Addiction in the Brain - Latest Research. Gary M. Henschen, MD, LFAPA Chief Behavioral Health Officer Magellan Healthcare, Inc.

Addiction in the Brain - Latest Research Gary M. Henschen, MD, LFAPA Chief Behavioral Health Officer Magellan Healthcare, Inc.

The Neurobiology of Addiction

About the speaker Gary M. Henschen, M.D. is Chief Behavioral Health Officer for Magellan Healthcare, Inc. He has been employed by Magellan since 2001, and has been in his current position since 2008. In his current role, he directs a team that develops medical necessity criteria, new technology assessments, and clinical practice guidelines for behavioral health. He provides clinical expertise in new product development and the quality improvement program of Magellan. He oversees medical management for Magellan s behavioral health programs. Prior to joining Magellan, Dr. Henschen was Chief Medical Officer of Charter Behavioral Health Systems, LLC. He was previously in private practice for psychiatry and psychoanalysis in Greensboro, North Carolina for 15 years. Dr. Henschen is a graduate of Davidson College. He received the M.D. degree from the University of North Carolina at Chapel Hill. He completed his internship in medicine at Letterman Army Medical Center, San Francisco, and completed military service with the U.S. Army in Germany where he was flight surgeon and commander of the 536th General Dispensary. Dr. Henschen completed his residency and chief residency in psychiatry at Duke Medical Center, and completed psychoanalytic training at the UNC-Duke Psychoanalytic Institute. His research interests have included the assessment and prevention of suicide; psychiatric consultation-liaison with primary care physicians; the development of quality metrics; addressing the needs of individuals diagnosed with both serious mental illness and substance use disorders; and providing consultation to behavioral special investigation units. Dr. Henschen is licensed to practice medicine in Georgia, North Carolina, Tennessee, New Jersey, Pennsylvania and Iowa. 3 Copyright 2016 Magellan Health, Inc.

Learning objectives Upon completion of this activity, participants should be able to: Demonstrate the neurologic basis of addiction Discuss how treatment alters the neurological addictive patterns Outline the difference between tolerance and addiction Engage in discussions about the risks and benefits of medication-assisted treatment for opiate use disorder 5 Copyright 2016 Magellan Health, Inc.

Slippery slope to addiction Over-prescribing Pharmaceutical marketing Pain as a symptom, not a disease Little consideration for patient's substance use history, assessing for risk of addiction No consensus about who should receive how much opioid and for how long Unknowingly risking addiction Opioids suppress pain Painkillers can create a euphoric, relaxed sensation Can provide a release from stress Significant adverse side effects, overdose deaths Improper use to abuse 2 million Americans met the criteria for an opioid use disorder Taking someone else s medication to self-medicate Taking opioids in a way other than prescribed Taking medication to get high 7 Copyright 2016 Magellan Health, Inc.

The impact of prescription drug abuse Prescription drug abuse has become a public health crisis, and appropriate interventions to prevent addiction are crucial. Prescription and nonprescription opioid users of all ages can quickly become addicted. 2015 CDC. National Vital Statistics System mortality data. http://www.cdc.gov/nchs/deaths.htm(2013) SAMHSA, Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD: SAMHSA 8 Copyright 2016 Magellan Health, Inc.

How does this problem occur in the brain? Graphics courtesy of Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services

The central nervous system Comprises brain and spinal cord Brain is a functional unit Comprises billions of nerve cells that communicate with each other They use electrical and chemical signals 10 Copyright 2016 Magellan Health, Inc.

Brain regions and neuronal pathways Parts of the brain govern specific functions: sensory-blue motor-orange visual cortex-yellow cerebellum-pink hippocampus-green reward pathway-orange thalamus-magenta 11 Copyright 2016 Magellan Health, Inc.

Pathway for sensation of pain and reaction to pain When the finger is injured nerve endings in finger: sense injury send impulses along spinal cord neurons in spinal cord connect to thalamus, part of mid-brain information organized, sent to sensory cortex directs motor cortex to send information back to thalamus thalamus organizes information sends information down spinal cord motor neurons react to pain 12 Copyright 2016 Magellan Health, Inc.

Impulse flow Information flow is electrical and chemical Impulse flows down axon toward terminal-connects to dendrite of adjacent neuron Passes on chemical information Synapses can occur between terminal, soma, or axon 14 Copyright 2016 Magellan Health, Inc.

The synapse & synaptic neurotransmission Electrical impulse arrives at terminal Triggers vesicles containing neurotransmitter Neurotransmitter binds with specific proteins called receptors 15 Copyright 2016 Magellan Health, Inc.

Dopamine neurotransmission & modulation by endogenous opiates Vesicle fuses with membrane releases dopamine Dopamine molecules bind to dopamine receptor After binding-removed by uptake pumps Neighboring neurons that release neuromodulators Endorphins-bind to opiate receptors Endorphins destroyed by enzymes 16 Copyright 2016 Magellan Health, Inc.

The reward pathway and addiction

Natural rewards: Allow organism to feel pleasure when eating, drinking, procreating & being nurtured Food Water Sex Nurturing There is a brain pathway responsible for rewarding behaviors 18 Copyright 2016 Magellan Health, Inc.

The reward pathway The reward pathway ventral tegmental area nucleus accumbens prefrontal cortex VTA sends information to prefrontal cortex via neurons These neurons contain DOPAMINE Released in prefrontal cortex & nucleus accumbens Pathway activated by rewarding stimulus 19 Copyright 2016 Magellan Health, Inc.

Activation of reward pathway by an electrical stimulus Brain of rats is studied Electrode placed in nucleus accumbens Rat presses lever to receive small electrical stimulus Feels pleasurable Does not press lever when electrode placed in other areas DOPAMINE released If dopamine blocked-no pleasure 20 Copyright 2016 Magellan Health, Inc.

Addiction A state in which an organism engages in a compulsive behavior The behavior is reinforcing (rewarding or pleasurable) Loss of control in limiting intake 21 Copyright 2016 Magellan Health, Inc.

Craving Reward pathway even more important in creating craving Craving may be more important than the reward itself Clear that addiction is a brain disease Two examples of drugs that are addictive and how they affect their cellular targets in the brain and the reward pathway 22 Copyright 2016 Magellan Health, Inc.

The action of opiates: morphine, heroin, oxycontin, hydrocodone

Opiate binding sites within brain and spinal cord Heroin converted to morphine by enzymes in the brain Morphine binds to opiate receptors REWARD PATHWAY Cerebral cortex VTA Nucleus accumbens PAIN PATHWAY Thalamus Brainstem Spinal cord 24 Copyright 2016 Magellan Health, Inc.

Synapse in nucleus accumbens Opiates bind to opiate receptors Increase release of dopamine 3 types of neurons participate releases dopamine adjacent neuron with different neurotranmitter (GABA) post-synaptic cell-contains dopamine receptors Sends signal to dopamine terminalreleases more dopamine 26 Copyright 2016 Magellan Health, Inc.

Rats self-administer heroin in experiments Rat presses a bar to receive heroin Heroin injected into nucleus accumbens Creates pleasure - rat presses bar repeatedly to get heroin and pleasure Heroin is positively reinforcing If needle placed elsewhere in brain - no pleasure, no pressing the bar Dopamine is released in reward pathway More dopamine in synaptic space - dopamine-dependent neurotransmission augmented Reward pathway activated 27 Copyright 2016 Magellan Health, Inc.

Tolerance A state in which an organism no longer responds to a drug A higher dose is required to achieve the same effect With heroin or morphine - tolerance to analgesia develops rapidly Develops at level of the cellular targets Morphine binds to opiate receptors - triggers inhibition of adenyl cyclase - maintains firing of impulses Enzyme adapts quickly, so morphine no longer causes changes in cell firing 28 Copyright 2016 Magellan Health, Inc.

Dependence A state in which an organism functions normally only in the presence of a drug Manifested as a physical disturbance when the drug is removed Neurons adapt to repeated drug exposure, function normally only in presence of the drug When drug withdrawn: withdrawal syndrome 30 Copyright 2016 Magellan Health, Inc.

Brain regions mediating morphine dependence Specific areas of the brain separate from reward pathway Thalamus Brain stem Withdrawal symptoms occur when opiate receptors in these areas are deprived of morphine 31 Copyright 2016 Magellan Health, Inc.

Addiction vs. dependence Possible to be dependent on morphine without being addicted Especially true of patients with cancer or chronic pain Addiction = compulsive use 32 Copyright 2016 Magellan Health, Inc.

The action of cocaine

Snorting vs. smoking cocaine: Different liabilities Smoking freebased cocaine gets it to the brain more quickly than snorting Route more direct to the brain Time between taking the drug and positive reinforcement, rewarding effects can determine likelihood of abuse 34 Copyright 2016 Magellan Health, Inc.

Localization of cocaine binding sites Cocaine binds to sites in specific areas VTA Nucleus accumbens Caudate nucleus Binds especially in the reward areas Binding in caudate nucleus explains stereotypical behaviors Pacing Nail-biting Scratching 35 Copyright 2016 Magellan Health, Inc.

The action of cocaine: Dopamine binding Cocaine binds in sites rich in dopamine Dopamine released into synaptic space Binds to dopamine receptors-then taken back up by pumps back into terminal Cocaine binds to uptake pumps - prevents reuptake of dopamine Dopamine builds up 36 Copyright 2016 Magellan Health, Inc.

Cocaine dependence: Activation of reward pathway Cocaine binds within reward pathway VTA & nucleus accumbens Increased impulses to activate reward pathway Pathway activated in absence of cocaine craving! With repeated use-body relies on cocaine to maintain rewarding feelings No longer able to feel natural rewards In absence of cocaine-anhedonia, depression 37 Copyright 2016 Magellan Health, Inc.

Rats self-administer cocaine in experiments Increased dopamine in synapses of reward pathway in rats Rats press a bar to receive injections of cocaine into reward pathway If needle not in reward pathway, will not press bar 38 Copyright 2016 Magellan Health, Inc.

Bibliography Goldstein RZ, Volkow ND: Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat Rev Neurosci 12:652-669, 2011 Koob GF: Allostatic view of motivation: implications for psychopathology in Motivational Factors in the Etiology of Drug Abuse. Edited by Bevins RA, Bardo MT. Lincoln, University of Nebraska Press, 2004, pp 1-18 Koob GF, LeMoal M: Drug addiction, dysregulation of reward, and allostasis. Neuropsycopharmacology 24: 97-129, 2001 Koob GF, LeMoal M: Neurobiology of Addiction. London, Academic Press, 2006 Drugs, Brain and Behavior: The Science of Addiction. National Institute on Drug Abuse. Washington, 2014. 40 Copyright 2016 Magellan Health, Inc.

Questions and discussion