Slide 1

The Science Behind the Disease of Addiction and How It Binds Us All Together Virginia Summer Institute on Addiction Studies July 14, 2015 Mary G. McMasters, MD, FASAM

Slide 2

Cheat Sheet Stimulants: Caffeine, ritalin, Adderall, methamphetamine, cocaine, nicotine Depressants: Pain Pills (Opiates) including Vicodin, Percocet, Morphine, Opium, Heroin, Oxycontin, Dilaudid, Tramadol (Ultram), methadone, Suboxone (buprenorphine) Depressants: ETOH (alcohol) and BNZs (benzodiazepines) including tranquilizers- Xanax, Valium, Librium, Ativan, clonazepam, sleeping pills- Lunesta, Ambien, Restoril

Slide 3

Cheat Sheet cont Hallucinogens: LSD, Mescaline, Peyote, Psilocin or shrooms Dissociatives: Phencyclidine, Ketamine, Dextromethorphan, PCP Inhalants: Nitrite, NO, Toluene, Butane Dissociatives/Stimulants: MA, NMDA

Slide 4

Cheat Sheet cont Buprenorphine- mixed opioid agonist/antagonist, structure- ultra synthetic opioid (Imodium is also an ultra synthetic opioid) Naloxone- only active if taken IV (not by mouth of if snorted), Full opioid antagonist Suboxone, Bunavail and Zubsolv= Buprenorphine + Naloxone Subutex= Buprenorphine

Slide 5

CONTACT INFORMATION 540-688-2426 mmcmasters@chsonline.net 9 Pinnacle, Ste 105, Fishersville, VA 22939 Physician Clinical Support System Mentor, SAMHSA, www.PCSSmentor.org

Slide 6

I have disclosed that I do not have a financial relationship or interest with any proprietary entity producing healthcare goods or services in conjunction with this conference.

Slide 7

Mary G. McMasters, MD, FASAM Board Certified Addiction Medicine Appointee, Gov. McAuliffe, Task Force on Prescription Drug Abuse and Heroin Hospice/Palliative Care Physician Co-Medical Director Project REMOTE Expert Witness USDOJ Adjunct Instructor DEA FELLOW, AMERICAN SOCIETY OF ADDICTION MEDICINE Old Country Addictionologist

Slide 8

PLEASE STOP ME WITH QUESTIONS

Slide 9

The United States of Drugs

Slide 10

The Cost of Prescription Drug Abuse John Deskins, Bureau Business and Economy, WVU Presentation Appalachian Drug Summit, USDOJ, 2013, Johnson City, TN 2013- estimated 62 billion lost 4% drug abuse tx 2% medical complications 15% criminal justice costs including victims 79% lost productivity Premature death Unemployment Subemployment Does NOT account for multipliers

Slide 11

John Deskins cont Per year: WV- entire state and local government spending on police KY- entire amount spent on elementary and secondary education TN- entire amount spent on highways annually

Slide 12

PP=physical tolerance, with- drawal Higher Brain A A=Addiction TERMINOLOGY!!!!!

Slide 13

Physical Adaptations Tolerance and Dependence PHYSICAL Physiological adjustment to MANY medications Anti-depressants Anti-hypertensives NOT the same thing as the substance misuse disorders (diversion, substance abuse and addiction)

Slide 14

Physical Adaptations Tolerance: it takes more of a substance (therapeutic or non-therapeutic) to achieve a goal (therapeutic or non-therapeutic) Ex: A patient needs more beta blocker (an anti- hypertensive medication) to control their blood pressure A regular user of Oxycontin can tolerate a dose which would make a non-user stop breathing. TOLERANCE NORMALLY HAS A CEILING!!!!!!!!

Slide 15

Physical Adaptations withdrawal syndrome Physical Dependence: the sudden cessation of a substance to which the body has become accustomed (therapeutic or non-therapeutic) results in a withdrawal syndrome Ex: A physician stops a beta blocker abruptly without weaning it and the patient feels panicky, has high blood pressure and a fast heart rate An opiate addict cant get his/her fix and becomes nauseated, shaky and sick. SOLUTION: WEAN SLOWLY!!!!!

Slide 16

Opioid Withdrawal Can be miserable for some people Some people may have none to little even with cold turkey weans. Usually not life threatening Repeated HARD, cold turkey detox episodes leads to MORE substance abuse, not less Risks and Benefits

Slide 17

Detox -Detox = weaning - Detoxification only treats the physical dependence, NOT the Addiction - Patients who are detoxified lose their tolerance to respiratory depression -When they resume substance use, they are likely to die -FACTOID: Harrison Narcotics Act 1914, doctors allowed distribution "in the course of his professional practice only." This clause was interpreted after 1917 to mean that a doctor could not prescribe opiates to an addict *Heit HA; Dear DEA, Pain Medicine Vol 5 #3, 2004, 303-308

Slide 18

HIGHER BRAIN PROBLEMS DIVERSION SUBSTANCE ABUSE ADDICTION

Slide 19

HIGHER BRAIN PROBLEMS SUBSTANCE ABUSE the substance use is continued despite knowledge of having a persistent or recurrent physical or psychological (or social or occupational) problem that is likely to have been caused or exacerbated by the substance.

Slide 20

HIGHER BRAIN DISEASE: ADDICTION the substance use is continued despite knowledge of having a persistent or recurrent physical or psychological (or social or occupational) problem that is likely to have been caused or exacerbated by the substance. persistent desire or unsuccessful efforts to cut down or control substance use.

Slide 21

Addiction Repeatedly doing something which is BAD for you (not just bad) Cannot stop doing it without help CHRONIC BRAIN DISEASE with reproducible pathophysiology (anatomical, chemical, genetic) IT ALL COMES DOWN TO FUNCTIONING!!!!!!!!

Slide 22

NOT ADDICTION IS NOT SUBSTANCE SPECIFIC Preferences Due to SIDE EFFECTS VERY generally: Externalizers (outgoing, hyperactive, very social) prefer downers Internalizers (depressed, shy) prefer uppers ADDICTION HAS NO BRAND LOYALTY!

Slide 23

Slide 24

HOW DO YOU KNOW IF A RAT HAS ADDICTION?

Slide 25

Food, Water, Procreating, Taking Care of Young SUBSTANCE

Slide 26

Food, Water, Reproducing, taking Care of Young SUBSTANCE

Slide 27

Slide 28

HOW DO YOU KNOW IF A HUMAN HAS ADDICTION? WILL CHOOSE THE SUBSTANCE INSTEAD OF: TAKING CARE OF THEMSELVES, THEIR FAMILIES, THEIR RELATIONSHIPS AND THEIR LIVES CANT STOP WITHOUT HELP

Slide 29

OBJECTIVE SYMPTOM: SUB-OPTIMAL FUNCTIONING SUBJECTIVE SYMPTOM: CRAVINGS

Slide 30

HOW DO YOU MAKE AN ADDICTED RAT? (OR HUMAN?) GENETIC PREDISPOSITION PLUS EXPOSURE TO SUBSTANCE

Slide 31

PART 1: GENETIC PREDISPOSITION SOME RATS/HUMANS GET A LITTLE SOME RATS/HUMANS GET A LOT SOME RATS/HUMANS HAVE NONE!!!! SCIENTISTS CAN MOVE THE GENES AROUND (IN RATS, NOT HUMANS- YET)

Slide 32

Slide 33

Slide 34

PART 2: EXPOSURE TO SUBSTANCES WHAT MAKES A SUBSTANCE ADDICTIVE? ELEVATES DOPAMINE IN THE FOREBRAIN ABOVE LEVELS NORMALLY SEEN IN NATURE A. FAST B. HIGH THE FASTER AND THE HIGHER, THE MORE ADDICTIVE A SUBSTANCE IS

Slide 35

Slide 36

How Quickly can you get chemicals into the brain? Swallowing- VERY Slow Taking on an Empty Stomach- Slow Inhale- Fast Inject into Blood- VERY Fast

Slide 37

Well, This Is One Way Around That Pesky Slow Release Abused Oxycontin

Slide 38

Once Inside the Brain, What do Substances of Abuse DO? Trigger the Natural Reward System Increase Dopamine in the Forebrain The FASTER The HIGHER THE MORE ADDICTIVE MANY more things than Abused Substances can trigger this system

Slide 39

Increase in dopamine Rate of increase, fast to slow Heroin, cocaine, IV Dilaudid, Nicotine, Snorted/Injected Oxycontin (old formulation), Xanax Percocet, Immediate Release Morphine, Higher Proof Liquor, non-injected Oxycontin, Vicodin Abused Methadone, Abused Buprenorphine, Lower Proof Alcohol, Marijuana Methadone, Buprenorphine taken as directed

Slide 40

Street Value 100 Vicodin $500-$800 100 Xanax 2mg $1,000 4 Fentanyl patches 100ug $400 100 Dilaudid 8mg $8-10,000 100 Oxycontin 80mg (old formulation) $8- 16,000 Methadone 1$ per milligram Percocet 10mg $32/pill (8/25/11 personal report) * Beard, J Tobias, Coke is the Real Thing; Fifty bucks and youre in with Charlottesvilles favorite powder, CVILLE CHARLOTTESVILLE NEWS & ARTS, 2/11/2008

Slide 41

Non-controlled substances with street value Muscle Relaxants Neurontin Remeron HIV medications Prednisone ULTRAM!!!!!!!!! (Now controlled) Its not about the Substance. Its about the Brain.

Slide 42

Who is Using??? PATIENT A : Cigarette smoker? PATIENT B: The patient taking Suboxone as prescribed for the disease of Addiction? (Remember, Using = elevating dopamine ABOVE levels normally experienced in nature)

Slide 43

PUTTING IT ALL TOGETHER Inherited Threshold for Addiction AGE 15 10 20 25 3035 4045 Cumulative Dopamine Spikes X Y Z ADDICTION STARTS AGE 36

Slide 44

Inherited Threshold for Addiction AGE 15 10 20 25 3035 4045 More frequent exposure X Y Z ADDICTION STARTS AGE 24 Cumulative Dopamine Spikes Self-medicating (PTSD, abuse, underlying psychpathology) Sociopathy Poor Parenting Social Norms

Slide 45

Inherited Threshold for Addiction AGE 15 10 20 25 3035 4045 Onset of Add iction Lower inherited threshold X Y Z Cumulative Dopamine Spikes ADDICTION STARTS AGE 20

Slide 46

Inherited Threshold for Addiction AGE 15 10 20 25 3035 4045 Onset of Add iction X Y Z Cumulative Dopamine Spikes ADDICTION STARTS AGE 20 Starting Substance Use Earlier decreases the threshold

Slide 47

NO Threshold for Addiction AGE 15 10 20 25 3035 4045 Cumulative Dopamine Spikes

Slide 48

Addiction: A Disease of Learning and Memory Steven E. Hyman, M.D. If neurobiology is ultimately to contribute to the development of successful treatments for drug addiction, researchers must discover the molecular mechanisms by which drug-seeking behaviors are consolidated into compulsive use, the mechanisms that underlie the long persistence of relapse risk, and the mechanisms by which drug-associated cues come to control behavior. Evidence at the molecular, cellular, systems, behavioral, and computational levels of analysis is converging to suggest the view that addiction represents a pathological usurpation of the neural mechanisms of learning and memory that under normal circumstances serve to shape survival behaviors related to the pursuit of rewards and the cues that predict them. The author summarizes the converging evidence in this area and highlights key questions that remain. (Am J Psychiatry 2005; 162:14141422) ADDICTION

Slide 49

Slide 50

Rifles

Slide 51

Shot Guns SCATTER

Slide 52

ALL Medications are Shot Guns example: Aspirin Target: Pain control (4 hours) Thins blood (30 days) Irritates stomach (immediate)

Slide 53

Opioids are also Shot Guns Pain control Constipation Dopamine Spike Or Addictive Liability Or Psychoactive Properties Respiratory Depression Tolerance to Respiratory Depression Tolerance To Dopamine Spike

Slide 54

Changing the molecule to change the target Add an OH group, Longer acting Add an ring, More pain relief Add an N, More psychoactive Add an N and a chain, Doesnt cross blood brain Barrier, constipates only Not to scale, not exact organic compounds, for illustration Only.

Slide 55

Finally (on the subject of Organic Chemistry) TARGETS are variable!!! i.e. Every BRAIN is different!!!

Slide 56

ADDICTIVE LIABILITY IS NOT THE SAME THING AS PAIN RELIEVING POTENCY!!! Equals how fast/high a substance elevates dopamine in the forebrain Equals POTENCY Low potency One dollar buys a pack of gum Small Slow Dopamine Spike High potency One dollar buys a house Big Fast Dopamine Spike

Slide 57

BRAINS ARE PLASTIC!!!! HOW BRAINS HEAL Repair Rewiring This is why counseling and 12 step participation IS NOT HOCUS-POCUS!!!!! Galanter M, Spirituality, Evidence-Based Medicine, and Alcoholic Anonymous, Am J Psychiatry 165:12, Dec 2008

Slide 58

12 STEP PROGRAMS Addiction was not a real medical disease and physicians cannot treat it Harrison Narcotic Act 1914 The affected community had to come up with their own solution 12 Step Programs developed OUTSIDE of medical science (with few exceptions) Like many herbal remedies, there is good science behind 12 Step Programs. We just havent figured it all out yet. Good EBM that they are effective for the disease of Addiction

Slide 59

How To Become Richer than God The pill to cure Addiction Addicts (and their families) are the most vulnerable population in health care Parasites and Predators H. Westley Clarke, MD, former Director of NIDA Bad-mouthing 12 Step Programs to influence research subject pools. 12 Step Programs are Anonymous and dont defend themselves.

Slide 60

12 STEP PROGRAMS Effective (Not Perfect) Accessible Lifelong and FREE When you hear Were not a 12 Step Program. We REALLY work, ask: Is what youre offering effective as shown via Evidence Based Medical Science? The American Society of Addiction Medicine? Is it accessible to EVERY patient EVERY day for the rest of his/her life? (Dont let the critics re-define Addiction as an acute disease)

Slide 61

COUNSELING NOT OPTIONAL FOR PATIENTS ON MAAT (AND MANY OTHERS NOT ON MAAT) NOT OPTIONAL FOR PATIENTS WITH CO-MORBID ISSUES AND A GREAT DEAL OF SOCIAL CHAOS ESSENTIAL THAT COUNSELING WORK TO INTEGRATE PATIENTS INTO THEIR COMMUNITY SUPPORT GROUPS Why is it so much easier to get third party payers to reimburse for the pills which cause the problems than for the counseling which helps to deal with it??????

Slide 62

What Damage do substances of abuse do to Brains? Toxins and Free Radicals Predispose to the Development of Addiction

Slide 63

Brains dont have pain receptors!!! Instead, a damaged brain will become Depressed Anxious Unable to concentrate Unable to coordinate movement Insomniac Abnormally aware of pain (hyperalgesia) Less able to process and understand information Less smart, i.e. have a decreased IQ Maturationally and developmentally impaired These can become permanent

Slide 64

Co-Morbid Psychiatric Diagnoses It is VERY important that NO major mental illness be diagnosed until a patient has been substance free for a long time (in my opinion six months) Many (not all) other psychiatric problems will go away once the brain is given time to heal Medications for depression, anxiety, etc. are NOT effective when other substances are in the brain

Slide 65

PAIN vs. SUFFERING PHYSICAL EMOTIONAL SPIRITUAL

Slide 66

PAIN vs. SUFFERING PHYSICAL EMOTIONAL SPIRITUAL WHOLE PERSON

Slide 67

THERES A LOT OF SUFFERING GOING ON (AND IT ALL GOES ON IN THE BRAIN!) (AND THERES A LOT MORE COMING.)

Slide 68

Treating Addiction Dont just Detox!!!!! Dont just Detox!!!!! COUNSELING 12 Step meetings Others (if available and affordable) Adjunct Medications Minority of patients

Slide 69

LEVELS OF CARE Diabetes Addiction 12 Step Participation Basic Diabetic Teaching and Home Blood Sugar Monitoring Basic Diabetic Teaching Plus Dietician Monitoring 12 Step Participation Plus Addiction Specific Professional Counseling Plus Outpatient Buprenorphine TxPlus Oral Medication Plus Insulin Plus Methadone Clinic Inpatient, IOP

Slide 70

ADJUNCT decrease cravings ADJUNCT TO COUNSELING: MEDICATION ASSITED ADDICTION TREATMENT- primarily decrease cravings Medication- (FDA approved) Nicotine Varenicline Nicotine Replacement Alcohol Acamprosate Naltrexone (pills and injections) Antabuse- AVERSIVE therapy, not effective Opioids Methadone (Methadone Maintenance Therapy- MMT) Buprenorphine

Slide 71

Methadone Can ONLY be obtained in a licensed methadone clinic (for addiction) Methadone clinics are A HIGHER LEVEL OF CARE Crime reduction, death reduction, reduction in transmission of blood borne diseases, increased tax revenues HARM REDUCTION For the sickest of the sickest of the sick Low doses (30-40mg/day) block withdrawal, not cravings

Slide 72

Buprenorphine Can only be obtained from a licensed Buprenorphine provider Should be coupled with counseling and integration into community support groups (12 step) For the sickest of the sick. WITH NALOXONE!!!!!!

Slide 73

BUPRENORPHINE: THE GREAT MOTIVATOR Contingent on participation in counseling Contingent on PROGRESS towards abstinence Identifying the substance of choice Triage substance use Dangerous Not consistent with recovery Plan for RELAPSE A relapse isnt a relapse isnt a relapse ASAM Placement Criteria

Slide 74

Diversion of Buprenorphine and Methadone To avoid physical withdrawal To provide withdrawal-free periods For work Stockpile between shipments of the good stuff Self treatment of Addiction To get high MUST be opioid-nave < 3% endorse buprenorphine as their substance of choice - Cicero To be diverted to pay for substance of choice

Slide 75

End Points (but not of this presentation) Reduce death rate due to opioids Improve functioning Abstinence??? THERE IS A LOT OF HARM REDUCTION ON THE WAY TO ABSTINENCE. !

Slide 76

Am J Addict. 2004;13 Suppl 1:S17-28. French field experience with buprenorphine. Auriacombe M1, Fatsas M, Dubernet J, Dauloude JP, Tignol J. Author information Abstract In most European countries, methadone treatment is provided to only 20-30% of opiate abusers who need treatment due to regulations and concerns about safety. To address this need in France, all registered medical doctors since 1995 have been allowed to prescribe buprenorphine (BUP) without any special education or licensing. This led to treating approximately 65,000 patients per year with BUP, about ten times more than with more restrictive methadone policies. French physician compensation mechanisms, pharmacy services, and medical insurance funding all minimized barriers to BUP treatment. About 20% of all physicians in France are using BUP to treat about half of the estimated 150,000 problem heroin users. Daily supervised dosing by a pharmacist for the first six months resulted in significantly better treatment retention (80% vs 46%) and lower heroin use. Intravenous diversion of BUP may occur in up to 20% of BUP patients and has led to various infections and relatively rare overdoses in combination with sedatives. Opiate overdose deaths have declined substantially (by 79%) since BUP was introduced in 1995. Newborn opiate withdrawal in mothers treated with buprenorphine compared to methadone was reported to be less frequent, less severe, and of shorter duration. Although some of the public health benefits seen during the time of buprenorphine expansion in France might be contingent upon characteristics of the French health and social services system, the French model raises questions about the value of tight regulations on prescribing BUP imposed by many countries throughout the world. PMID: 15204673 [PubMed - indexed for MEDLINE]

Slide 77

How Long? Less than 3 months: useless More than 6 months????? Not willing to do the work Need to work through barriers to recovery Forcing people off of methadone leads to increased death rate Subset where buprenorphine and methadone are treating something other than the cravings (non- defined scatter).

Slide 78

Urine Drug Screens As Organic Chemists have altered the opioid molecule, many opioids are no longer detected by basic (natural) opioid screens Ultra-synthetic opioids must be tested for SEPERATELY: methadone, buprenorphine, ultram (Tramadol) Too much to remember? YOURE RIGHT!!!!

Slide 79

ALL YOULL EVER NEED TO KNOW ABOUT URINE DRUG SCREENS!!! 1.ALWAYS call and clarify unexpected results 1.Youre paying for this service, USE IT 2. They are very seldom WRONG 3. Youre only responsible for doing the best you can If the patient gets by with something this time, their good luck wont last forever

Slide 80

Medico-Legal A UDS is just another lab test HIPAA protects ALL lab tests You need to know what the patient has in his/her system at the time you prescribe a controlled substance Medico-Legal is a term often used to scare prescibers and make more $ for labs

Slide 81

Which Results do you need? Sensitivity- detects True Positives Specificity- detects True Negatives The more Sensitive a test is, the less Specific it is (most of the time) The more Specific a test is, the less Sensitive it is (most of the time)

Slide 82

REFERENCES DONT TAKE MY WORD FOR IT DONT TAKE ANYONES WORD FOR IT GET THE FACTS CHECK THE REFERENCES

Slide 83

Sources of Information www.casacolumbia.org Monitoring the Future, NIDA www.monitoringthefuture.org www.monitoringthefuture.org www.drugabuse.gov www.samhsa.gov www.health.org www.clubdrugs.org www.drugfreeamerica.org www.collegedrinkingprevention.gov www.jointogether.org/sa/news/features

Slide 84

A Few References REMS CO*RE, ER/LA Opioid REMS, Completer Slide Deck, www.core-rems.orgwww.core-rems.org Alford, Compton, Samet; Acute Pain Management for Patients Receiving Maintenance Methadone or Buprenorphine Therapy; Ann Intern Med. 2006;144:127-134. Ballantyne, LaForge; Opioid Dependence and addiction during opioid treatment of chronic pain; Pain 1209 (2007) 235-255.

Slide 85

FREE, GOOD EDUCATION!!! http://pcssmat.org/education- training/archived-webinars/