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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
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 pillsLunesta, Ambien, Restoril
Cheat Sheet con’t
• Hallucinogens: LSD, Mescaline, Peyote,
Psilocin or ‘shrooms
• Dissociatives: Phencyclidine, Ketamine,
Dextromethorphan, PCP
• Inhalants: Nitrite, NO, Toluene, Butane
• Dissociatives/Stimulants: MA, NMDA
Cheat Sheet con’t
• 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
CONTACT INFORMATION
•
•
•
•
540-688-2426
[email protected]
9 Pinnacle, Ste 105, Fishersville, VA 22939
Physician Clinical Support System Mentor,
SAMHSA, www.PCSSmentor.org
II have
have disclosed
disclosed that
that I do not
have a financial relationship or
interest
interest with any proprietary
proprietary
entity
entity producing healthcare
healthcare
goods or services in
conjunction with this
conference.
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
PLEASE STOP ME WITH QUESTIONS
The United States of Drugs
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
John Deskins con’t
• 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
TERMINOLOGY!!!!!
Higher
Brain
A=Addiction
A
P
P=physical
tolerance, withdrawal
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)
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 antihypertensive 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!!!!!!!!
Physical Adaptations
• 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 can’t get his/her fix and becomes nauseated,
shaky and sick.
SOLUTION: WEAN SLOWLY!!!!!
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
“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
HIGHER BRAIN PROBLEMS
• DIVERSION
• SUBSTANCE ABUSE
• ADDICTION
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.”
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.”
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!!!!!!!!
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!
HOW DO YOU KNOW IF A RAT HAS
ADDICTION?
Food, Water, Procreating,
Taking Care of Young
SUBSTANCE
Food, Water,
Reproducing, taking
Care of Young
SUBSTANCE
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
– CAN’T STOP WITHOUT HELP
• OBJECTIVE SYMPTOM: SUB-OPTIMAL
FUNCTIONING
• SUBJECTIVE SYMPTOM: CRAVINGS
HOW DO YOU MAKE AN ADDICTED RAT?
(OR HUMAN?)
GENETIC PREDISPOSITION
PLUS
EXPOSURE TO SUBSTANCE
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)
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
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
Well, This Is One Way Around That Pesky
“Slow Release”
Abused
Oxycontin
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
Heroin, cocaine, IV Dilaudid, Nicotine,
Snorted/Injected Oxycontin (old
formulation), Xanax
Increase
in
dopamine
Percocet, Immediate Release Morphine,
Higher Proof Liquor, non-injected
Oxycontin, Vicodin
Abused Methadone, Abused
Buprenorphine, Lower Proof
Alcohol, Marijuana
Rate of increase, fast to slow
Methadone, Buprenorphine
taken as directed
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) $816,000
• Methadone 1$ per milligram
• Percocet 10mg $32/pill (8/25/11 personal report)
* Beard, J Tobias, “Coke is the Real Thing; Fifty bucks and you’re in with Charlottesville’s favorite powder”, C’VILLE CHARLOTTESVILLE NEWS & ARTS, 2/11/2008
Non-controlled substances with street
value
•
•
•
•
•
•
Muscle Relaxants
Neurontin
Remeron
HIV medications
Prednisone
ULTRAM!!!!!!!!! (Now controlled)
It’s not about the Substance.
It’s about the Brain.
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)
PUTTING IT ALL TOGETHER
ADDICTION
STARTS AGE
36
Inherited Threshold for Addiction
Z
Y
Cumulative
Dopamine
Spikes
X
AGE
10
15
20
25
30
35
40
45
ADDICTION
STARTS AGE
24
Inherited Threshold for Addiction
Z
More frequent
exposure
Cumulative
Dopamine
Spikes
Y
Social Norms
Self-medicating
(PTSD, abuse, underlying psychpathology)
Sociopathy
X
AGE
Poor Parenting
10
15
20
25
30
35
40
45
Inherited Threshold for Addiction
Z
ADDICTION
STARTS AGE
20
Lower
inherited
threshold
Onset of
Addiction
Y
Cumulative
Dopamine
Spikes
X
AGE
10
15
20
25
30
35
40
45
Starting
Substance Use
Earlier
decreases the
threshold
Inherited Threshold for Addiction
Z
ADDICTION
STARTS AGE
20
Onset of
Addiction
Y
Cumulative
Dopamine
Spikes
X
AGE
10
15
20
25
30
35
40
45
NO Threshold for Addiction
Cumulative
Dopamine
Spikes
AGE
10
15
20
25
30
35
40
45
ADDICTION
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; 162:1414–1422)
Rifles
Shot Guns
SCATTER
ALL Medications are Shot Guns
example: Aspirin
Target: Pain control (4 hours)
Thins blood (30 days)
Irritates stomach (immediate)
Opioids are also Shot Guns
Pain control
Respiratory Depression
Constipation
Dopamine Spike
Or Addictive
Liability Or
Psychoactive
Properties
Tolerance to
Respiratory
Depression
Tolerance
To Dopamine
Spike
Changing the molecule to change the
target
Not to scale, not exact organic
compounds, for illustration
Only.
Add an OH group,
Longer acting
Add an ring,
More pain relief
Add an N,
More psychoactive
Add an N and a chain,
Doesn’t cross blood brain
Barrier, constipates only
Finally (on the subject of Organic Chemistry)
• TARGETS are variable!!!
• i.e. Every BRAIN is different!!!
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
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
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 haven’t figured it all
out yet.
• Good EBM that they are effective for the disease of
Addiction
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 don’t
defend themselves.
12 STEP PROGRAMS
• Effective (Not Perfect)
• Accessible
• Lifelong and FREE
– When you hear “We’re not a 12 Step Program. We
REALLY work,” ask:
• Is what you’re 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? (Don’t let the critics re-define Addiction as an
acute disease)
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??????
What Damage do substances of abuse do
to Brains?
• Toxins and Free Radicals
• Predispose to the Development of Addiction
Brains don’t 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
“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
“PAIN” vs. “SUFFERING”
EMOTIONAL
PHYSICAL
SPIRITUAL
“PAIN” vs. “SUFFERING”
EMOTIONAL
PHYSICAL
WHOLE PERSON
SPIRITUAL
THERE’S A LOT OF SUFFERING GOING
ON (AND IT ALL GOES ON IN THE BRAIN!)
(AND THERE’S A LOT MORE COMING.)
Treating Addiction
• Don’t just Detox!!!!!
• COUNSELING
– 12 Step meetings
– Others (if available and affordable)
• Adjunct Medications
– Minority of patients
LEVELS OF CARE
Diabetes
Inpatient, IOP
Plus Insulin Plus Methadone Clinic
Addiction
Plus Oral Medication Plus Outpatient Buprenorphine Tx
Basic Diabetic Teaching Plus
Dietician Monitoring
Basic Diabetic Teaching and
Home Blood Sugar Monitoring
12 Step Participation
Plus Addiction Specific
Professional Counseling
12 Step Participation
ADJUNCT TO COUNSELING:
MEDICATION ASSITED ADDICTION TREATMENTprimarily 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
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
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!!!!!!
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 isn’t a relapse isn’t a relapse
• ASAM Placement Criteria
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-naïve
– < 3% endorse buprenorphine as their substance of
choice - Cicero
• To be diverted to pay for substance of choice
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.
Am J Addict. 2004;13 Suppl 1:S17-28.
French field experience with buprenorphine.
Auriacombe M1, Fatséas M, Dubernet J, Daulouède 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]
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 (nondefined scatter).
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? YOU’RE RIGHT!!!!
ALL YOU’LL EVER NEED TO KNOW
ABOUT URINE DRUG SCREENS!!!
1. ALWAYS call and clarify unexpected results
1.
You’re paying for this service, USE IT
2. They are very seldom WRONG
3. You’re only responsible for doing the best
you can
• If the patient gets by with something this time, their
good luck won’t last forever
“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
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)
REFERENCES
•
•
•
•
DON’T TAKE MY WORD FOR IT
DON’T TAKE ANYONE’S WORD FOR IT
GET THE FACTS
CHECK THE REFERENCES
Sources of Information
• www.casacolumbia.org
• Monitoring the Future, NIDA
– 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
A Few References
• REMS CO*RE, ER/LA Opioid REMS, Completer
Slide Deck, www.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.
FREE, GOOD EDUCATION!!!
• http://pcssmat.org/educationtraining/archived-webinars/