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Home , Acetylcholine, Neurotransmitter

Howdy! Balance: The Key to Understanding

Jeff Sandoz, PhD Troy University Acknowledgements

• Special thanks go to Dr. Fred Von Stieff for permission to use his diagram in this presentation from his book In Balance. • With gratitude for Dr. Daniel Inaba and CNS Productions Inc. for the use of the information on slides courtesy of CNS Productions, Medford Oregon via their publication Uppers, Downers, All Arounders. Outline - Neurotransmitter Balance

I. Book Brain In Balance II. Neurotransmitter System III. GABA Glutamate IV. Brain Scans & the Future Book I

IV Brain Scans & the Future III VS. II Mind Map Neurotransmitter Visual Systems I. Book

Rosetta Stone: Understand the 3 Factor Relationship among Drug Use, Craving & levels. About the Author •Board-certified Addictionologist •Over 20,000 successful detoxified patients [Evidence-Based Best Practice] •Medical Director three chemical dependency programs •Certified-American Board of Addiction Medicine •Certified-American Society of Addiction Medicine •Certified-California Society of Addiction Medicine •Chief Medical Review Officer-State of California Dr. Von Stieff •Legal expert in II. Neurotransmitter Systems Goal: Learn the rules of HOW THE BRAIN WORKS, making of how the neurotransmitters function.

Analogy: Putting together pieces of the Brain Puzzle Build a puzzle: Start on the borders & work your way in. Glutamate Endocannabinoid GABA Premise: Brain is Seeking Balance Most healthcare professionals do not understand how addiction and detoxification affect systems of patients. Dynamic State of Equilibrium Neurotransmitter Diagram

Purpose: Understand brain imbalance related to addiction – Done by viewing neurotransmitter levels of patient. 8 Neurotransmitters

Add 7 colors of the rainbow and white to enhance your of the location of each neurotransmitter. [ROY G BIV] 8 Basic Neurotransmitter Systems Visualizing this diagram helps to understand what is going on in the person’s brain. Specifically how neurochemical balance can be altered. Diagram: Placing the Neurotransmitters • Large circle represents patient’s brain.

• 8 smaller circles represent eight neurotransmitter systems. Diagram: Placing the Neurotransmitters • Resembling the chambers of a six shooter • + one more • & one in the middle. Diagram: Placing the Neurotransmitters • Resembling the face of a clock: • in the middle. Diagram: Placing the Neurotransmitters • Resembling the face of a clock: • Serotonin at 1 o’clock Diagram: Placing the Neurotransmitters • Resembling the face of a clock: • GABA between 2 and 3 o’clock Diagram: Placing the Neurotransmitters • Resembling the face of a clock: • Glutamate between 4 and 5 o’clock Diagram: Placing the Neurotransmitters

• Resembling the face of a clock: • Dopamine at 6 o’clock Diagram: Placing the Neurotransmitters • Resembling the face of a clock: • Noradrenaline between 7 and 8 o’clock Diagram: Placing the Neurotransmitters • Resembling the face of a clock: • Acetylcholine between 9 and 10 o’clock Diagram: Placing the Neurotransmitters • Resembling the face of a clock: • Endocannabinoid at 11 o’clock Visualizing the Neurotransmitter System Utilize Diagram 4 1) Genetic Deficiencies Imbalance due to Mental Illness, Trauma, Stress Visualizing the Neurotransmitter System Utilize Diagram 4 Times 1) Genetic Deficiencies Imbalance/MI/Trauma 2) Effect of Self- Medicating Drugs Visualizing the Neurotransmitter System Utilize Diagram 4 Times 1) Genetic Deficiencies Imbalance/MI/Trauma 2) Effect of Self- Medicating Drugs 3) Withdrawal & Detox Visualizing the Neurotransmitter System Utilize Diagram 4 Times 1) Genetic Deficiencies Imbalance/MI/Trauma 2) Effect of Self- Medicating Drugs 3) Withdrawal & Detox 4) Stabilization:Add Meds to Correct or Balance the System Address & Analyze Patient Neurochemical Imbalance 1 Genetic Deficiencies, Predispositions in Family -Stress/Mental Illness, Trauma Sources –Psychosocial History, Genogram, Family Drinking Survey. Helpful information with regard to genetic issues – neurotransmitter deficiencies and imbalances. Diagram 1 – Showing the Genetic Ailment • Disposition –Mental status/ emotional mood • Background – Family members DSM-V Neurotransmitter X • Cravings –Past/Present Drug Use Acetylcholine • Sketch diagram/X marks Endocannabanoid neurotransmitter Serotonin • Review notes on possible GABA neurotransmitters out of balance. Glutamate Review research on pubmed.com. Dopamine Noradrenaline Diagram 1 – Showing the Genetic Ailment

• Genetic Predispositions in Family Condition X Alcoholism Bipolar Anxiety Depression X Drug Addiction Eating Disorders PTSD Other Diagram 1 – Showing the Genetic Ailment • Example - Addiction & Depression • Drug of Choice Cocaine. Review research on pubmed.com. • Family Conditions DSM-V Parental Addiction

X Condition Neurotransmitter Alcoholism Acetylcholine Bipolar Endocannabanoid Anxiety Serotonin 5-HT Depression X 2A Schizophrenia GABA Drug Glutamate ? Addiction Dopamine Eating Disorders Noradrenaline PTSD Other Opiate Address & Analyze Patient Neurochemical Imbalance 2 Drugs/Alcohol affect Neurotransmitter System –to chemically compensate for deficits/excess Alcohol Consumption Record, Substance Use History & Comprehensive Drinker Profile. Verify with Family Members

Helpful information regarding understanding patterns of drinking/drug use – Refer to ‘Drug Index’ in book which lists of drugs and their neurochemical/ neurotransmitters agonistic and antagonistic effects. Diagram 2 – Effects of Drug Abuse Example- Cocaine Addiction, Genetically Depressed Patient

• Explore findings on Neurotransmitter

pubmed.com. How Acetylcholine

specific drugs Endocannabanoid [stimulate/inhibit] }Serotonin production of affected neurotransmitters. GABA [slight] • Patient chooses drugs Glutamate D1, D2 that boost lacking/low Dopamine neurotransmitters. Noradrenaline Opiate Diagram 2 – Effects of Drug Abuse • Example - Cocaine Addiction on Genetically Depressed Patient • How the drug influences original genetic deficiencies • Arrows show if drug influences [stimulates/inhibits] production of affected neurotransmitter. Effect of self-medication. Neurotransmitter Condition X Alcoholism Acetylcholine Bipolar Endocannabanoid Anxiety Serotonin Depression X GABA Schizophrenia [slight] Glutamate Drug Addiction X D1, D2 Agonist Eating Disorders Dopamine PTSD Noradrenaline Other Opiate Diagram 1 & 2 Match-Up Action of Drug –Self Medication produces Desired Effect (Balance) in Diagram 2 cancels out any Deficiencies in Diagram 1. Diagram 2 Diagram 1 Neurotransmitter Acetylcholine Endocannabanoid

Serotonin GABA Self-Medication [slight] ? Glutamate } Dopamine D1, D2 Agonist Noradrenaline Opiate Address & Analyze Patient Neurochemical Imbalance 3 Withdrawal/detoxification alters neurotransmitter levels. 1. Pattern parallels/surpasses initial assessment in Genetic Deficiencies. 2. More likely will rebound with Withdrawal/Detox affect. Diagram 3 – Anticipating Effect of Withdrawal on Neurotransmitter Levels • Neurochemical imbalances caused by drugs will to withdrawal

Effect of withdrawal once cocaine is discontinued. Diagram 3 –Withdrawal • Withdrawal = Brain’s method of up-regulation. • (Returning Brain’s neurochemical balance to original genetic baseline.) • Severe agitation

Could signify by negative or minus sign “-” in areas of down arrows. -- Address & Analyze Patient Neurochemical Imbalance 4 Medications balance Neurotransmitter levels. 1. Review medication to block the ‘high’. 2. to lower specific neurotransmitters 3. to raise specific neurotransmitters Diagram 4 – The Treatment Plan After viewing Diagrams 1, 2 & 3; consider how to eliminate craving once the drugs of choice are removed. • Visualize ALL corrective measures. • Show effects of Medications use to correct: 1) Genetic Deficiencies, 2) Drug Abuse, 3) Withdrawal. Diagram 4 –Treatment Diagram All Corrective Measures • Close up –Detail Medication affects to remedy depression & cocaine addiction

Neurotransmitter Acetylcholine Endocannabanoid Serotonin Medication – depends on symptoms GABA

Glutamate Slowly Noradrenaline Opiate Why Use These Diagrams? • Visualization through diagrams emphasizes which neurotransmitters impact: 1) Drug Use, X 2) Mental Status & Neurotransmitter 3) Neurotransmitter Acetylcholine Endocannabanoid Inadequacies Serotonin 4) Greatly Improve GABA Quality & Outcome Glutamate of Patient TreatmentDopamine 5) Science-Based, Noradrenaline not Intuition Opiate Why Use These Diagrams? • Improve skills in gathering the right Information

1) Genetic Makeup, 2) Desired Drugs Neurotransmitter X 3) Last Use of Drug Acetylcholine 4) Current Feelings Endocannabanoid 5) Level of Craving Serotonin If uncertain, take GABA no action. Instead, Glutamate Gather more Data! Dopamine Noradrenaline Opiate Diagrams – Valuable to Field of Detoxification • Confused? Learn more of neurotransmitter systems • Practice with patients until proficient • Look at drugs in a new way: actions on neurotransmitter sites & chain reaction effects. X Neurotransmitter Acetylcholine Endocannabanoid Serotonin GABA Glutamate Dopamine Noradrenaline Diagram Synopsis 1)Genetic Baseline of Neurochemical Deficiencies – Note the Imbalance! 2)Drugs addicted to & affected Neurotransmitters 3)How Detox alter Neurotransmitter levels 4)Corrective Medications used for a) Safe Withdrawal b) Rids Cravings Neurotransmitter X c) Correct Genetic Imbalance Acetylcholine Endocannabanoid Serotonin which led to addiction GABA Glutamate Dopamine Noradrenaline Opiate Caveat

Dr. Von Stieff • All medications must be used with caution • High degree of variability between each individual’s brain chemistry and the reaction to drugs. • Caveat: Drug Index in his book is not a guide, but it is a list for general understanding. Before Using These Diagrams Be familiar with the effects of alcohol and drugs upon each of the neurotransmitters. Be familiar with the effects of the therapeutic medications as well. 1. /Trauma/MI 2. Drug of Choice 3. Detox 4. Adjusting levels 1. Genetics/Trauma/MI 2. Drug of Choice 3. Detox 4. Adjusting levels 1. Genetics/Trauma/MI 2. Drug of Choice 3. Detox 4. Adjusting levels 1. Genetics/Trauma/MI 2. Drug of Choice 3. Detox 4. Adjusting levels 1. Genetics/Trauma/MI 2. Drug of Choice 3. Detox 4. Adjusting levels

Responsible , Schizophrenia (if (Schizophrenia, mood & Glutamate for sending signals Alcohol too low or too anxiety disorders) – between high), mood currently in development . nerve cells & disorders, (ADHD)- plays an anxiety , important role in & disorders, (OCD & Tourette’s memory. ADHD, OCD, syndrome)- Topiramate , . Pregabalin 1. Genetics/Trauma/MI 2. Drug of Choice 3. Detox 4. Adjusting levels 1. Genetics/Trauma/MI 2. Drug of Choice 3. Detox 4. Adjusting levels 1. Genetics/Trauma/MI 2. Drug of Choice 3. Detox 4. Adjusting levels Why Use These Diagrams?

These are at best approximations as there is no perfect drug profile for each patient. It is a work in progress. Reported success rate of 85% without relapse. Address & Analyze Patient Neurochemical Imbalance 1. Genetics/Trauma/MI 2. Drug of Choice 3. Detox 4. Adjusting levels Let’s Begin! Diagram 1: Genetic Ailment Genetic Deficiencies, Predispositions in Family -Stress/Mental Illness, Trauma • Client Information within intake forms • Current Disposition & Background History • Craving • Past/present drug use with diagram to illustrate genetic balance of neurotransmitters: Too much/little? • Reflects neurotransmitter balance prior to using any drugs. Diagram 1: Show Genetic Ailment • Jot down information next to the diagram overall genetic predispositions that run the family (viz., family history of alcoholism, bipolar disorder, schizophrenia, etc.). • Genetic Diagram of patient • Addicted to Cocaine • Dx Depression Image page 206 ?

5HT2A ? Diagram 2: Show Drug Effects • Diagram illustrates how drugs influence original neurochemical genetic deficiencies/overabundance • Include drugs that patient uses/craves & draw arrows to illustrate stimulation [arrow up], or inhibition [arrow down ] for each affected neurotransmitter. • Rule of thumb: Drugs patient uses most account for neurotransmitters lacking in system. • [Self Medication]. Action of drugs typically cancel out deficits found in first diagram. Diagram 2: Show Drug Effects • Effects of cocaine on genetically depressed patient.

Image on page 207 D1, D2 Diagram 3: Anticipating Effects of Withdrawal on Neurotransmitter Levels • In chemical dependency- + what goes down must come up. & vice versa. - Diagram 3: Anticipating Effects of Withdrawal on Neurotransmitter Levels • Neurochemical imbalance caused by drugs to withdrawal if drug use was significant to cause the down-regulation of their systems. Diagram 3: Anticipating Effects of Withdrawal on Neurotransmitter Levels • Effects of withdrawal - cocaine discontinued.

D2

Image on page 208 Diagram 3: Anticipating Effects of Withdrawal on Neurotransmitter Levels • Withdrawal = brain’s method of up- regulation. • Up-regulation = returning the brain’s neurochemical balance to its original genetic baseline. • Withdrawal - observable symptoms: significant agitation, other unfavorable symptoms associated with detoxification. Diagram 3: Anticipating Effects of Withdrawal on Neurotransmitter Levels • Place large negative signs ‘—’ or 1 or 2 arrows pointing down near each circle that represents the affected neurotransmitter system. • Purpose: help to visualize what is going to occur if those drugs are stopped and patient goes into withdrawal. Diagram 3: Anticipating Effects of Withdrawal on Neurotransmitter Levels • EXAMPLE: Withdrawal of Opiates ( or OxyContin). Decrease in GABA, Dopamine and Opiates [arrows all pointing down]. Diagram 3: Anticipating Effects of Withdrawal on Neurotransmitter Levels • EXAMPLE: Withdrawal from alcohol. Decrease in Serotonin, GABA and Dopamine; increase in Glutamate. Diagram 3: Anticipating Effects of Withdrawal on Neurotransmitter Levels • EXAMPLE: Withdrawal from . Decrease in Dopamine and Noradrenaline. Diagram 3: Anticipating Effects of Withdrawal on Neurotransmitter Levels • EXAMPLE: Withdrawal from . Extremely low GABA. Insight: Diagrams 1, 2 and 3 can shed light on underlying mental disorders such as Bipolar Disorder.

1 2 3

+ + = Caveat: Anticipate in advance what the patient’s neurological level will be while in acute withdrawal. To do so will ensure smooth progress during detoxification. Sketching out Diagrams 1, 2 and 3

• Will provide essential information on how to eliminate cravings once the drug(s) of choice is/are taken away. • Analyze this carefully to take corrective measures with medications that will stop cravings. Diagram 4: The Treatment Plan

• Use this diagram to plan treatment for patient detoxification, cravings and other disorders like depression. • Diagram the effect each medication has on the patient’s , including any discrepancies, or overlying conflict between the effects of medication. Diagram 4: The Treatment Plan • Treatment diagram - Display of the effect of each medication when remedying depression & cocaine addiction. Image on page 210 Why Use These Diagrams? • Visualization assists in understanding. • Writing them down assists as a quick reference. • Process: to see quickly which neurotransmitters have significant impact on patient drug use, mental status, and or other neurotransmitter- influenced inadequacies. Why Use These Diagrams? These are approximations as there is no perfect drug profile for each patient. It is a work in progress. Using These Diagrams Key points of focus: 1) Practice 2) Become adept at gathering information from the patient 3) Utilize basic data forms to gather information uniformly 4) Use information about family and determine genetic makeup and the drugs have been used by other family members.[This will give you an insight into the specific patient]. 5) Carefully note any adverse reactions to drugs. 6) Include notations as when the patient’s last use of the drug, how the patient feels currently, & what the patient is craving. Diagrams -Synopsis • When in doubt, when uncertain— get more data. Do not throw darts in the dark. Making a hasty decision when there is uncertainty is dangerous. • After gathering more data, organize data into a coherent structure which is plausible. Evaluate danger with opportunity, take action, watch for change and positive results. • Be familiar with the Drug Index on pages 217- 220. Nota Bene: rapid advances in research findings are crucial in updating this index. Genetics/Trauma/MI

Diagram 1- patient neurotransmitter system reveals genetic baseline profile of neurochemicals from birth. Probably reflects an imbalance. Drug(s) of Choice Diagram 2- List of addictive drugs/ substances taken and resultant neurotransmitter levels: stimulating/ inhibiting & to what degree. Detox Diagram 3- How detoxification alters neurochemical levels. Adjusting levels Diagram 4- Illustration of what happens to patient’s neurochemical levels once medication is administered. A) Assists in a safe withdrawal process. B) Helps to reduce the level of cravings. C) Corrects genetic imbalances leading to . Diagram Synopsis Diagram 1- patient’s neurotransmitter system revealing genetic baseline profile of neurochemicals from birth. Probably reflects an imbalance. Dr. Fred Diagram 2- List of addictive substances/drugs Von taken and resultant neurotransmitter levels: Stieff stimulating/. inhibiting & to what degree. Diagram 3- How detoxification alters neurochemical levels. Diagram 4- Illustration of what happens to patient’s neurochemical levels once medication is administered. A) Assists in a safe withdrawal process. B) Helps cravings. C) Corrects genetic imbalances leading to addictions. Practice! III. GABA versus Glutamate Gamma-Aminobutyric Acid acts as an inhibitory neurotransmitter Gamma-Aminobutyric Acid Glutamate – Brain Agitator – Most abundant excitatory neurotransmitter Blue Blue ‘Unglue’-timate Brain Agitate

Glutamate Alcohol Withdrawal - Seizures Brain Attempts to Rebalance- With Self Medication DID YOU KNOW THAT A Brain with High Glutamate Levels is Agitated?

Result: Brain Stimulation & Activation Gets off to a quick start.Who But wins fades in after a a mile.race?

OffIt depends to a slow .start. . . Builds momentum in the long run. . . . On how far you go! The GABA and Glutamate Balance

Consuming Alcohol Raises GABA levels QUICKLY Glutamate [agitate] levels rise more slowly Consuming more Alcohol Raises GABA levels even more Glutamate [agitate] levels will continue to rise. Consuming even more Alcohol Raises GABA levels Glutamate [agitate] levels continue to catch up. NO LONGER Consuming Alcohol causes GABA levels to drop Glutamate [agitation] levels Cravings CRAVINGS rise more quickly & CRAVINGS CRAVINGS begin Seizure Line

GABA plummets! No Alcohol for some . CRAVINGS get worse. Cravings Glutamate levels high & CRAVINGS Seizures begin. CRAVINGS , glutamate antagonist, is useful in alcohol dependence. Topiramate, glutamate antagonist & GABA agonist, useful in alcohol dependence.

Seizure Line

Topomax & Campral boost GABA Level Analogy: Pull thumb Overuse of Too Much Valium [Diazepam] GABAa1 VERY PREDICTABLE => VERY UNPREDICTABLE

Overuse produced tolerance Bev Grandma paradoxical effect inciting agitation

Aziz Aaron

Unopposed Site Barb becomes disabled burned out Use other 5 GABA Sites Alcohol Main Point

• Severity of withdrawal symptoms depends on the imbalance between Glutamate and GABA levels • Severity of withdrawal does not depend on the amount of alcohol consumed. Acute Alcohol Withdrawal Syndrome • Detoxification Treatment = returning patients neurotransmitters to normal genetic state as safely as possible. • Severity of withdrawal does not depend on the amount of alcohol consumed. • Severity of withdrawal symptoms depends on the imbalance between Glutamate and GABA levels. • Severity of withdrawal depends on malnutrition and dehydration. Acute Alcohol Withdrawal Syndrome (AWS) -three levels • 1) Mild Withdrawal- • 2) Moderate Withdrawal- • 3) Severe Withdrawal- Acute Alcohol Withdrawal Syndrome

• AWS 1) Mild Withdrawal- -very shaky, no tremens. Some tremors and hypertension. • GABA-Glutamate differential mild. Acute Alcohol Withdrawal Syndrome • AWS –2) Moderate Withdrawal- greater discrepancy between GABA & Glutamate levels. • Greater imbalance manifests in hypervigilant state, rapid , supraventricular tachycardia and severe agitation. Acute Alcohol Withdrawal Syndrome • AWS 3) Severe Withdrawal- Glutamate exceedingly high/ GABA incredibly low. • & visual , possible seizures. Harnessing the Power of Neurotransmitters

Campral - medication used with counseling in treating alcohol dependence. Harnessing the Power of Neurotransmitters

Prozac, [SSRI]- raises Serotonin levels. More positive thoughts, feeling better. Balances neurotransmitters, to correct compulsivity, neuroticism & improve quality of life. IV. Brain Scans and the Future Since we are ‘shooting for the stars’ what if we look to the future for a clue?

Demonstration: • Need 1 Volunteer Star Trek NG Tricorder Brain-Scan for Level of Activity

Scan 1 Scan 2 The Human Connectome Project http://www.humanconnectomeproject.org/ • Navigate the brain in a way that was never before possible; fly through major brain pathways, compare essential circuits, zoom into a region to explore the cells that comprise it, and the functions that depend on it. Imagine: Future Computerized Diagram Format Will utilize the graphic display for each stage:

1) Trauma, Genetic Predisposition, Stress problems, Mental Disorders 2) Self Medicating (Chemical Dependency) 3) Withdrawal

4) Stabilization 1) Genetic deficiencies/trauma/Mental Illness- patient tries to balance this new self-medication [alcohol & drugs]. 2) Drugs & alcohol affect neurotransmitter levels. 3) Withdrawal/detoxification alters neurotransmitter levels. 4) Medication affecting balance of neurotransmitters for stabilization & recovery. Systems seek a natural balance. Remember! •Trauma •Genetic Predisposition •Stress problems •Self Medicating (Chemical Dependency) •Mental Disorders Summary

• Addiction – a dreaded disease. With proper treatment the brain can return to proper balance. Thank you! Questions ???? [email protected]