Drugs and Addiction Lecture Notes PDF

Topic 5 Drugs and Addiction • Therapeutic Drugs • Drugs of Abuse • Drug Abuse Models • Factors Driving Addiction Freedom of Compulsions Habits and Addictions – Paulo Zerbato Psychoactive drugs Drugs that act on the CNS, alter normal function. • Therapeutic drugs • Drugs of abuse Four major clas...

Topic 5 Drugs and Addiction • Therapeutic Drugs • Drugs of Abuse • Drug Abuse Models • Factors Driving Addiction Freedom of Compulsions Habits and Addictions – Paulo Zerbato Psychoactive drugs Drugs that act on the CNS, alter normal function. • Therapeutic drugs • Drugs of abuse Four major classes of therapeutic drugs: • • • • Antipsychotics Antidepressants Anxiolytics Analgesics Schizophrenia Schizophrenia – mental illness characterized by psychosis (difficulty differentiating between real and not real) Positive symptoms hallucination, delusions Negative symptoms - social withdrawal, blunted emotion Antipsychotic (neuroleptic) drugs Older drugs (first-generation) typically selective antagonists for DA D2 receptors. • Primarily relieves positive symptoms Newest antipsychotics (second-generation) block D2 receptors along with others (like 5-HT) • Some limited ability to relieve negative symptoms Antidepressant drugs Earliest drugs: monoamine oxidase (MAO) inhibitors  prevent degradation of monoamines • Problem: MAOIs interacted w/tyramine-rich diets, greatly  stroke risk Tricyclic antidepressants block reuptake of 5-HT and NE. • Problem: tricyclics block Na+/Ca2+ channel at high doses  dangerous! Antidepressant drugs Modern antidepressants blocking reuptake of specific monoamines • selective serotonin reuptake inhibitors (SSRIs) – specific to 5-HT (Prozac, Zoloft, Celexa) • serotonin-norepinephrine reuptake inhibitors (SNRIs) – targets both 5-HT and NE (Effexor) Anxiolytic drugs Treat anxiety disorders Function as CNS depressants • Typically GABAA agonists Barbiturates (sedative-hypnotics) – earliest drugs • Very effective, but addictive and dangerous Benzodiazepines (benzos, tranquilizers) - safer alternatives • Alprazolam (Xanax), Diazepam (Valium), Chlordiazepoxide (Librium) SSRIs and SNRIs also have anxiolytic properties (curb day-to-day anxiety) Analgesic drugs (painkillers) Opioid drugs - directly block pain signals from the body • Work on same receptors as endogenous opioids (enkephalins, endorphins, dynorphins) • Three main types of opioid receptors: mu (μ), delta (δ), kappa (κ) Cannabinoids Cannabis plant produces several psychoactive drugs, including: • Delta-9-tetrahydrocannabinol (THC) • Cannabidiol (CBD) Bind to cannabinoid receptors • endogenous cannabinoids! (anandamide) THC active ingredient often used recreationally Effects - relaxation, mood alteration, stimulation, and paranoia Used to treat multiple sclerosis, pain, nausea/vomiting (chemo), anorexia, arthritis Adolescent use  increased risk of schizophrenia • causal or correlational? Legal status of cannabis as of 09/23 Recreational Medical Illegal Decriminalized CBD Less-psychoactive cannabinoid • Claims of anxiolytic, antipsychotic, antiepileptic effects • Only approved by FDA for treatment of epilepsy Most claims are wildly hyperbolic and unsubstantiated. Stimulants Increase neuronal activity by increasing excitatory input or decreasing inhibitory activity usually by acting on monoamine systems Stimulants include: • Nicotine • Cocaine • Amphetamine (and related drugs) • Many more Stimulants Generally: Low doses improve cognitive performance. • Sharpen cognition, improve memory, focus attention • Ex: ADHD medications Moderate/high doses cause euphoria, reduced cognitive function, highly addictive • Ex: cocaine, amphetamine Nicotine Agonist at nicotinic ACh receptors (nAChRs) • nAChRs in prefrontal cortex (mesocortical) • Cognitive enhancement • nAChRs in ventral tegmental area (VTA), nucleus accumbens, amygdala (mesolimbic) • Reward/addiction Cocaine Extremely addictive! Blocks monoamine reuptake Effects: euphoria, increased heart rate/blood pressure • Prolonged/heavy use: aggression, psychosis, irritability, hyperawareness Amphetamine Four step-mode of action on monoamines: 1. Reverses monoamine transporters in membrane, vesicles  DA pumped out of vesicles into synapse 2. Amplified monoamine release after APs 3. Blocks monoamine reuptake 4. Provides alternative target for MAO Amphetamine Short-term effects: increased vigor/stamina, wakefulness, decreased appetite, euphoria Quick development of tolerance and addiction Prolonged use: MDMA-induced neurotoxicity in nigrostriatal DA pathway • schizophrenia-like psychosis • compulsive, agitated behavior • autonomic symptoms (high BP, sweating, rapid breathing), • neurotoxicity Granato et al, 2008) Methamphetamine, MDMA (ecstasy) and other amphetamine-like drugs are typically more potent Alcohol Alcohol effects are biphasic –initial stimulant phase followed by a depressant phase. • Stimulant - activation, social disinhibition • Depressant – sedation, motor/cognitive impairments Acts via GABAA  indirect effects result in increased DA release • Alcohol effects are complicated! Fetal alcohol syndrome – permanent fetal damage resulting from alcohol abuse during pregnancy Hallucinogens LSD strongly activates 5-HT receptors • Effects: mood changes, creativity, sensory disturbances • May help treat some psychiatric disorders. Mescaline (hallucinogenic cactus) and psilocybin (magic mushrooms) are naturally-produced hallucinogens MDMA (Ecstasy) - hallucinogenic version of amphetamine • Both stimulant and hallucinogenic effects • Activates both 5-HT and DA systems Addiction models Moral model Disease model Physical dependence model Positive reward model Addiction models Moral model – user lacks moral character or selfcontrol • Promotes self-blame, self-hatred, and powerlessness Addiction models Disease model - user requires medical treatment • No blame, but responsibility • Disease is lifelong, progressive • Must submit to “higher power” • God (12 step programs (AA, NA) • Treatment program (rehab, support groups) Addiction models Physical dependence model – drug use to avoid withdrawal symptoms • unpleasant sensations when drug use stops Withdrawal symptoms opposite of drug’s normal effects Opioid drug effects Opioid withdrawal symptoms Sedation Agitation, insomnia Pain relief Increased pain sensitivity Enhanced pleasure/happiness Severe dysphoria (unpleasant feelings), depression Constipation Diarrhea Addiction models Positive reward model - drug use compelled by positive reward sensations • Self-administration experiments show addiction can occur without physical dependence or withdrawal symptoms Addictive drugs directly or indirectly activate VTA neurons, causing DA release into the nucleus accumbens (NAcc) DA in NAcc  motivational thrust The Power of Positive Reward What really causes addiction? Biology – genes make up about half of risk • Effects of gender, ethnicity, mental illness Environment • • • • • Social influences (peer pressure) Physical/sexual abuse Early drug use Stress Parental influence Personality – aggressiveness, emotional control abilities Development – interaction of genes x environment • Early use = higher addiction potential (esp. teens!) No one factor is perfectly predictable What drives drug use? Environmental stimuli can become associated with the effects of drugs. Cue-induced drug use - increased likelihood of drug use because factors are present that were also present when the drug was last used. A completely different take on addiction Is something else entirely driving addiction? Note: Rat Park experiment is overly simplified/exaggerated in video. Small number of rats get addicted regardless of connection/social factors! How can we treat it? Prevent it from occurring in the first place! Behavioral therapies Medication No single treatment is most effective • Address medical, social, psychological, vocational, legal problems of user Treatment needs to be readily/easily available! Your action items (9/14) Quiz likely coming soon… Exam 1 is 2 weeks from today! Coming Up: • Tuesday: T6: The Endocrine System and Hormones • Thursday: T7: Sensory Systems