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Neuroplasticity and Street Drug Addiction

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Neuroplasticity and Street Drug Addiction The Neurobiology of Street Drugs and Addiction Joe Gilboy PA-C Hoag Hospital Emergency Department Irvine and Newport Beach, CA Your brain is a complex neural network “What fires together wires together” Neuroplasticity I want you to leave with more questions and less answers Let's go back to school and learn some neurobiology Presynaptic Cell Synaptic area Postsynaptic Cell Normal day Dopamine Uptake pumps Dopamine receptor sites Reward System Dopamine (Reward Chemical) Limbic System Ventral tegmental area Remember this area is your hard drive level Caudate Nucleus Regulation of movement Respiratory center Remember these drugs are working at a prehistoric wiring level Effects of Drugs on Dopamine Release Amphetamine Cocaine 1100 Accumbens 400 Accumbens 1000 900 DA 800 300 DOPAC DA HVA 700 DOPAC 600 HVA 200 500 400 300 100 200 100 % of Basal Release % of Basal Release 0 0 0 1 2 3 4 5 hr 0 1 2 3 4 5 hr Morphine 250 Nicotine 250 Accumbens Dose 200 Accumbens 200 0.5 mg/kg Caudate 1.0 mg/kg 150 2.5mg/kg 150 10 mg/kg 100 100 0 % of Basal Release 0 % of Basal Release 0 1 2 3 hr 0 1 2 3 4 5 hr Time After Drug Time After Drug Methamphetamines Stimulation of dopamine in the limbic system Can be snorted, smoked, or injected Highly addictive and tissue tolerance strong cravings “Tweakers” are highly agitated and paranoid Amphetamine Methamphetamine What’s the difference?? Generation Adderall A version of this article appears in print on Oct. 15, 2016, New York Times Sunday Magazine Psychosis with Methylphenidate or Amphetamine in Patients with ADHD March 21, 2019 N Engl J Med 2019; 380:1128-1138 DOI: 10.1056/NEJMoa1813751 https://www.dea.gov/press-releases/2019/02/14/whitinsville-woman-faces-20- years-prison-adderall-distribution Meth cAMP S Dopamine receptor site breaks down after chronic use Mitochondrial breakdown because of glutamate Ann N Y Acad Sci. 2008 Oct;1139:232-41. doi: 10.1196/annals.1432.028. Methamphetamine changes NMDA and AMPA glutamate receptor subunit levels in the rat striatum and frontal cortex. MRI of a Methamphetamine Addict Thought Emotions Memory Nucleus accumbens Methamphetamines stimulates dopamine receptor sitesOpiate in the receptor Nucleus sites accumbens End result stimulation of the reward system Narcotics/Opiates Heroin,oxycodone, Vicodin It was brought to China by Arab traders in the eighth century The British, East India Company became a chief supplier and promoter of opium for the Chinese market In England heroin is mixed with alcohol cocktail to terminally ill cancer patients Heroin/opiate Mu receptors No competition more stimulation of dopamine receptor sites (Mu can grow when stimulated) Memory Movement Respiration Nucleus Accumbens Opiate Binding Sites End result stimulation of the reward system Treatment for Heroin Patients 1st Line Subutex (buprenorphine) 2nd Line Suboxone (buprenorphine+ naloxone) Can use methadone prefer to give at methadone clinics where it is dispensed as a liquid to prevent abuse Chasing Heroin PBS Frontline Special The worst drug crisis in American history • Death rates now rival those of AIDS during the 1990s • Overdoses from heroin and other opioids now kill more than 27,000/year What started the fire • Pain 5th vital sign • Originated in the VA hospital system late 1990s and became a Joint Commission standard in 2001. • Purdue Pharmaceutical • OxyContin, introduced in 1995, was Purdue Pharma’s breakthrough palliative for chronic pain How bad is the opiate problem?? • In 1999, there were more than twice as many motor vehicle deaths as fatal drug overdoses. By 2014, those numbers had flipped Chasing Heroin PBS Frontline Special Kim Jadda’s vaccine works a bit like a sponge it sucks up the heroin and prevents it from reaching the brain the vaccine prevents the drug from reaching the brain at all. Narcan in a vaccine One way to look at it is that addiction is the compulsive repetition of getting “a reward” despite life damaging consequences Do they work? What is the standard rehab success rate? There is no standard definition of rehab Many base their success rates on unreliable metrics: • Completion of the program • Sobriety rates immediately after treatment • Client interviews • Internal studies • Dr. Lance Dodes spent more than 20 years studying and treating addiction. His latest book: • The Sober Truth: Debunking the Bad Science Behind 12-Step Programs and the Rehab Industry. AA Success Rate 5-10% • And to its credit • AA describes itself as a “brotherhood rather than a treatment” Drug & Alcohol Rehabilitation Clinics industry trends (2014-2019) Average industry growth 2014–2019: 4.6% 700 Billion: Nation annually in costs related to crime, lost work productivity and health care 3x: The amount the business of recover increased in the last 25 years 14,000: The amount of addiction treatment facilities $35 billion: annual revenue generated by the addiction treatment industry Lyft -- $15.1 billion Source: Substance Abuse and Mental Health Services Administration Generally, the price tag for rehab is: •Outpatient: $3,000 – $10,000 for 90 days •Inpatient: $5,000 – $20,000 for 30 days •Luxury: $30,000 – $100,000 for 30 days Sober living home average about $1,500-2,500 per month. Missing a payment can result in expulsion from the home. Source: Substance Abuse and Mental Health Agency (SAMHSA) In the end rehab facilities don’t work $$expensive$$ www.thebusinessofrecovery.com Here’s a bright idea!! Neuroplasticity Neuroplasticity the potential that the brain has to reorganize by creating new neural pathways to adapt, as it needs Changes being made in the brain as the brain's way of tuning itself to meet your needs Formerly held belief that the adult brain was pretty much a physiologically static organ hard-wired after critical developmental periods in childhood your brain is much more plastic during the early years and capacity declines with age WRONG: plasticity happens all throughout your life Neuroplasticity • Ability of the brain to change structure and function based on input from repeated behaviors, emotions, and thoughts “What fires together wires together” In Donald Hebb's (1940s) memorable words: What fires together wires together — neurons that activate each other become more strongly connected — through adjustments (increased efficiency) in their synapses. Neuroplasticity is the brain's natural starting point for all learning processes — processes that might include not only addiction but also recovery Shackleton-Jones, Nick (2019-05-03). How people learn : designing effective training to improve employee performance. London, United Kingdom. ISBN 9780749484712. OCLC 1098213554 O'Brien CP. Neuroplasticity in addictive disorders. Dialogues Clin Neurosci. 2009;11(3):350–353. Shaffer J. Neuroplasticity and Clinical Practice: Building Brain Power for Health. Front Psychol. 2016;7:1118. Published 2016 Jul 26. doi:10.3389/fpsyg.2016.01118 Brain plasticity is a two-way street; it is just as easy to generate negative changes as it is positive ones What fires together wires together Why do people become addicts?? Epigenetics Mu receptors Addiction vs dependence Environment Neuroplasticity • Recent studies provides strong evidence that stimulant addiction may result in large part from underlying, inherited genetic abnormalities in brain structure that encourage impulsive behavior and impaired control. • Ersche KD et al. Abnormal brain structure implicated in stimulant drug addiction. Science 2012 Feb 3; 335:601. Complexity to a level nobody understands Lets all agree what we have been doing doesn’t work time to look for a new way Neuroplasticity • Ketamine improves mood disorders within hours not weeks • Repairing damage connections • SSRIs may be wrong Depression may be the result os stress-induced damage to brain cells that control mood The use may lead to newer drugs • National Institute of Mental Health (NIMH) Neurons with budding after Ketamine About 99 percent of genes in humans have counterparts in the mouse 80%have identical, one-to-one counterparts What fires together wires together LSD and Anxiety in Cancer patients • Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer • J Psychopharmacol. 2020 Feb;34(2):155-166. doi: 10.1177/0269881119897615. Epub 2020 Jan 9 LSD and nicotine addiction • Johnson, M.W., Griffiths, R.R. Potential Therapeutic Effects of Psilocybin Neurotherapeutics 14, 734–740 (2017) • South America • Ibogaine is converted into a noribogaine • targets the areas of the brain affected by drug-seeking and addictive behaviors • Noribogaine “rewires” these areas, allowing the brain to restructure itself to a state similar to before addiction was triggered. • Belgers, M., Leenaars, M., Homberg, J. et al. Ibogaine and addiction in the animal model, a systematic review and meta- analysis. Transl Psychiatry 6, e826 (2016). • Rat Park (environment) • was a study into drug addiction conducted in the late 1970s (published in 1980) by Canadian psychologist Bruce K. Alexander and his colleagues at Simon Fraser University in British Columbia, Canada • The researchers built a rat colony • (Rat Park) which was 200 times the size of a normal laboratory cage • Housed between 16 – 20 rats of both sexes. His neural connections are healthy, and his wiring is working well What fires together wires together So the opposite of addiction is not sobriety It is human connection Neuroscientist Marc Lewis argues that addiction – or dependence, is the result of "deep learning", probably triggered by stress or alienation. It can duly be unlearned by forging stronger synaptic pathways via better habits. What fires together wires together The Biology of Desire: Why Addiction Is Not a Disease by Professor Marc Lewis Nearly fifteen years ago, Portugal had one of the worst drug problems in Europe 1 percent of the population addicted to heroin They had tried a drug war, and the problem just kept getting worse So they decided to do something radically different.
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