The Neurobiology of Street Drugs. Joe Gilboy PA-C Hoag Hospital Emergency Department Irvine, CA. Neuroplasticity. Question #1

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1 The Neurobiology of Street Drugs Joe Gilboy PA-C Hoag Hospital Emergency Department Irvine, CA Question #1 Neuroplasticity is the new field of neurobiology that is based upon which of the following : 1. Ability of the brain to change structure and function 2. Based on input from repeated behaviors, emotions, and thoughts 3. The brain can change at any age 4. Brain plasticity is a two-way street; it is just as easy to generate negative changes as it is positive ones 5. All the above Neuroplasticity

pathway in the brain? 1. Acetycholine 2. Norepinephrine 3.

2 Lets go back to school and learn some neurobiology 101 Question #2 Which neurochemical is the primary one in the pleasure reward pathway in the brain? 1. Acetycholine 2. Norepinephrine 3. Dopamine 4. Serotonin Presynaptic Cell Synaptic area Postsynaptic Cell

3 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 The Limbic System is Prehistoric

Caudate Nucleus Regulation of movement Respiratory center Remember these

Dopamine Release % of Basal Release 1100 1000 900 800 700 600 500 400

DA DOPAC HVA 0 1 2 3 4 5 hr Nicotine 0 1 2 3 hr Time After Drug

0 250 200 150 100 0 Accumbens Cocaine DA DOPAC HVA 0 1 2 3 4 5 hr

4 Caudate Nucleus Regulation of movement Respiratory center Remember these drugs are working at a prehistoric wiring level Effects of Drugs on Dopamine Release % of Basal Release % of Basal Release Accumbens Amphetamine DA DOPAC HVA hr Nicotine hr Time After Drug Accumbens Caudate % of Basal Release % of Basal Release Accumbens Cocaine DA DOPAC HVA hr Accumbens Morphine Dose 0.5 mg/kg 1.0 mg/kg 2.5mg/kg 10 mg/kg hr Time After Drug

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

5 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 Question#3 Which receptor sites do opiates work at? 1. Dopamine 2. Acetycholine 3. Mu 4. Serotonin 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 1 st Line Subutex (buprenorphine) 2 nd

6 Memory Movement Respiration Nucleus Accumbens Opiate Binding Sites End result stimulation of the reward system Treatment for Heroin Patients 1 st Line Subutex (buprenorphine) 2 nd 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

Question #4 Which of the following chemicals in marijuana

7 Question #4 Which of the following chemicals in marijuana has been shown to help with seizures? 1. THC (Tetrahydrocannabinol) 2. THCA (Tetrahydrocannabinolic Acid) 3. CBC (Cannabichromene) 4. CBD (Cannabidiol) CB1 Receptor Distribution and Functional Areas High density in brain areas concerned with memory, cognition, motor coordination and reward

MOTOR TASK Bilateral Finger Tapping Pre-Drug 15 min

8 MOTOR TASK Bilateral Finger Tapping Pre-Drug 15 min Post-Drug 35 min Post-Drug 0.5 mg 1.0 mg 3.0 mg EFFECTS OF THC ON ACTIVITY WITHIN NUCLEUS ACCUMBENS Subjects were injected with 0.5, 1, or 3 mg of THC. cannabidiol (CBD) - the major non-psychoactive ingredient in marijuana Useful in seizures especially in children

9 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

Meth? 1. Creatine monohydrate 2. Glutamate 3. Epinephrine 4.

10 What s the difference?? Question #5 What chemical has been shown to breakdown dopamine receptor sites in rats when they were exposed to Meth? 1. Creatine monohydrate 2. Glutamate 3. Epinephrine 4. Acetycholine Meth camp S Dopamine receptor site (Glutamate) breaks down receptor site Ann N Y Acad Sci Oct;1139: doi: /annals Methamphetamine changes NMDA and AMPA glutamate receptor subunit levels in the rat striatum and frontal cortex.

11 Nucleus accumbens Methamphetamines stimulates dopamine receptor sites Opiate in the receptor Nucleus sites accumbens End result stimulation of the reward system Methamphetamine crystals

12 Typical bag of crystal $40-60$ 10 Months 7 months 9 Months 1 year Thought MRI of a Methamphetamine Addict Emotions Memory

13 Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence 3 0 Normal Control METH Abuser (1 month detox) ml/gm METH Abuser (24 months detox) Source: Volkow, ND et al., Journal of Neuroscience 21, , 9418, Want to go to a Club?

14 Ecstasy MDMA E Doves Merck Company 1914 bring out peoples true feelings in a peaceful open manner NICE IDEA VERY BAD DRUG 1985 BECAME POPULAR IN EUROPEAN DANCE CLUBS Easily detected in urine and blood but not done routinely Question #6 Which neurotransmitter is primary affected by the use of Ecstasy? 1. Dopamine 2. Serotonin 3. Norepinephrine 4. Acetycholine In the 1970 s was used in psychotherapy and marriage counseling Called empathy 70 s Started off in Texas bars Ecstasy Parties Works by increasing serotonin levels Serotonin depletion after usage leading to depression Treatment=SSRIs

15 Side Effects: jaw muscle spasm, elevated temp with sweating Ecstasy users risk getting Parkinson s Disease later in life. There is effect on the dopamine transport protein

GHB/Liquid Ecstasy salty water, liquid x The New

dose Kits range from $30-$50 Powder and Liquid

18 GHB/Liquid Ecstasy salty water, liquid x The New Date Rape Drug clear liquid in 1960 s as a surgical anesthetic body builder in 1980 s GHB is a psychedelic sleep-inducer Cost 2-5$ per dose Kits range from $30-$50 Powder and Liquid GHB Onset is usually minutes with 1-4 hours of duration

GABA GHB GABA Receptor Site GHB sits on GABA sites quickly broken down in 2 hours with

19 Question #7 GHB works at which of the following receptor sites? 1. Dopamine 2. Serotonin 3. Acetylcholine 4. GABA GHB GABA Receptor Site GHB sits on GABA sites quickly broken down in 2 hours with Dawn Effect leading to possible seizures GHB GHB Quickly on board quickly metabolized to CO2 and H2O will not show up on drug screen 4-5 hours after ingestion

Kyle Hagman The worst drug crisis in American history Death rates now rival those

than 27,000/year How bad is the opiate problem?

20 Kyle Hagman 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 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, with almost 40 percent more deaths from overdoses than car crashes. In all, 29,230 people died in car accidents in 2014, while 47,055 died from a drug overdose.

21 Chasing Heroin PBS Frontline Special Complexity to a level nobody understands Lets all agree what we have been doing doesn t work time to look for a new way

All the above Addiction A state in which an organism engages in a compulsive behavior Behavior

22 Question #8 Which of the following is a contributor to the neurobiology of addiction? 1. Epigenetics 2. Environment 3. Mu receptors 4. Genetic makers 5. All the above Addiction A state in which an organism engages in a compulsive behavior Behavior reinforcing=rewarding or pleasurable Loss of control in limiting intake Why?? Genetics or environment or both?? Neuroplasticity?? Here s a bright idea!!

23 ?? Epigenetics Mu receptors Addiction vs dependence Environment Neuroplasticity

24 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. Question #9 Which of the following drugs has been shown to help with depression by possibly rewiring the neural network? 1. Paxil 2. Lithium 3. Seroquel 4. Ketamine

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

25 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) 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 Rat Park 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.

26 The researchers built a rat colony (Rat Park) which was 200 times the size of a normal laboratory cage Housed between rats of both sexes.

Question #10 In the world of neurobiology and addiction to street drugs how many co-factors are present?? 1. 1 factor 2. 2 factors 3. 3 factors 4. 4 factors 5.

28 Question #10 In the world of neurobiology and addiction to street drugs how many co-factors are present?? 1. 1 factor 2. 2 factors 3. 3 factors 4. 4 factors 5. Multiple and infinite 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. Ability of the brain to change structure and function based on input from repeated behaviors, emotions, and thoughts 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.

ones Neuroplasticity Dare to Think Maybe it s the

29 Brain plasticity is a two-way street; it is just as easy to generate negative changes as it is positive ones Neuroplasticity Dare to Think Maybe it s the cage the patient is in along with genetics and neuroplasticity

Understanding Addiction and Its Impact on the Brain. SDSMA Webinar Matthew Stanley, DO

Understanding Addiction and Its Impact on the Brain SDSMA Webinar Matthew Stanley, DO Estimated Economic Cost to Society Due to Substance Abuse and Addiction: Illegal drugs: Alcohol: Tobacco: $181 billion/year