Substance Use Disorder Lecture Notes PDF

12/3/24 Substance use and addiction Lecture 40 NRS301...

12/3/24 Substance use and addiction Lecture 40 NRS301 December 4th, 2024 1 Overarching Questions: 1. What is substance use (SUD)? How is it different from addiction? What are the symptoms of SUD? Who is at risk? 2. How do drugs of abuse change the brain? What circuits are affected? How do these changes perpetuate SUD and withdrawal symptoms? 3. How can we help people with SUD? Are there treatments? Can an individual and the brain actually recover? 2 Substance use disorder vs. addiction substanceuse is a spectrum Substance use disorder (SUD) – inability to control the consumption or use of legal or illegal substances Alcohol Prescription medications Illicit substances Individuals compulsively use but still have control of their own lives justaPathetroutine Addiction – most severe form of SUD Compulsive/habitual use Dependent Lives have spiraled out of control 3 1  12/3/24 Symptoms of SUD Set forth by the DSM V – diagnostic tool for of habituationthe substance neuropsychiatric conditions Mild SUD: 2-3 symptoms Moderate: 4-5 symptoms Severe: 6+ Phffling f rom addiction 19thpening Addiction is not part of the DSM V. because itisa spectrummild Sun 4 be canalso addiction Prevalence of SUD Approximately 16.7% of Americans aged 12 or over have experienced substance use disorder in their lifetimes. Average across all types of substance use. 10.2% Alcohol use 9.7% Prescription drug use 24.1% Illicit drug use In many cases SUD and addiction can be lifelong 30% of alcoholics 10% for other drugs riskdepends 5 O ta9 e olvsdrugs Problematic Mortality rates associated with SUD importanttoidentifysub Here we are only considering drug use, but the same trends are seen for alcohol-related deaths. For most cases, steady & progressive increase in overdoses. Exception is Fentanyl and methamphetamine Cocaine to a lesser extent 6 2  12/3/24 Who is at risk? A YoungindividualsmoreatriskforSUD signifists SUD and addiction begins to climb in teen goesalongwthedevelopmentofthebrain years. Peaks in mid-late 20s. Coincides with heightened sensitivity to reward (teens) & maturation of the prefrontal cortex (adulthood; ~25) 7 Who is at risk? Sexdifferences stigmaforfemales isworseespecially ifpreggoor Highera > Prevalence > History of substantial > Transition to addiction >Prescription pill abuse aparent use (binges) > Engage in risky social > age behavior > Heroin abuse > co-morbid psychiatric conditions > engage in violence or criminal activity > stigma, especially if parent or pregnant > number of deaths > Barrier to treatment > employed 8 Social Stigma around SUD duetothestigmatheyfeelisolatedand Individuals with SUD or addiction are often seen as aloneanddonotwantto seekhelp dueto it Lazy Powerless Hopeless Lost Cause Untrustworthy Social stigma can keep individuals from searching for treatment or support & increase the likelihood that someone will drop out of treatment 9 3  12/3/24 noteveryone w SUD is a bad person “My biggest struggle with my addiction is knowing that the world thinks bad of me simply for having this illness. I recently watched Suicide Squad […] and cried when the father of one of the characters was an addict but also a good person who loved his daughter. I really struggle to find characters in media who are struggling with addiction who are portrayed in more than one depiction (that depiction being evil, criminal, wanting to hurt people etc.)[…] ” – mollyplop r/addiction 10 Overarching Questions: whichstatement istrue 1. What is substance use (SUD)? How is it different from addiction? What are the symptoms of SUD? Who is at risk? it is a normalbehavior youngppl 2. How do drugs of abuse change the brain? What circuits are affected? How do these changes perpetuate SUD and withdrawal symptoms? 3. How can we help people with SUD? Are there treatments? Can an individual and the brain actually recover? 11 Rewards come in different forms EY Most of our behavior is driven by CBGE bEd reward. Food is rewarding. Fat & sugar especially Drives food selection Social interactions are food rewarding. Drives selection of social partners Passing that hard OChem exam is rewarding. incentive honey hunteering Reinforces studying methods 12 4  12/3/24 819 Reward circuit in the brain rewardcircuitevolvedforsurvival foods Evolved to help guide our behavior to favorable outcomes. Food is a potent activator of the reward circuit. highinenergy good wantto remember Foods high in fat & sugar This is adaptive! It helps our survival. Yatsidreatheteras Consume Learning Relative caloric value Guides behavior to seek out those foods in future Substances like alcohol or drugs of abuse hijack this system. Much more potent. 13 Reward circuit in the brain Reward circuit is not just dopamine! VTA – primary source of dopamine to Yimitew reward system NAc – responds to environmental cues to produce craving & seeking Stm – coordinates with the motor system to engage in seeking & taking behaviors of the drugs Amg – emotion, mood, affect involved w m ore withdrawal PFC – Regulates activity in projection regions Stopaowncontrol Hpc – formation of memories ftp.ie atjnea 14 Neurobiological basis of addiction Medsa ae Binge/Intoxication activation of the reward circuit Basal ganglia (Striatum/Putamen) Ventral tegmental area Nucleus accumbens ing PEEWEE Linking cues with the rewarding, pleasurable feeling of substance use Classical conditioning heatingYni9 Environmental cues (conditioned stimulus) Substance (unconditioned stimulus) Feeling of pleasure/euphoria (conditioned response) Cues gain motivational significance and cravings 15 5  12/3/24 Neurobiological basis of addiction Binge/Intoxication Neurotransmitters involved Dopamine ↑ Endogenous opioids ↑ Serotonin ↑ heletrotransmitters GABA ↑ involved Acetylcholine ↑ Effects are in striatum and contribute to use, associative learning, and euphoric/pleasurable feelings Mys d 16 Neurobiological basis of addiction likea hangoverbutworse Withdrawal/Negative affect Activation of networks that regulate emotion & anxiety Amygdala Etihad theirs Bed Nucleus of the Stria Terminalis (BSNT) Stop using and enter a hypodopaminergic state Loss of motivation Emergence of negative emotions Increased sensitivity to stress teaketness Circuits become more active Loss of coping 17 shifiission Neurobiological basis of addiction Preoccupation/Anticipation Reduced activity of prefrontal cortex tanintonahi.fi sYitnYm Increase in compulsive and impulsive behaviors Strong urges to use especially in response to stress or negative emotions Exposure to cues associated with use produce strong craving and urges to use Loss of PFC function increases the likelihood to use 18 6  12/3/24 Neurobiological basis of addiction These stages overlap and severity increases as astheygointoaddictionthecycle is a factor of duration of use. fasterandfaster There are two camps in neuroscience to describe why we transition to addiction. 1. Koob Theory – Individuals continue to use to self medicate and offset the negative effects withdrawals ymptoms 2. Robinson & Berridge Theory – Extended use is associated with heightened “wanting” (motivation) for substance Transition toreward system addiction is super is likely a sensitive mix of these theories 19 Neurobiological basis of addiction Historically, substance use disorder and addiction have been linked to dopamine – drugs of abuse directly impact dopamine but are there much m oresystemsi nvolved Virtually every neurotransmitter system is involved. Binge/Intoxication W ithdrawal/ Preoccupation/ Negative Affect Anticipation Dopamine Corticotropin-releasing Dopamine Opioid peptides factor Glutamate Serotonin Dynorphin Orexin GABA Norepinephrine Hypocretin Acetylcholine Orexin Serotonin Substance P Corticotropin-releasing Dopamine factor Serotonin Opioid peptide receptors Do not memorize – Neuropeptide Y this list is to make Endocannabinoids my point Oxytocin 20 Neurobiological basis of addiction Historically, substance use disorder and addiction have been linked to dopamine – drugs of abuse directly impact dopamine Virtually every neurotransmitter system is involved. no Hold 198 i Neurotransmitter levels increases Release probability normally a ock Sensitivity of receptors increased normally 0 Change # of receptors on synapses Shifts in # of transporters Specific fallen out 21 7  12/3/24 Effects of cocaine on dopamine transporter morereceptorsareactive Cocaine increases the intensity of dopamine signaling by blocking dopamine transporter. More dopamine stays in the synapse overtimestopmakingDATSbcdon'twantto Over time, brain will downregulate 1. Dopamine transporters (DAT) wasteenergy Fewer # of DATs on the presynaptic neuron 2. Downregulation of dopamine receptors Fewer # of receptors on the postsynaptic neuron Braintrying isthis YFGotmkeiohsfaftpiagfty.ly 22 toadapt Lecture 35: Clinical example of Homeostatic Plasticity Long-term alcoholics cannot simply stop drinking. Quitting “cold turkey” can lead to epilepsy and death in these individuals. Why? Alcohol is a depressant & alters the sensitivity to inhibitory GABA. Reduction in the number of GABAergic receptors Compensates for the depressive “inhibitory” nature of alcohol When alcohol is removed, normal GABAergic tone is significantly reduced the brain becomes overly excitable Normal withdrawal symptoms result from this as well & synapses can recover Can contribute to development of tolerance losingnewnormal 23 Need alotmore cocainetoget effectwanted Overarching Questions: 1. What is substance use (SUD)? How is it different from addiction? What are the symptoms of SUD? Who is at risk? 2. How do drugs of abuse change the brain? What circuits are affected? How do these changes perpetuate SUD and withdrawal symptoms? 3. How can we help people with SUD? Are there treatments? Can an individual and the brain actually recover? 24 8  12/3/24 Can you truly recover from SUD? Popular saying - “Once an addict, always an addict” isthsimttei.name Addiction and SUD can be a lifelong struggle For some that is the case, for others it isn’t Many Psychologists challenge this idea stating that this concept is associated with: after Shame – You forever label yourself as an addict & live with the stigma/condemnation that comes with this label Feelings of powerlessness – implies that you can never be free, addiction will always prevail no matter what you do Recovery is not a linear process and it’s not the same for everybody. infuriating thgmashvaldict 25 Relapse Relapse – return to SUD after a period of abstinence Returning to previous levels of use Fallen back into the original use pattern notietaf.ie affingean r Relapse is often associated with shame and guilt, but it is surprisingly common! Rates depend on substance partoftreatment Several triggers that can lead to relapse. 50 ofpeoplew subrelapse 26 spiralofsymptoms Triggers that lead to Relapse: Withdrawal Withdrawal symptoms build and compound on one another. Symptoms are Cognitive ahtsttiiantn'ew faynit.tn Emotional happening Physical normal together Symptoms arise as the brain and body are adjusting to the loss of the substance. Reflects homeostatic changes due to drug use Takes time for the system to “rebalance” Discomfort of withdrawal can trigger relapse 27 9  12/3/24 Treating withdrawal symptoms/syndrome Drug treatments that can lessen the burden of withdrawal: 1. Diazepam (Valium) – withdrawal from sedatives Alcohol, Benzodiazepines, other Barbiturates Treating cognitive & emotional symptoms of withdrawal 2. Clonidine/Methadone – withdrawal from opiates Heroine, morphine, prescription pain medications Treating physical symptoms of withdrawal notmanymppppmjca t.hr These drug treatments work because withdrawal symptoms are predictable and identifiable. Not the case for stimulants (Cocaine, amphetamine). Diazepam may be useful. 28 nGlanPaY'sitting'athi.MY aidbce Triggers that lead to Relapse Triggers directly affect the reward system in the brain to promote reward seeking: Stress (Cortisol) – increase dopamine in reward system Environmental Cues (People, Places, Sensory stimuli associated with use) – direct activation of nucleus accumbens Re-exposure – substances directly acts on dopamine charing 29 mayhap.gs niintfrsesetiaYiors Cognitive Behavioral Therapy/Support Groups “Attendance in an abstinence-based treatment program increases recovery rates from 41% to 80% […]” Provide social and emotional support Breaking the stigma – your story is reflected in others Cognitive behavioral therapy Skills training - Individuals learn active coping mechanisms to manage these triggers. the mitigate stressors Contingency management - overcome the rewarding nature of the drug by providing non-drug alternatives (ex. money) Relapse prevention – “reprogram” behavioral responses and expectations to environmental cues 30 10  12/3/24 The brain does recover from SUD Dopamine transporters recover, in part, after extended abstinence. Methamphetamine Similar recovery patterns across substances This takes an extended amount of time (~14 months). It is unclear if the brain will ever return to “normal” but some function is regained 31 11