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PSYC62H3 (139)
Lecture 8


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University of Toronto Scarborough
Suzanne Erb

PSYC62: LECTURE 8: THE OPIATES (NARCOTICS)  Used to relieve pain and continue to serve as potent pain relievers  Can produce profound dependence  Opium is derived from poppy plant  When petal falls off plant, what’s left is a pod and when it is scored with a knife, it excretes a milky substance and when dried forms a gummy substance – opium  Contains alkaloids including morphine  Morphine is main psychoactive component  Heroin – produced by modifying morphine  Methadone and oxycodone are synthetic opiates Schedule of Control  Natural opiates and synthetic opiates are schedule 2 drugs  High abuse liability, but do have approved medical usages  Heroin is a schedule 1 drug = exception o No approved medicinal uses  Codeine has significant abuse liability  Tylenol 3 is a schedule 3 drug – more available by prescription than methadone and morphine? Table 10.1  Morphine is prototype opiate analgesic given standard value of 1 and other opiates listed are compared to morphine  Heroin is 2x more potent than morphine  Codeine is less potent than morphine  Phentanyl is 100x more potent than morphine and 50x more potent than heroin o Has approved medicinal purposes  Possibility that addiction will develop  Those who use drugs medicinally do go up to developing dependence  Treatment is as brief as possible and less potent opiates used  When pain is severe and chronic enough like terminal cancer patient, tolerance will develop and higher and higher doses will develop o High doses of morphine may not be sufficient  Heroin is prescribed in the U.K for pain relief in terminal patients  Prescription for heroin in north America was never approved o Debate Should heroin be prescribed to terminally ill?  Over 15 year period of time, there was an increase in using opiate as a prescribed drug for non- medicinal/illicit drugs  Mostly oxycontin use  What if heroin was made more freely available? Would we see more abuse of the drugs? Argument for:  Heroin – semisynthetic opiate gets converted to morphine right after getting across blood brain barrier, but heroin does this rapidly and therefore it is a way more potent drug o Not a compelling argument  Terminal cancer patients become thin and become unable to tolerate frequent and large volumes to tolerate pain Pharmacology  Amphetamines and cocaine activate all of the monoamine systems, while opiates only activate certain ones  Naturally occurring opiate like molecules in the brain, endorphins stimulate opiate receptors  Presence of receptors must mean there are naturally occurring molecules in brain  Other drugs act by triggering activity of endorphins Slide 8  Person may sustain a severe injury but not feel pain for a period of time, reducing the pain naturally via endorphins  Runner’s high – endorphins released after extensive exercise to produce euphoric effects in brain naturally o Mid-brain dopamine system mediate rewarding effects  Involved in pain and indirectly reward systems at midbrain are opiates Opioid receptors  VTA and nucleus accumbens – reward system  Locus coeruleus – brain stem with norepinephrine cell bodies o Regulates stress response o Managing anxiety  Activation of opiate receptors act to inhibit norepinephrine and reduce stress responses Slide 10  Figure in diff chapter  More +++ signs, greater potency of activity at that subclass of receptors  Exogenous agonists (drugs taken) activate mu receptors only  Blocking kappa receptors can contribute to managing opiate dependence and addiction  Mixed agonist-antagonist have an overall antagonistic effect  Buprenorphine is efficient in treating opiate addiction o Promising and recent therapy  Antagonists are potent at mu opiod receptors not a surprise  Opioids can increase activity in dopamine system by inhibiting norepinephrine systems Slide 12 – opiates are depressants of CNS, but can increase activity of dopamine via disinhibition Opiate Rs in dopamine pathway  3 neighbouring neurons all converging on one synapse  Terminal ending of dopamine containing neuron from VTA releasing dopamine  Adjacent neuron has gaba  Other neuron contains gaba – major inhibitory NT  Both synapsing with terminal of another neuron with dopamine receptors where to act  Receptors of dopamine on synapse  receptors on gaba cells, will send a signal to dopamine containing neuron to stop releasing more dopamine under normal situaitons  When opiates bind to receptors and inhibit gaba, signal not sent and dopamine released  When dopamine neurons disinhibited, increased availability of dopamine binding occurs  Opiates dishinbit dopamine neurons  Opiates inhibit gaba and disinhibit dopamine Historical Perspective  Sleep inducing effects of opium known for thousands of years  Simirians 6000yrs ago, medical purposes by ancient greeks and romans  Not a problem in Europe or north America in beginning of nineteenth century  Morphine is more x more potent than opium  Development of hyperdermic syringe  Taking morphine orally is associated with higher abuse liability than chewing opium or taking opium orally, injecting morphine extreme abuse liability  Hyperdermic syringe made injecting morphine a common practice Harrison Act  Opiates were regulated drugs  Heroin could still be prescribed, but was banned later  Number of individuals seeking treatment and emergency cases  Naida – major government body overseeing drug works o More than 1000 deaths a year due to opiates Opiates: medicinal uses  Analgesia o Primary medical benefit o Block sensation of pain to be transmitted to brain from spinal cord o Reduces negative feelings connected to pain o To some condition, person will continue to feel pain through actions of drugs in brain- reward pathway – increase dopamine secretion o Don’t completely numb individual to pain o Able to manage it by responding to it in a more positive way  Cough suppression o Opiates act to slow activity of coughing located in medulla of brain stem o Codeine used to suppress coughs o High level of efficacy o Used to be available in cough syrups over the counter o Not only available over prescription o Mexdretafin found in cough suppressants in place of codeine  Have selective cough suppressant effects, but not associated with same abuse potentional as codeine and other opiates  Preferred opiate in cough syrup preparations  Heroin addiction o Opiates used to treat opiate addiction o Methadone most common o Mix
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