Psychopharmacology of Addictive Behaviour (PYB260) 2024 Lecture Notes PDF

PYB260 PSYCHOPHARMACOLOGY OF ADDICTIVE BEHAVIOUR Sem 2, 2024 Week 12: Action & Effects of Opiates Melanie White, QUT  Lecture Outline What are opiates? History Administration, distribution & excretion Effects of opiates – physio...

PYB260 PSYCHOPHARMACOLOGY OF ADDICTIVE BEHAVIOUR Sem 2, 2024 Week 12: Action & Effects of Opiates Melanie White, QUT  Lecture Outline What are opiates? History Administration, distribution & excretion Effects of opiates – physiological & performance Conditioning, tolerance & withdrawal Harmful effects Pharmacotherapies for opiate/opioid disorders  Reflection Questions (egs, not exhaustive) Explain all the ways that heroin differs from morphine How are the ‘opiate receptor like’ receptors (ORL1) similar & different to the other 3 types of (typical) opiate receptors? How do opiates have their effects upon binding to typical opiate receptors? How do the effects differ by receptor type? Which brain regions are thought to underlie the effects of opiates on a) reinforcement, b) physical dependence & c) respiration? What are some of the key differences in psychopharmacological properties of synthetic opiates used to treat opiate addiction vs. other opiates Describe some of the moderating factors affecting mood effects Describe pattern of effects of opiates on unconditioned behaviour and conditioned behaviour in rodents What are opiates/opioids? & The history of their use  What are opiates: overview? Opium Opiates/Opioids (opium-like substances) Morphine & codeine (opium derivatives) Heroin (modified (semi-synthetic) morphine derivative) Synthetic opiates (e.g., meperidine/ pethidine (Demerol), methadone, dextromethorphan) Endogenous “opiates”  What are narcotics? Opiates aka narcotics or narcotic analgesics Narcotic analgesics: sensitivity to pain & sleep Opiates must meet the following criteria: 1. Sedative-hypnotic & analgesic properties 2. Acts on endorphin/enkephalin receptors 3. Actions antagonized by naloxone (Narcan)  What are opiates? Opium: extracted from poppies active ingredients in seedpod sap 2 main active ingredients: 1. Morphine 2. Codeine  Table 11.1 Opioid Drug Formulations & Routes of Administration Routes of Opioid Drug Administration for Common Recreational Pharmaceutical Routes of Administration Formulations Oral (tablet, capsule); Morphine Rectal (suppository); Injected, swallowed, Parenteral (i.v., i.m., smoked s.c. injectable solution) Parenteral (i.v., i.m., Heroin s.c.)* Injected, snorted, smoked Oral (tablet, capsule, Injected, swallowed (often Codeine syrup); Parenteral (i.m., mixed with soda or s.c. injectable flavorings) solution) Oral (tablet, capsule, Hydrocodone syrup) Injected, swallowed, snorted Source: Textbook, Fig 11.1  What are opiates? Heroin: derived from morphine “semi-synthetic” opiate 10 X more lipid soluble vs. morphine = faster absorption in  concentrations  What are opiates? Synthetic opioids: opiate-like effects (stimulate opioid receptors) but different chemical structure Egs: Meperidine (pethidine), fentanyl, dextromethorphan (cough mixtures; “roboing”) & LAAM  History of Opiates 6000 BC – West Mediterranean cultivation 1300 BC – Egypt 200 BC use spread through Middle East 460 BC Hippocrates - Medical uses 400 AD introduced to China from Arab traders  History of Opiates 1680 Sydenham produces Sydenham’s Laudanum – opium, sherry, wine & herbs 1700 Chinese began smoking opium rather than tobacco 1767 – import of opium to China = 2000 chests/year 1793 – British East India Co. has monopoly on opium trade 1825-1875 British opium consumption   History of Opiates Morphine becomes available on prescription 1839 - 1841 – First Opium War 1843 – Dr. Alexander Wood discovers injecting morphine 1856 – 2nd Opium War 1874 – heroin synthesized by C.R. Wright 1890 – US impose tax on opium & morphine  History of Opiates 1895 – Dreser ‘invents’ heroin 1898 – heroin marketed by Bayer 1900’s – St. James Society campaign for free heroin for morphine addicts 1905 – US congress bans opium 1910 – Chinese succeed in dismantling the India-China trade 1914 Harrison Narcotic Act bans morphine, opium & cocaine  US “Opioid epidemic” https://www.cdc.gov/overdose-prevention/about/understanding-the-opioid-overdose-epidemic.html?CDC_AAref_Val=https:// www.cdc.gov/opioids/basics/epidemic.html  2022–‍2023 National Drug Strategy Household Survey (NDSHS) Figure 1: Summary of alcohol, tobacco, e-cigarette, and illicit drug use, people aged 14 and over, 2022–‍2023 https://www.aihw.gov.au/reports/illicit-use-of-drugs/national-drug-strategy-household-survey/contents/summary www.acic.gov.au/sites/default/files/2024-07/Queensland%20%E2%80%93%20Report%2022.pdf Administration, absorption, distribution & excretion of opiates  Administration, distribution & excretion Morphine: a base with pKa of 8.0 → less effective when taken orally (vs. injection) With oral administration: undergoes significant first pass metabolism (liver) absorbed slowly (but may be desirable if taken for analgesic properties)  Refresher: Ionization of drug molecules pKA Theoretical curve for weak base with pKA=8 (adapted from McKim & Hancock, 2013, Fig. 1-7, p.15)  Administration, distribution & excretion Heroin: Usually injected Can be taken intranasally (snuff) Inhaled (chasing the dragon)  Administration, distribution & excretion Distribution Most opiates concentrated in heart, lungs, kidney, liver, spleen, & bound to proteins in blood Pass through placental more readily than blood-brain barrier (low lipid solubility) An exception: Heroin is highly lipid soluble  easily enters brain Within brain, opiates are concentrated in basal ganglia, amygdala & periaqueductal gray matter  Administration, distribution & excretion Active ingredients of opiates: Morphine itself Heroin: molecules are inactive in the brain but it’s metabolites (morphine & monoacetylmorphine) are active Codeine: primary action through metabolites (main one being morphine, others include norcodeine & codeine-6-glucoronide)  Administration, distribution & excretion 2 phases of metabolism in liver (differential for diff. opioids): 1. Digestive system enzymes (CP450) 2. Metabolic interference (other enzymes) – conjugation btwn metabolite/ drug molecule & water- loving substance → metabolites excreted by kidneys Excretion of morphine Active transport mechanism from brain 10% excreted unchanged (in urine) ½ life = 2 - 4.5 hrs 90% eliminated codeine > propoxyphine Only reinforcing in non users if they experience pain (Fentanyl study on ‘cold’ pain) Out of lab data “Chipping” Addiction & “maturing out”  Fig 11-2 Text  Discrimination Readily discriminated from saline Morphine will generalize to all other mu opiates, but only partly to mixed agonists-antagonists Can discriminate between morphine & mixed agonists-antagonists Tolerance to discriminative effects in 1-3 days ( with dose)  Tolerance Tolerance Rapid tolerance to most effects Tolerance develops (& disappears) at different rates for different effects Tolerance due to: Metabolism Receptors Learning (context-dependent effects) Opiates & cross tolerance: Occurs with other opiates NOT with depressants, stimulants, or hallucinogens Partially occurs with alcohol  Withdrawal Never fatal Starts 6-12 hrs > last dose; peak 1-3 days; usually over