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The Disease Model of Opioid Addiction. Vincent Giannetti, PhD – Pharmacy Benedict Kolber, PhD – Biological Sciences. Outline. Giannetti Chemical dependency Abuse vs dependence Evolutionary psychology of abuse Disease process of abuse Kolber Biological mechanisms of abuse.
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The Disease Model of Opioid Addiction Vincent Giannetti, PhD – Pharmacy Benedict Kolber, PhD – Biological Sciences
Outline • Giannetti • Chemical dependency • Abuse vs dependence • Evolutionary psychology of abuse • Disease process of abuse • Kolber • Biological mechanisms of abuse
Chemical Dependency Periodic or chronic intoxication produced by the repeated consumption of a drug Characteristics Compulsion to use in spite of negative consequences Tolerance and tendency to increase dose Physical and or psychological dependence Behavioral impairment
Abuse versus Dependence Abuse Behavioral impairment Continued use in spite of negative consequences Dependence Tolerance Withdrawal Loss of control Preoccupation with use to the exclusion of other activities
Evolutionary Psychology I • Old brain • Brain stem, cerebellum and limbic system • Regulates respiration, heartbeat, body temperature, muscle movement, • Mediate emotions and cravings (anger, fear, thirst, pleasure) • Imprint survival memories (noxious and pleasurable experiences) • Old brain retains addiction memories • Adapted Uppers Downers and All Arounders: Inaba and Cohen, CNS Productions Inc
Evolutionary Psychology II • New Brain • Neocortex (cerebrum and cerebral cortex) • Information processing and reasoning • New brain is late in developing • Old brain predominates in stress and crisis (automatic tendency to revert to old brain functioning) • Adapted Uppers Downers and All Arounders: Inaba and Cohen, CNS Productions Inc.
Compulsion and Drug Dependence • On/Off Switches • Satiation Centers • When repetition of an action satisfies a drive, craving is turned off. • Healthy functioning person integrates drives of the old brain with reasoning ability of new brain. • Why can’t craving stop. • Repeated administration overrides and disrupts satiety • Repeated administration disrupts communication between the two brains • Repeated administration lays down powerful primitive memories that overwhelm the new brain • Physiological basis of superego, ego and Id • Adapted Uppers Downers and All Arounders: Inaba and Cohen, CNS Productions Inc.
Continuum of Drug Abuse Experimental Social-recreational Circumstantial-situational Intensified Compulsive
The Disease Process Initiation Experimentation Social influence Escalation Preoccupation Intoxication is normalized Maintenance Social fabric of life unravels Use becomes compulsive
Etiology of Chemical Dependency Social rebellion Symptom relief Learned behavior Drive -cue-response -reinforcement Tolerance-dependency-response -reinforcement Personality traits Disease
Dopamine and AddictionMolecular Psychiatry (2004) 9, 557–569. doi:10.1038/sj.mp.4001507 Published online 6 April 2004 The involvement of dopamine in drug reinforcement is well recognized but its role in drug addiction is much less clear. Imaging studies have shown that the reinforcing effects of drugs of abuse in humans are contingent upon large and fast increases in dopamine that mimic but exceed in the intensity and duration those induced by dopamine cell firing to environmental events. In addition, imaging studies have also documented a role of dopamine in motivation, which appears to be encoded both by fast as well as smooth DA increases. Since dopamine cells fire in response to salient stimuli, the supraphysiological activation by drugs is likely to be experienced as highly salient (driving attention, arousal conditioned learning and motivation) and may also reset the thresholds required for environmental events to activate dopamine cells. Indeed, imaging studies have shown that in drug-addicted subjects, dopamine function is markedly disrupted (decreases in dopamine release and in dopamine D2 receptors in striatum) and this is associated with reduced activity of the orbitofrontal cortex (neuroanatomical region involved with salience attribution and motivation and implicated in compulsive behaviors) and the cingulate gyrus (neuroanatomical region involved with inhibitory control and attention and implicated in impulsivity). However, when addicted subjects are exposed to drug-related stimuli, these hypoactive regions become hyperactive in proportion to the expressed desire for the drug. We postulate that decreased dopamine function in addicted subjects results in decreased sensitivity to nondrug-related stimuli (including natural reinforcers) and disrupts frontal inhibition, both of which contribute to compulsive drug intake and impaired inhibitory control. These findings suggest new strategies for pharmacological and behavioral treatments, which focus on enhancing DA function and restoring brain circuits disrupted by chronic drug use to help motivate the addicted subject in activities that provide alternative sources of reinforcement, counteract conditioned responses, enhance their ability to control their drive to take drugs and interfere with their compulsive administration. Bottom line of dependency Our brains are wired to ensure that we will repeat life-sustaining activities by associating those activities with pleasure or reward. Whenever this reward circuit is activated, the brain notes that something important is happening that needs to be remembered, and teaches us to do it again and again, without thinking about it. Because drugs of abuse stimulate the same circuit, we learn to abuse drugs in the same way. When some drugs of abuse are taken, they can release 2 to 10 times the amount of dopamine that natural rewards do. In some cases, this occurs almost immediately (as when drugs are smoked or injected), and the effects can last much longer than those produced by natural rewards. The resulting effects on the brain’s pleasure circuit dwarfs those produced by naturally rewarding behaviors such as eating and sex. The effect of such a powerful reward strongly motivates people to take drugs again and again. This is why scientists sometimes say that drug abuse is something we learn to do very, very well. National Institute of Drug Abuse
Treatment Process Intervention Confrontation and leveraging Assessment Degree of impairment Dual diagnosis Treatment planning Detoxification Residential / intensive day/ counseling Aftercare Relapse prevention/ AA, NA
Neurobiology of addiction • Addiction risk in chronic pain patients • Still controversial • 1-5% of genes change with acute drug administration
Brain areas of addiction • Dopamine neurons in VTA project to ventral striatum, nucleus accumbens, amygdala, prefrontal • DA release signals reward/change in reward; acts as a reward prediction signal (learned associations); signals how much reward is wanted vs liked (incentive salience) • DA release is transferred from drug itself to learned associations and wanting • MOR activation in VTA is rewarding by inhibition of GABA neurons in the VTA which then causes DA to increase
Neurobiology of Addiction Analgesia/addiction Addiction Al-Hasani & Bruchas, 2011 Anesthesiology
The High and The Low • The feelings of “low” after the “high” are hypothesized to be simply a return to homeostasis • Aversive state of withdrawal is strengthened by repeated drug taking – i.e. people take drugs to avoid withdrawal • This theory does not explain relapse (withdrawal symptoms go away but the patient relapses) • Biology of withdrawal • Rebound excitation of noradrenergic and serotonergic systems