 to 48 hours ❖Severe agitation, confusion, ❖Tremors, nausea, weakness, seizures, delirium, terrifying tachycardia (fast heart rate), etc. hallucinations ❖Can last a week or so ❖Large increases in heart ❖A hangover is an acute version rate, breathing rate, pulse, and ❖What helps? blood pressure ❖Can be life-threatening Complications ❖ Co-morbid health problems ❖ Electrolyte and vitamin deficiencies ❖ Mental Illness Issues ❖ Dementia Issues Alcohol Withdrawal can be Life-Threatening  Treatment of Alcohol Dependence Supportive care ❖ Keep ‘em comfortable! ❖ Quiet environment, reduced lighting ❖ Limited interpersonal interaction; reduced sensory stimulation ❖ Proper nutrition and fluids ❖ Reassurance, encouragement Pharmacologic interventions ❖Benzodiazepines: Alleviate withdrawal symptoms through cross- dependence (Serax, Ativan) ❖Adrenergic medications: Reduce overactive autonomic activity (clonidine, propranolol) ❖Antiseizure medications: Treat seizures and overactivity (Tegretol, Depakene)