2015 keynote presentation at the Oregon Counseling Association Conference by Darryl Inaba, PharmD, CATC-V, CADC-III, author of Uppers, Downers, All-Arounders.

1. Current Science of
Recovery:
A Journey into Wellness
ORCA 2015 Fall
Conference
Darryl Inaba, PharmD., CATC-
Eighth Edition

3. Current Science of Recovery will consist
of Two Parts
• Part I: Evolving Science of Addiction
and its current impact on wellness
• Part II: Developments in Addiction
Treatment & Relapse
(Recrudescence) Prevention:
Promoting Long-Term Recovery and
wellness

4. Part I: Evolving Science of Addiction &Part I: Evolving Science of Addiction &
Its Impact on WellnessIts Impact on Wellness
Darryl S. Inaba, PharmD., CATC-V, CADC IIIDarryl S. Inaba, PharmD., CATC-V, CADC III
Director Clinical & Behavioral Health Services - ARCDirector Clinical & Behavioral Health Services - ARC
Director of Research & Education - CNSDirector of Research & Education - CNS

5. Annual U.S. Lives Lost to Addiction
LEGAL:
Tobacco-Nicotine 480,000
Beer/wine/Booze-Ethanol 130,000
Rx Medications- opioids/benzos/etc.
38,000
ALL ILLEGAL DRUGS COMBINED:
(Heroin, methamphetamine, cocaine, etc)
24,000
Consider: Civil War (4 yrs.) 750,000
WWI (2 yrs.) 116,516
WWII (5 yrs.) 405,399
Vietnam (20 yrs.) 58,209
Thus, Deadliest drugs are Legal and now Pot is Legal!
Addiction kills more people in 1 year than 27 years of WWI, WWII & Vietnam

6. Substance-Related and Addictive
Disorders DSM-5 May 18, 2013
• Misconceptions, Misunderstandings, Myths &
Stigma [weak, bad, stupid, crazy]
• 60% illicit drugs sold in suburbia or rural US
• 75% Hard-Core drug users: actively and even
gainfully employed
• <5% Alcoholics fit “Wino” stereotype
• US lifetime prevalence = 30% (Inc. Mensa)
• Irresponsible pleasure seekers: Willful
Misconduct? [James White (2011). 1970 British Cohort Study]

7. Disease/Disorder
A pathological impairment of health or
a condition of abnormal functioning
associated with specific symptoms and
signs caused by internal or external
factors that result in an expected
(predictable) set of discomforts or
dysfunctions
Organ Defect & Cause Symptoms→ →
(Anomaly, Difference)

8. Disease Characteristics
• Chronic (persistent)
• Progressive
• Relapsing
• Incurable but Treatable/Manageable and
often Preventable
• Fatal if untreated
Diabetes analogy to Addiction Disorders
Pathomimetic Symptoms 3 Polys / 6 Cs

9. S-R & Addict. D. Vs. Hypertension
• Genetics 50 - 60% 25 - 50%
• Relapse 40 - 60% 50 – 70%
• Initiation Alc./Drug use Diet/Activity
• Permanent Potential Same
• Due to and cause Physiologic Changes Both
• Abstinence/Meds Lifestyle
Changes/Meds
Do Not reverse disorder, Both Incurable
• ＜ 50% 1 yr. Abstin. ＜ 40% on meds &
＜ 30% LS after 1 yr.

10. Mental Health Parity and Addiction
Equity Act Oct. 2008
(implementation with ACA 2014)
• Addiction is a biologic & psychological Medical
Disorder due to anomalous neurocellular,
neuro-chemical &
neuro-functional features of vulnerable
individuals
• 10 U.S. Addiction Medicine Residency
programs launched on 7/1/12; 23 June 2014,
27 Jan. 2015, 65 by 2020 ABAM 2015

11. DSM-5 May 18, 2013
Impulse Control Disorders of DSM IV-TR
redefined as Substance-Related and
Addictive Disorders
Pathological Gambling accepted as such
Compulsive Buying?
Compulsive Sexual Behavior maybe
Internet or Compulsive Computer Use?
Others: Trichotillomania, Kleptomania,
Pyromania, Intermittent Explosive Disorder

13. Addiction Pathway
Brain Circuits & Processes
 Reward/Reinforcement (Go)Reward/Reinforcement (Go)
[I prefer Survival/Reinforcement][I prefer Survival/Reinforcement]
Hyperactivity then HypoactivityHyperactivity then Hypoactivity
 ControlControl (Stop)(Stop)
Impaired, dysfunctional orImpaired, dysfunctional or
disconnection of Go and Stopdisconnection of Go and Stop
Bill Cohen: “Overactive go, Damaged Stop & Lack ofBill Cohen: “Overactive go, Damaged Stop & Lack of
Communication between them”Communication between them”

14. Neurons in Earth’s Fossil Record: Spinal Cord to
Diencephalon to Mammalian-Meso Cortex to Neo
Cortex
Fish 500 mya
Reptiles 300 mya
Amphibians 315 mya
Mammals 220 mya
Primates 65 myaHominids 5 mya
Earth 4.5 Billion Years, Life from 4 Billion Years

15. CNS Addiction Pathway
Survival/Reinforcement Circuit
Control Circuit
GO!
STOP!
Our Brain’s Go & Stop Switch

16. Stop Switch
Go
Switch
Brains Addiction Pathway

17. Blum K. et al. (2014)

18. Brain on
Cocaine
Minutes
after
shooting
or
smoking
Courtesy of
Nora Volkow, Ph.D.

19. Cocaine affects addict’s brain
differently than a Normies brain
Glucose metabolism in Prefrontal Cortex & Cingulate Gyrus

20. Diabetes = Pancreas Beta Cell
Anomaly

22. VTA Dopamine Cells of Opiate
Addict vs. Non Addict Rat

23. Stop Switch
Go
Switch
Addiction Pathway: Go and Stop SwitchesAddiction Pathway: Go and Stop Switches

24. Last Area of Brain to Develop is
Prefrontal Cortex
Reasoning, Impulse Control, Temporal Processing, Planning, Judgment
Medial PFC = Value
Lateral PFCs = Costs
or consequences

25. Control Circuitry = Stop Switch
• Orbital Prefrontal Cortex –
Especially left ventral medial OFC
• Fasciculus Retroflexus (anterior)
• Lateral Habenula (posterior and
mesocortex terminal)
Age of first use correlation to future addiction

26. Diffusion Tensor Imaging

28. Adolescent Pot User 2-4 X more likely to
go on to other drug problems

30. Limbic Area
• Role: Drive Generation (SURVIVAL)
• Intervention: Pharmacotherapy
Acute Reinforcing Effects
Courtesy of Dr. John Hart
Prefrontal Cortex
• Role: Executive Function
• Intervention: Counseling

31. Prefrontal
Cortex
Nucleus
Accumbens
Arcuate
Nucleus Ventral
Tegmental
Area
Brain Reward Pathways
Dopamine
Opioid Peptides
Glutamate
Courtesy of Dr. John Hart, Portland, Oregon

32. Relapse Related Brain Circuits
and Processes
 Stay Stopped (Slip Decisions)Stay Stopped (Slip Decisions)
 Emotional Memory (Cravings)Emotional Memory (Cravings)
 Stress Hormone CycleStress Hormone Cycle
(Hypersensitivity)(Hypersensitivity)

33. Brain Processes of Relapse
A. Slip/Stay Stopped
Brain Anomalies

34. Right Insula Right Inferior Parietal Lobule
Similar Findings: Bando, Kenneth et al.Similar Findings: Bando, Kenneth et al.
Am. J. of Psychiatry, 168(2):183-192, 2011Am. J. of Psychiatry, 168(2):183-192, 2011
Right InsulaRight Insula
Right InferiorRight Inferior
Parietal LobuleParietal Lobule
Right MiddleRight Middle
Temporal GyrusTemporal Gyrus
Left Cauate/Left Cauate/
PutamenPutamen
Left CingulateLeft Cingulate
GyrusGyrus
Courtesy of Paulus, M.P.; Tapert, S.F.;Courtesy of Paulus, M.P.; Tapert, S.F.;
and Schuckit, M.A. l NIDA, Archives ofand Schuckit, M.A. l NIDA, Archives of
General Psychiatry, 62(7):761-8, 2005General Psychiatry, 62(7):761-8, 2005

36. Brain Processes of Relapse
B. Memories
Formation & Role
In Drug Cravings

37. Neuro-development
of Memories
Dendritic spines, bumps
or protrusions

38. Dendritic Memory Spines
• Amygdala process emotional memories,
hippocampus all other memories
• Also known as Bumps, Spikes – I like the term
memory protrusions = less triggering
• 4 to 6 sensory inputs of the same stimulus per
hour results in development of a semi-
permanent memory protrusion
• The more often a memory protrusion is
activated the larger it grows and the more
permanent it becomes

39. © Magal Mondin and Daniel Choquet, CNRS, Universite Bordeaux 2
All Addiction Memories are processed as emotional
memories via the amygdala, these are faster and
have a more powerful influence on Behavior than
hippocampal working memories

41. Courtesy of Max Planck Institute of Neurobiology

42. Meso-Limbic Reward-Reinforcement
Circuitry of the MFB
 Phase I – Endogenous/Environmental Cue or memory
triggers the Ventral Tegmental Area to release
dopamine which activates core of Nucleus Accumbens
Septi = anticipation of use ON A MISSION! If initiated
difficult to stop
 Phase II – Cues or actual use of addictive drug activates
dopamine “go” switches of lateral hypothalamus and
Nucleus Accumbens (core and shell): COMPULSION FOR
MORE!
 Phase III – Control circuitry of the prefrontal cortex is
inactivated, while the cingulate (bonding) is activated:
results in LOSS OF CONTROL, CONTINUE DESPITE
NEGATIVE CONSEQUENCES

43. Prefrontal
Cortex
Nucleus
Accumbens
Arcuate
Nucleus Ventral
Tegmental
Area
Brain’s Addiction Pathway
Dopamine
Opioid Peptides
Glutamate
Courtesy of Dr. John Hart, Portland, Oregon

44. New NIH Details on Addiction
Craving Brain Pathway
• Hippocampal memory process activates
• Lateral Septum via glutamate and this in
turn activates
• Ventral Tegmental Area (VTA) via gamma-
aminobutyric acid (GABA) that then activates
• Nucleus Accumbens Septi (“go Switch”) via
dopamine
Luo, AH, et al. Science 7/15/11

45. Brain Processes of Relapse
C. Stress Hormone
Cycle
Hypersensitivity

46. Hypersensitivity of Stress
Hormone Cycle in Addiction
1. Stress activates
hypothalamus
release of corti-
cotropin Releasing
factor (CRF)
2. CRF activates
pituitary release of
adrenocortico-
tropic hormone
(ACTH)
3.ACTH activates
kidney adrenal
glands to release
cortisol

47. “Addiction is a stress-induced defect in
midbrain’s ability to perceive pleasure”
Dr. Kevin McCauley
• CRF & ACTH are neurotransmitters as well as hormones they
modulate novelty-seeking and dopamine activity in the brain
• Severe stress increase risk-taking behaviors in all and
suppress dopamine’s ability to perceive reward, survival
reinforcement, “pleasure?” resulting in anhedonia since
• CRF & ACTH as neurotransmitters produce the unpleasant
emotional reactions associated with stress
• Cortisol usually turns off these secretions to terminate a stress
reaction but extreme stress overrules cortisol

48. Addictive drugs first release of dopamine in
the midbrain fools it as being a coping
mechanism for the relieve of stress
• Opiates & endorphins shown to also inhibit CRF & ACTH as
cortisol would naturally do
• But, withdrawal from opiates cause increase release of CRF, ACTH
and creates hypersensivity to stress that overrule cortisol’s
regulation of cycle = craving
• Cocaine directly releases the CRF and ACTH mistaken as part of or
covered by the rush, stimulant withdrawal also activates the
stress mechanism = craving
• Research: metyrapone validation (shuts off cortisol production
increasing CRF & ACTH) and CP-154,526 treatment (blocks CRF
and thus suppresses ACTH release) Heilig
and Koob 2007, Lowery et al. 2008

49. Also Neural Crux of Relapse with
Stress March 2013
VTA’s (ventral tegmental area): GABA-releasing
neurons, dopamine-releasing neurons and Kappa
opioid receptors interaction in stress. Drugs and
natural satiations release dopamine in the VTA. GABA
applies a brake to this via strengthening synapses
(known as long-term potentiation or LTP) but stress
interrupts this process leading to unabated dopamine
reinforcement. Nor-BNI blocks Kappa receptors in the
VTA and prevents stressed out rats from relapsing to
cocaine use
Graziane, Polter, Briand, Pierce, Kauer (2013), J. Neuron

50. © 2007, CNS Productions, Inc.
Fish Cat Chimpanzee Human fr. 5Ma
Old Brain = Survival (5X faster and more powerful) than Neocortex =
Control, Planning and Decision Making
Addiction is a battle between the old
primal brain and the new brain

51. Historic Evolution
of
Addiction Science

52. Dr. James Olds, McGill University
Toronto, Canada 1954
Operant Conditioning
Dr. Terry Robinson
U of Mchg. 2004
Incentive Sensitization Research Confirmation

58. Courtesy of National Institute of Drug Abuse

60. American Society of Addiction
Medicine Definition
Addiction is a primary, chronic disease
of brain reward, motivation, memory
and related circuitry
Adopted April 19, 2011
A Brain Reward Disorder
Dr. Kenneth Blum 1990

61. • is a primary, chronic disease of brain reward,
motivation, memory and related circuitry.
Dysfunction in these circuits leads to
characteristic biological, psychological, social
and spiritual manifestations. This is reflected
in an individual pathologically pursuing reward
and/or relief by substance use and other
behaviors.
– (ASAM definition, Short Version)
ADDICTION DEFINITON
American Society of
Addiction Medicine

62. National Institute on Drug Abuse
(NIDA) View of Addiction

64. Brief Review of Brain Cells and their
communication processes

65. Courtesy, Takeichi Laboratory, Nagoya, Japan

66. © 2007, CNS Production, Inc.

67. Courtesy of UC, San Diego, Goda, Y., Sailor, M., Collins, B.

69. Cell Body
Myelin Sheath
of Axon
Dendrite
Synapse
Dendritic Spine
By Age 6 100 Billion Neurons and
Development of a Quadrillion
Synapses

71. Electron Microscopy of Neurons,
Dendrites and Axons
Professor Terry Wiseth, Northland College

72. NeurotransmittersNeurotransmitters
AcetylcholineAcetylcholine Substance “P”Substance “P”
NorepinephrineNorepinephrine AnandamideAnandamide
EpinephrineEpinephrine GlycineGlycine
DopamineDopamine HistamineHistamine
EndorphinEndorphin Nitric oxideNitric oxide
EnkephalinEnkephalin Glutamic acidGlutamic acid
Serotonin (5HT)Serotonin (5HT) CortisoneCortisone
GABAGABA Aspartic AcidAspartic Acid
© 2007, CNS Productions, Inc.
Oxytocin

73. Synapse @ 50,000x Electron Microscopy
Courtesy of Thomas Deerinck,
NCMIR/Photo Researchers, Inc.
Professor Terry Wiseth,
Northland College

74. Synapse @ 50,000x Electron
Microscopy
Courtesy of Thomas Deerinck, NCMIR/Photo Researchers, Inc..

75. Drugs Mimic, Disrupt, or Block
Neurotransmitters
SOME EXAMPLES -
UPPERS: Catecholamines (Norepinephrine,
Epinephrine, Dopamine) + Serotonin and
Acetylcholine
DOWNERS: Endorphin, Enkephalin, GABA, Serotonin
PSYCHEDELICS: Serotonin, Acetylcholine, Alpha
Psychosin, Norepinephrine, Dopamine,
Anandamide & endocannabinoids

76. Taking one: Uptown, Downtown
and “Outatown”
• CNS Stimulants increase the electrical and
chemical activity of the brain (caffeine to ‘Ice’)
• CNS Depressants decrease the electrical and
chemical activity of the brain (‘booze’ to ‘benzos’ to
opioids)
• All Arounders (Psychedelics) distort and interfere
with brain perceptions to produce delusions,
illusion, hallucinations, & syn-esthesia (DXM: ‘Robo’ to
‘paka-lolo’ to Sylvia d)
• Misc: Inhalants, Anabolic Rhoids, Behaviors

80. Key Neurotransmitters Involved
With Most Addictions

81. All Addictive Substance Involve
Dopamine Activity

82. 0
50
100
150
200
0 60 120 180
Time (min)
%ofBasalDAOutput
NAc shell
Empty
Box Feeding
Di Chiara et al., Neuroscience, 1999.
FOOD
Mounts
Intromissions
Ejaculations
Fiorino and Phillips, J. Neuroscience, 1997.
Natural Rewards Elevate Dopamine
Levels
100
150
200
DAConcentration(%Baseline)
15
0
5
10
CopulationFrequency
Sample
Number
1 2 3 4 5 6 7 8
SEX
Female Present

83. Natural and Drug Reinforcers
Increase Dopamine in NAc
VTA/SN
nucleus
accumbens
frontal
cortex
Drugs of abuse increase DA in the
Nucleus Accumbens, which is believed
to trigger the neuroadaptions that
result in addiction
0
100
200
300
400
500
600
700
800
900
1000
1100
0 1 2 3 4 5 hr
AMPHETAMINE
%ofBasalRelease
0
50
100
150
200
0 60 120 180
Time (min)
%ofBasalRelease
Empty
Box Feeding
Di Chiara et al., 1997
FOOD
150
125
100
0 20 40 60 80
MARIJUANAMARIJUANA
%ofBasalRelease
Tanda, et al, Scienceb 1997
Di Chiara et al., 1997

84. 0
100
200
300
400
500
600
700
800
900
1000
1100
0 1 2 3 4 5 hr
Time After Amphetamine
%ofBasalRelease
DA
DOPAC
HVA
Accumbens AMPHETAMINE
0
100
200
300
400
0 1 2 3 4 5 hr
Time After Cocaine
%ofBasalRelease
DA
DOPAC
HVA
Accumbens
COCAINE
0
100
150
200
250
0 1 2 3 4 5hr
Time After Morphine
%ofBasalRelease
Accumbens
0.5
1.0
2.5
10
Dose (mg/kg)
MORPHINE
0
100
150
200
250
0 1 2 3 hr
Time After Nicotine
%ofBasalRelease
Accumbens
Caudate
NICOTINE
Di Chiara and Imperato, PNAS,
1988
Effects of Drugs on Dopamine Release

85. Addiction: About 9% of Pot users may become dependent,
1 in 6 who start in adolescence and 25-50% of daily users
32
15
9
17
11
8
5
23
0
5
10
15
20
25
30
35
Percent
* Nonmedical Use Source: Anthony JC et al., 1994
Estimated Prevalence of
Dependence Among Users
*
*
American Psychiatric Association’s Diagnostic ManualAmerican Psychiatric Association’s Diagnostic Manual
(DSM) has included marijuana use disorders since(DSM) has included marijuana use disorders since
1980.1980.
DSM-5 added Marijuana Withdrawal as a diagnosis.DSM-5 added Marijuana Withdrawal as a diagnosis.

86. 2012 UCSF Research Confirms Role of Endogenous Opioid
Neurotransmitters in Reward Circuitry as well as Dopamine
Beta Endorphin Met-Enkephalin

87. Also Excess Nor Epinephrine (Nor Adrenaline) and Less
Transporters in Pathological Gamblers
Confirmed: Takahashi et al.

88. Expanding Role of GABA &
Glutamate
Inhibitory Excitatory

89. Glutamate role in Addiction
Pathway confirmed Nov. 2014
Labeled neurons in rodent reward circuitry that starts in dorsal raphe with
glutamate stimulation releasing dopamine to the VTA (pictured — ventral
tegmental area). Image courtesy Dr. Marisela Morales, NIDA IRP

90. Serotonin aka 5-hydroxytryptamine also
involved with all addictions?

92. Brain Imaging:
Impact of Addiction Pathology

93. 1980s – First MRI studies of brain
development
1990s – fMRI find white matter
increases and gray matter decreases
with age
Thus, Process of Brain Development & Impact
of Addiction Pathology Revealed
BrainImaging

95. Portable fMRI Halo Systems

96. Functional Near Infrared Optical
Imaging (fNIR)

97. Addiction Pathology via
new neuroimaging techniques
Anatomical (Structure)
CT/CAT, MRI/MRI-GUI, X-Ray, dMRI,
DTI
Functional
ASL, DOI/DOT,EEG, EROS, fMRI/ Bold
fMRI, MEG, PET, SPECT, SPM, et al.
Scans

98. Multiple Brain Imaging Techniques

100. Normal Normal Normal Normal
Courtesy of Volkow, Wang, & Begleiter, et al.)Courtesy of Wang,Volkow, Panayotis & Fowler (2004)

101. Nicotine Evokes Addictive Brain
Changes With Just One Puff
Control 1 Puff 3 Puffs 1 Cigarette 3 Cigarettes MRI
3.1 hour after smoking these amounts calculated PET
Brody,Al, et al (2008) Intl J Neuropsychopharm.

102. Brain on
Cocaine
Minutes
after
shooting
or
smoking
Courtesy of
Nora Volkow, Ph.D.

103. Courtesy of Daniel Amen, M.D.

104. Courtesy of Daniel Amen, M.D.

105. Courtesy of Daniel Amen, M.D.
Marijuana Abuse

109. Brain Imaging Revealing Anomalies Of
Process Addictions: Gambling

112. © 2007, CNS Productions, Inc.© 2007, CNS Productions, Inc.

113. Internet Including Gaming and
Gambling On-Line

114. Sex Addiction

115. Romantic Passion = Love Addiction
Dr. Helen Fisher Rutgers & Dr. Lucy Brown Albert Einstein College
Brain scans of newly in love viewing photos of love vs. others show VTA
activity to NAcS to Frontal Cortex same as drug addiction. Major Symptoms of
Romantic Love: Craving for Emotional Union, Intense Thinking / Compulsion,
and Motivation to win the person that are involuntary and hard to control

116. Dopamine Depletion in All Addictions =
Endogenous Craving and Anhedonia results
in Reward Deficiency Syndrome

118. Part I Science of Addiction
Conclusion
• Addiction is not about morals, will power or
character. It’s about anomalous neurocellular,
neurochemical and neurofunctional features of
vulnerable brains that hijacks their reward and
control circuits resulting in behaviors that are
defined as Addiction – an impairment of choice
• Good news is that the brain is resilient, it’s plastic,
it has the ability to bring itself back to healthy
functionality if given the chance to.

119. A lot of information
compressed in a very
short time!
Questions?

120. Current Science of Recovery Continues
• Developments in Addiction
Treatment
• Relapse (Recrudescence)
Prevention: Promoting Long-
Term Recovery
2 Stops Remaining

121. Part II a: Developments in Addiction
Treatment
Screening, Assessment, Intervention
And Treatment Resources
NIDA: Components of Comprehensive Drug
Abuse Treatment

124. © 2007, CNS Productions, Inc.

127. Addiction still requires a
self-diagnosis for effective
treatment to commence

128. Addiction Treatment Challenges
A. Barthwell (ONDCP), UFDS, TEDS
• Awareness Gap- 76% who meet diagnostic criteria claim to
have no problems (Denial)
• Motivation Gap- Only 5% who recognize their addiction
problem will seek treatment
• Success Gap- 2% of those wanting and seeking treatment
are unable to access it within a year, but only 50% get
treatment ~on demand
• Treatment Gap- Only 1/26 who meet diagnostic criteria
access treatment annually
• Continuity Gap- Only 25%-31% who enter treatment will
complete with a + discharge
• Outcome Gap- 50% completers will remain abstinence for
at least one year

129. Assessment &
Treatment of
Substance-Related
and Addictive
Disorders

130. ScreeningScreening
• Last use of tobacco, alcohol, drugLast use of tobacco, alcohol, drug
(Are you interested in quitting?)(Are you interested in quitting?)
• Ever experimented with drugs?Ever experimented with drugs?
• CAGE-AID (CAGE)CAGE-AID (CAGE)
• Quantity & frequency of use?Quantity & frequency of use?
• Can you abstain from alcohol whileCan you abstain from alcohol while
using RX?using RX?
• S-BIRT (Screen, Brief Intervention, ReferralS-BIRT (Screen, Brief Intervention, Referral
Treatment) = 68% decrease illicit drug useTreatment) = 68% decrease illicit drug use

131. Research-Validated SUD Diagnosis and
Assessment Tools
• Addiction Severity Index (ASI)
• Michigan Alcoholism Screening Test (MAST)
B-MAST, MAST/AD, M-SAPS, SMAST-G
• DSM-IV-Tr, DSM-5, SCID-1
• CAGE-AID, SASSI-3 & -A2, CRAFFT
• 4P-Plus, TICS, PADDI
• TWEAK, DAST
• ASAM PPC-2R (Six Dimensions)
• ASSIST & NM ASSIST

132. TREATMENT CONTINUUM
 Detoxification
 Initial Abstinence
 Long-term Abstinence
 Recovery
 ASAM 4 Levels of Treatment:
4, 3.7, 3.4, 3.2, 2.5, 2, 1, 0.5, et al.

139. Addiction is a “tug of war” between the older
Meso Cortex Survival Brain and the modern
thinking Neo Cortex Brain
Fish 500 mya
Cambrian Explosion
Reptiles 300 mya
Amphibians 315 mya
Mammals 220 mya
Primates 65 myaHominids 5 mya
Earth 4.5 Billion Years, Life from 4 Billion Years

140. Remember: Both Cortical and Sub-Cortical parts of the
brain involved in Addiction
Mesocortex, Limbic System, Basal Ganglia:
Unconscious Survival Brain
Neocortex: Aware Human Brain

141. Prefrontal
Cortex
Nucleus
Accumbens
Arcuate
Nucleus Ventral
Tegmental
Area
Brain’s Addiction Pathway
Dopamine
Opioid Peptides
Glutamate
Courtesy of Dr. John Hart, Portland, Oregon

142. Limbic Area
• Role: Drive Generation (SURVIVAL)
• Intervention: Pharmacotherapy
Thus, Both the Unconscious & Conscious
Brain Require Treatment
Courtesy of Dr. John Hart
Prefrontal Cortex
• Role: Executive Function
• Intervention: Counseling

143. Clinical Treatments Targeted for Cortical
(conscious) processes of Addiction

144. Clinical Interventions: Evidenced-Based &
>100 yrs of Practiced-Based Interventions
• National Registry of Evidence-Based Program and
Practices: SAMHSA & State
• Cognitive Behavioral Therapies: Motivational
Interview/Enhancement, DBT
• Levels of Change
• Individual and/or Group Counseling (process,
therapy, education, topical, open)
• Manual Driven Curricula (e.g. Matrix)
• Self-Help Groups (12-Steps, et. al.)

145. New Paradigm of Addiction
Treatment
Addiction is a systemic and family disorder. It
impacts everyone not just the addict.
Studies now document that treatment of
addiction in isolation, without the involved
treatment of families and systems that are part
of an addicts life will result in a more frequent
return to addictive roles and behaviors following
even positive treatment outcomes

146. Recovery Coach
• Recovery Coach, Mentor
• Sober Companion, Escort, Mentor
• Recovery Support Specialist
• Family Recovery Coach
• Telephone or Virtual Recovery Coach
• Legal Support Specialist Recovery Coach
• Volunteer Peer Recovery Support Specialist

147. Trauma Informed/Focused Care
Trauma Informed Care is an organizational
structure and treatment framework that involves
understanding, recognizing, and responding to
the effects of all types of trauma. Trauma
Informed Care also emphasizes physical,
psychological and emotional safety for both
consumers and providers, and helps survivors
rebuild a sense of control and empowerment.

148. Treatments Targeted for Sub Cortical
(unconscious) Processes of Addiction
Sub Cortical Brain Structures
i.e. ~400 vaccines, genetic therapy, pharmaco-
genomics, and ~more medication treatments in
developments than any other medical

149. Maintenance pharmacotherapy, replacement
therapies, chemically assisted detoxification or
recovery; agonist mediated “anti-priming”
treatments, pharmacologic restoration of
neurohomeostasis, addiction vaccines, phar-
macogenomics and genetic treatment “reset-ting”
the addicted brain. Such terms would have been
incomprehensible or even oxy-moronic in the
recovery field just a few short years. Now,
increased understanding, Addiction Equity Act of
2008 and Affordable Health Care Act are rapidly
increasing the “medicalization” of addiction
treatment.

150. Detox: Development of Withdrawal
Management Assessment Tools
• CIWA-Ar Clinical Institute Withdrawal Assessment of
Alcohol-Revised
• COWS, Clinical Opiate Withdrawal Scale
• ACSA, Amphetamine Cessation Symptom Assessment
Scale
• BWAS, Benzodiazepine Withdrawal Assessment Scale
• WAT-1, Withdrawal Assessment Tool
• MSSA, Modified Selective Severity Assessment
Detoxification Scoring

151. Initial Abstinence: Pharmacological Cue
Extinction via naltrexone and acamprosate

152. Meds for Alcohol Treatment
• disulfiram (Antabuse®)
• naltrexone: (ReVia®, Depade ® PO or Vivitrol® IM)
• acamprosate (Campral®)
• chlordiazepoxide (Librium®) or Off-Label phenobarbital,
other benzodiazepine for short-term detox
• Off-Label: clonidine (Catapres®), lofexidine (Britlofex®)
• Off-Label Anti-Seizure meds: topiramate (Topamax®),
gabapentin (Neurontin®)
• Misc. Off-Label: ondansetron (Zofran®), flumazenil in
-Prometa, baclofen (Lioresal®), nalmefene (Revex®, Selincro®)

153. Meds for Nicotine Treatment
• varenicline (Chantix®)
• bupropion (Zyban®, Wellbutrin®)
• Nicotine Replacement Therapies (NRT):
gum (Nicorette®), patch (OTC-Nicotrol®,
Nicoderm CQ®; Rx-ProStep®, Habitrol®), spray
(Nicotrol NS®
), inhaler (Nicotrol®
aerosol), and
lozenge (Commit®
)
• Off-Label: nortriptyline, clonidine

154. Tobacco Use Ban at Addiction
Treatment Programs
• Late 1980’s Haight Ashbury Substance Abuse
Treatment Programs
• 2008 New York State and then New Jersey
State addiction treatment programs
• Addictions Recovery Center, Medford, Oregon
January 1, 2012
• State of Oregon July 1, 2012.
Client (inc. non-users), Staff, Administration
(outcomes), and even community conflicts

155. Negative Impact on Treatment
Completions Clark-Hammon & Gregoire (2011)
• Total % of treatment drop-out nearly doubled
from 30% before the ban to 58% after
• Smoking client drop-outs doubled from 20% prior
to 42% after the ban
• Non-Smoking client drop-outs tripled from 7%
prior to 22% after (chaos of enforcement)
• But overall health of those who did complete
treatment should be much improved

156. Smoking Inhibits Success of Alcohol
Abuse Treatment
• 2014 Study of >21,000 adults in 263 New
York Outpatient SAT Clinics
• Smokers had shorter treatment durations
and less likely to achieve treatment goals
• Smoker/Drinkers: ↑ unemployment, CJS
involvement, mental illness, other drugs of
abuse and ↓ HS diploma or GED
• < 20% US smoke (<15% ) but 67% and
61% of seeking alcohol treatment smoke
Walitzer, KS et al. (2015)

157. Other Considerations
• Increases Client Trauma in an era of
trauma-informed care
• Inflames staff policing and punitive
practices
• Causes clients to go underground and
perpetuates their “criminal” thinking
• Staff and Clients view of rights being
violated
• Overall health benefits great for all but at
what costs?

158. Meds for Opioid Treatment
• buprenorphine (Suboxone®, Zubsolv®)
• naltrexone (Revia®, Depade®, & Vivitrol®)
• methadone
• levo-alpha-acetyl-methadol (LAAM)
• Off-Label: clonidine, lofexidine
• Off-Label: Rapid Opioid Detoxification
(naloxone or naltrexone with midazolam, lorazepam,
clonidine, anesthetics, et al.)
• Illicit in U.S.: Ibogaine

159. Buprenorphine (Suboxone) Ceiling Effect

161. Jackson County Rx OD deathsCourtesy
of Dr. Jim Shames

162. Suboxone more Rxed than methadone

163. Centers for Disease Control and
Prevention (CDC) 7/3/12
Steep Rise in Methadone OD deaths in 2000s
Peaked out in 2007 and now falling
Still, methadone currently accounts for almost
1/3 of U.S. Rx medication deaths
In 2011 methadone was only 2% of all pain
prescriptions yet responsible for more than
30% of Rx pain medication deaths

164. The Under – Over Medication
Pendulum
Anxiolytics – benzodiazepines
Treatment of ADD/ ADHD – analeptics
Especially Analgesics – opiate and opioids
morphine, methadone, Oxycontin, Vicodan
and now Zohydro/Hysingla advocacy

165. Current Epidemic of Iatrogenic of Rx
Opioid Pain Medication Addiction
and OD Deaths
In 2010 U.S. Prescription Drug Deaths
(primarily opioid pain medications) were
Greater than Auto Accident Deaths!
Methadone represented 30% of these deaths
in 2010 yet only amounted to only 2% of all
pain medications prescribed

166. Center for Disease Control Evaluation of Rx
Drug Abuse Problem
*Unintended Rx drug OD death every 19 minutes in
2007
*Each Rx opioid OD death = 9 detox admissions, 35 ER
visits, 161 abusers/addicts, & 461 reports of
nonmedical use of Rx opioids
*9 million U.S. long-term medical Rx opioids users and 5
million annually report nonmedical use
*Pharmacy U.S. distribution of Rx opioids rose 600%
from morphine equivalent of 96 mg. in 1997 to 700
mg. per capita in 2007

167. Rates of prescription painkiller sales, deaths
and substance abuse treatment admissions
(1999-2010)

169. Amount of prescription painkillers sold by
state per 10,000 people (2010)

170. Drug overdose death rates by state per
100,000 people (2008)

171. June 2012 US Senate Caucus on
International Narcotics Control
• Rx drugs now second most common form of
drug abuse in the U.S.
• Now responsible for most OD deaths, greater
than heroin and cocaine combined
• Violent pharmacy robberies increased 82%
between 2006 and 2011
• NSDUH data indicates 70% or Rx drugs were
supplied by friends or relatives

172. July 2013 CDC Report: More Rx med
death than car crash death in U.S.
• 1999-2010 Rx Opioid OD death increased 400%, in
women, 265% in men. 18 women deaths every day!
• Rx meds (esp. Oxycontin & Vicodin) comprised 34% of
suicide deaths in women and 8% in men
• >200,000 women ER visits were due to misuse or abuse of
these drugs, ~one every three minutes
• Rx Opioid OD deaths were greater than 4 times as many
cocaine and heroin deaths in women
• Dr. Thomas Frieden, CDC Director now estimates 42
women deaths each day from Rx Opioid ODs

173. Opioid Pain Medications
(downers)
In 2010 U.S. Prescription Drug Deaths
(primarily opioid pain medications) were
Greater than Auto Accident Deaths!
Methadone represented 30% of these
deaths in 2010 yet only amounted to only
2% of all pain medications prescribed

174. Some Unethical, Unwise, and
Over-Prescribing of Opioids
Many horror stories and tabloid reports
especially when a public figure is
involved or overdoses (e.g. This dog
X-ray used in a sting to get pain meds)
But, Most diverted opioid and other prescription
drugs are obtained from friends or family
members

175. Also many horror stories of overzealous
restriction of such medications from
appropriately medical uses – Pseudo
Addictions?
Many states have regulations recognizing
pain to be the Fifth Vital Sign of medical
treatment and recognize the right of
patients to appropriate assessment and
management of pain

176. Pseudoaddiction
• Operationally defined as aberrant drug-related
behaviors that make patients with chronic pain
look like addicts.
• These behaviors stop if opioid doses are increased
and pain improves. (Weissman and Haddox, 1989)
• This indicates that the aberrant drug-related
behaviors were actually a search for relief
• Little data on the subject – Only a single human
report as of 2014, but evidence in rats

177. Types of Pain
(Chronic Pain = lasts 3-6
months or longer)
• Nociceptive Pain (sprains, bone fractures, burns,
bruises)-special nerve ending which heal with time
• Neuropathic Pain (shingles, Diabetic Neuropathy
neuralgia, phantom limb pain, Carpal Tunnel
Syndrome /CTS, peripheral neuropathy)-nervous system
dysfunction pain
• Mixed Category Pain (migraine headaches)-complex
mixture of nociceptive and neuropathic
• Central Pain-caused by dysfunction of nervous system
such as Fibromyalgia
• Emotional Pain (loss, relationship, humiliation,
disappointments, exclusion, fears, psychological
trauma)

179. Physical Pain Registration in the
Anterior Cingulate Cortex (ACC)
Pujol, J et al (2009), PLoS ONE

180. Signatures of Various Chronic Syndromes
Chronic Back
Pain
Complex Regional
Pain Syndrome
Osteoarthritis
2011

181. fMRI Reveal Emotional Pain
Signature Pathway
Prefrontal Cortex to Nucleus Accumbens and amygdala
Wager, Tor (2013), NEJM

182. Neurologic Pain Signature
Wager, Tor (2013),
NEJM

183. fMRI Scans image pain signature,
measure intensity and demonstrate
when relief occurs
Wager, Tor (2013), NEJM

184. Tools for Assessing Pain should
also assess stress
_•______•_______•______•______•_
Low Stress Mild Stress Stressed Out

185. American Chronic Pain Ascn. Tools for
management of Chronic Pain
QoL management not elimination of pain is key
Ability Chart – 11 self-evaluation domains
on 11 point Likert Scale:
Pain Level Personal Care
Getting Out of Bed Daily Activity
Climbing Stairs Working
Descending Stairs Leisure Activities
Getting Out of a Chair Quality of Life
Walking ACPA Rocklin, CA 800-533-3321

186. NIH 9/13/15 Pain White Paper
• Little to No evidence for opioid effectiveness in
long-term chronic pain
• Yet, Rx for opioid drugs have more than tripled in
past 20 yrs. (219 million Rxs in 2011)
• U.S. Rx Drug Abuse Epidemic >16,000 Rx Opioid
Deaths in 2012
• U.S. 4.6% of World Population Consumes 80% of
World’s Opioid Drugs
• Also, U.S. heroin deaths increased 39% in 2013
CDC 2013 Mortality Data Jan. 2015
Annals of Internal Medicine 2015

187. Chronic use of opioids for pain
management: Expanding Concerns
• Hyperalgesia = increasing pain due to PAF
activation of chemokines (i.e. cytokines) release
with opioid treatment of nociceptive pain that
will disappear with healing
• Neuropathic Pain or Hyperpathia = increasing
pain due to peripheral nerve and spinal dorsal
horn sensitization that will persist after the pain
stimulus is healed

188. Uppers, Downers, All Arounders 8th
Ed., in publication

189. Opiate Hyperalgesia
Analgesic response with tolerance:
Pain continues to overcome increased
doses of opiates
Courtesy of Andrew Mendenhall M.D.

190. Chronic use of opioids for pain
management: Expanding Concerns
• Hyperkatifeia = hypersensitivity or increased
emotional pain/distress with chronic opioid
treatment
• Allodynia = development of painful response to
normally innocuous stimulus such as light touch on
the skin or warm or cool temperature
• Opioid Addiction = development of tolerance, tissue
dependence, withdrawal and psychological
dependence

191. Delta Opioid Receptor
Medication developments targeting this
receptor has been shown to effectively
relieve allodynia without causing opioid
addiction
Rita Bardoni, et al. (2014) Neuron
81(6):1312–1327, 19 March 2014

193. Tools for Assessing
Addiction Risk

195. Opioid Misuse
Behaviors to Watch for
More Suggestive of
Abuse/Addiction
• Selling Prescription drugs
• Stealing drugs from others
• Repeated dose escalation
• Repeated visits to the E.R.
• Repeated loss of
medication or request for
early refill
Less Suggestive of
Abuse/Addiction
• Openly acquiring pain meds
from other doctors
• Drug hoarding during
periods of reduced
symptoms
• Aggressive complaining
about need for more pain
meds.
• Reluctance to try alternative
treatments

196. Alternative Medications for Pain
• Nonsteroidal anti-inflammatory drugs (e.g. ibuprofen,
Aleve, Clinoril)
• Acetaminophen
• NE RI Antidepressants (e.g. Cymbalta, Effexor)
• Anticonvulsants (e.g. Topamax, Neurontin, Tegretol)
• Steroids (e.g. Prednisone, Decadron, hydrocortisone)
• Muscle relaxants (e.g. Flexeril, Robaxin, Zanaflex, Baclofen,
Skelaxin)
• Topical Anesthetic Gels (Pluronic Lecithin Organogel –
PLO)
• Cannabidiol (CBD) in marijuana “Charlotte’s Web”

197. Complementary and Alternative
Medical Treatments (CAM)
• Acupuncture, Chi Kung, Ayurveda
• Transcutaneous Elec. Nerve Stimulation (TENS)
• Psychotherapy for Stress or Depression
• Relaxation Tx., Yoga, Reiki, Pilates,Meditation
• Hypnosis, Guided Imagery, Physical Therapy
• Music Therapy, Aromatherapy, Food/Nutrition
• Biofeedback, Hydro-, Oxygen-, Magnet-Therapy
• Chiropractor, Massage, Somatics, Exercise
• Puzzles (Sudoku, Crosswords, Etc.)
Pohl, Mel (2011), A Day Without Pain

198. Meds for Stimulant Treatment
Note: None FDA Approved so all are Off-Label
• Antidepressants: SSRI, TCA, bupropion
• MAOI-B: selegiline
• Neuroleptics: resperidone, olanzapine
• Sedatives: buspirone, lorazepam
• Dopaminergic: bromocriptine, amantadine
• Anti-seizures: topiramate, carbamazepine
• Amino Acids: tyrosine, phenylalanine
• Misc.: naltrexone, disulfiram, modafinil, ALKS-
33

199. Meds for Sedative-Hypnotics
Note: None FDA Approved so all are Off-Label
• Usually cross-dependent medication is used
and slowly tapered to detox
• Anti-seizure medications: phenobarbital +
phenytoin or carbamazepine or gabapentin
• flumazenil post detox to block cravings
• SSRI, TCA, or buspirone for anxiety and/or
restlessness

200. MARIJUANA ADDICTION
• 9-10% of users will meet diagnostic criteria
for cannabis use disorder 2013
• Cannabis is the most commonly identified
substance used by those admitted to
substance abuse treatment facilities in 2013
• 335,833 (18.4%) of those treated for addiction
problems in 2010 list marijuana as their
primary drug of choice TEDS, N-SSATS 2012

201. Cannabis-Related Disorders
Tolerance, Dependence, Withdrawal
Diagnostic Statistical Manual of Mental
Disorder 5th
Edition (DSM-5):
• Cannabis Use Disorder
• Cannabis Intoxication
• Cannabis Withdrawal
• Other Cannabis-induced Disorders
• Unspecified Cannabis-Related Disorders

202. Cannabis Use Disorder
Diagnostic Criteria DSM-5
1. larger amounts and longer than intended
2. Inability to decrease or control use
3. Excessive time to get, use, and recover
4. Cravings or urge to use
5. Failure to fulfill work, school, home roles
6. Continued despite negative consequences
7. Important activities ceased or reduced
8. Continued in physically hazardous situations

203. Diagnostic Criteria Continued
9. Continued despite physical/psychological
problems
10. Tolerance: amount needed to get desired↑
effects or decreased effects from same
amount of cannabis consumed
11. Occurrence of withdrawal or use to relieve or
avoid withdrawal
Mild = 2-3 of symptoms of criteria
Moderate = 4-5
Severe = 6 or more

204. Marijuana Tolerance
• Rapid development to most marijuana
effects
• Some Cross Tolerance to alcohol but not
with other drugs of abuse

205. Tissue Dependence
• Seen with daily use of 2-3 “joints” over
several weeks (500mg ave. X 15% = 75 mg.
• Classic loss of control, compulsive use,
cravings and continued use despite
development of negative consequences
• Abstinence induces physical withdrawal
syndrome
• Cross Dependence unclear but use often
occurs in combination with nicotine, alcohol
and other addictive substances

206. Marijuana Withdrawal Syndrome
Symptoms occur within 8 hours of abstinence
but can be delayed up to 72 hours. Usually
peak in severity on day 10 and may last for up
to 45 days or longer.
Symptoms consist of: irritability, anger, anxiety,
restlessness, nightmares/sleep disturbances
(REM rebound), headaches, depressed mood,
craving, decreased appetite, sweating,chills,
pain, mild tremors (“cold dog shakes”)

207. Cannabis Withdrawal DSM-5
Within ~a week after cessation: 3 or more of
the following after a few months of heavy use:
1.Irritability, anger, or aggression
2.Nervousness or anxiety
3.Sleep difficulties (insomnia, disturbing dreams -
REM rebound from suppression)
4.Decreased appetite or weight loss
5.Restlessness
6.Depressed Mood

208. Cannabis Withdrawal DSM-5
7. Plus at least one of the following physical symptoms
causing significant discomfort:
• Abdominal Pain
• Shakiness/Tremors (“cold dog shakes”)
• Sweating
• Fever
• Chills
• Or Headaches
Most Signs and Symptoms 1 - 7 last for 1 to 2 weeks,
Sleep Disturbances can last for more than 30 days.

209. Meds for Marijuana Addiction
Note: None FDA Approved so all are Off-Label
• kynurenic acid
• N-Acetylcysteine dietary suppliment
• bupropion,
• buspirone
• divalproex,
• naltrexone,
• lithium,
• antidepressants, and
• THC replacement

210. Developing Medications: N-Acetylcysteine
for Marijuana-Dependent Adolescents
Proportion of Negative Urine Cannabinoid Tests Over Time Among
Cannabis-Dependent Adolescents
Gray KM et al., AJP June 15, 2012.

211. Plethora of Medication Strategies for
Addiction Treatment
• 400 Vaccines and New Antagonists
• New Replacement Agonists (GHB)
• Partial Agonist/Antagonist (cyclazocine)
• Anti-Craving medications (nalmefene, nor-BNI)
• Metabolism modulators (BChE)
• Dopamine modulators (amantadine)
• Amino Acid supplements (Synapta Gen X)
• Ca & Na channel blockers (nimodipine, riluzole)

212. Treatment Works!
Kibou is the Japanese Kanji (calligraphy) meaning
hope. It is comprised of Ki = hope and Bou = wish.
Combined it symbolizes a good sign to overcome
difficult situations or failures.
Addiction is one of the most treatable and manageable
of all chronic, persistent medical disorders with
positive treatment outcomes that favorably compare
with the treatment of diabetes, hypertension, asthma,
et al. chronic, persistent illnesses.
Relapse is prevalent in the treatment of all chronic
medical disorders. Relapse rates after addiction
treatment also compare favorably with treatment of
other illnesses.
Kibou

213. RECOVERY
The Resilient Brain
8-10 Months Rigorous Uninterrupted
Treatment for Reasonable Outcomes
Implies time needed for brain to become
functional
Takes up to 2 years for greater functioning
to return

214. Courtesy of Nora Volkow (Volkow, Hitzmann, Wong, et al 1992

215. Courtesy of Nora Volkow, et al. Journal of Neuroscience, 21, 9414-9418, 2001

216. Dopamine Transporter Binding (DAT)
Recovery in Meth Addiction
Volkow et al. J. of Neuroscience 2001

217. Alcohol Brain Resiliency
Intoxication Sober: 30 days

220. Dr. Ken Blum’s patented:
Synapta GenX, KB220Z
Neuronutrient complex “normalization” of caudate, accumbens
and putamen regions of heroin addicts demonstrated by fMRI
Scan

221. NIDA’s 13 Principles of Effective
Treatment: A Research-Based Guide

222. • Complex but treatable disease affecting brain
function and behavior +/-
• No single treatment is appropriate for all +
• Must be readily available -
• Attends to the multiple needs of individuals ~
• Crucial to remain in treatment for adequate
period of time -
• Individual, group and other evidence-based
behavioral therapies should be employed +
• Medications combined with counseling and
behavioral therapies are important -

223. • Service plans and treatment to be assessed
continually and modified as needed +
• Evaluate & address mental health and other co-
occurring disorders for best outcomes -
• Medically assisted detox is only a first step and has
little impact on long-term outcomes -
• Treatment does not need to be voluntary to be
effective + (by default)
• Rigorous monitoring throughout treatment for
drug use may help reduce relapses -
• Disease assessment (i.e. HIV, HCV, HBV, TB) and Risk-
Reduction Education a must ~+

224. Elements of Successful Addiction
Treatment Programs
Human Intervention Motivation Study
(HIMS) of American Airlines and United
Airlines Impaired Pilots Treatment
Programs Document 87%-95% Success
Physician Health Programs PHP (i.e.
University of Florida) enjoy 90%-97%
Success
[‘Recovery Capital’ may be the major factor]

225. Prevalence of Physician Substance
Use Disorder
• 10% - 15% Lifetime prevalence (similar to
population at large)
• Ratio – Drugs to Alcohol a bit higher than
general population but alcohol is still most
common substance abused by physicians
• Overrepresented: Anesthesiology (2.5 to 1), Emergency
Medicine, Psychiatry, and Family Practice
• Underrepresented: Pediatrics, Surgery, Pathology
Anthony JC. Prevalence of substance use among US physicians. JAMA 1992; 11:268(18):2518.
Brewster JM. Prevalence of alcohol and other drug problems among physicians. JAMA 1986; 255: 1913-1920.
Talbott GD. Prevalence of alcohol and other drug problems among physicians. JAMA 1987; 21:2927-2930.
Flaherty JA, Richman JA. Substance Use and Addiction Among Medical Students, Residents, and Physicians: Recent Advances in
Addictive Disorders. Psychiatric Clinics of North America. 1993; 16: (1), 189-195.

226. PHP Intensity
• 5 yr. Contingency Contracting with worksite
monitoring
• 1-2 yrs. Weekly Group Therapy
• Individual Psychotherapy
• 12-Step Participation strongly encouraged
• Random UDS weekly for first year than down to
about 1-2/month for final 5th
year
• Recovery-enhancing practice modifications, e.g.,
shift in specialty, prescribing restrictions, altered
work setting or work schedule

227. 10 Elements of Successful
Addiction Treatment Programs
Dr. Kevin T. McCauley @ CAADE 4/15/11
1) Start with Minimum 90 day Residential Treatment
2) Transition to Immediate Aftercare Program
3) Ensure Sober-Living Environment Continuum
(Recovery Oriented System of Care)
4) Mandated 90/90 Contract = 90 12-Step Meetings in 90
days
5) Automatic Plan Established for Any Slips with goal of
making each a learning opportunity

228. 10 Elements of Successful
Addiction Treatment Programs
Continued
6) Increased Drug Testing, both UA and breathalyzer
daily, even use of remote continual alcohol meter
7) Determine Rapid or Gradual Return to Duty
8) Addictionologist a Must! Monitors Treatment Intensely
also a professional case manager
9) Psychoactive Medication Only Via Established Protocols
10) Established “Fun in Recovery” Activities

229. Recovery
• Continued Abstinence
• Discovery of Natural Highs
• Recovery of neurotransmitters and
of natural brain functions
• Positive lifestyles and quality of
life enhancements
• Remember: Not an Event but a Process
One does not cure addiction, you treat it and manage it like any
other chronic persistent medical disorder

230. Treatment Works!Treatment Works!
• 3 to 5 Yrs. Continued sobriety = 50% (1yr 80%)
• Decrease Crime = 75%
• $7-$12 Savings for every $1 Spent
• Positive results from 6-8 mo. Treatment
• Coerced treatment better than voluntary
• Decreased Psychiatric (40%),
Family/Social (50-60%), Medical (15-20%),
Employment Problems (15-20%)
• Culturally consistent better than generic treatments
Belenko, et al. 2005

231. • Good News!
Recovery Works and the brain is resilient!
• Not so Good News
It takes time, several months to years
to just become functional, and
a bit more to enjoy life again
• Addiction Pathways
Shrink with Disuse and new alternate pathways
become established (“Extinction”) but addicted
neurons are permanent and Recovery is a Life-
Long Process!

232. Conclusions
◆ Addiction treatment
results in miraculous
outcomes for those
who commit to and
maintain continuous
recovery efforts.
◆ Developments in treatments of
addiction continues to improve outcomes
that improve lives and health for all.
Me at Series End

233. Last Section of Current Science
Recovery
End of this exhausting
Journey is in sight

234. Preventing Recrudescence (relapse),
Promoting Long-Term Sobriety
Part II b:

235. Addiciton Relapse Associations
• Stigma by both addicts & “normies”
• Great shame, guilt and hopelessness in both
addicts and their families
• Progression of disorder, each successive event
results in worse consequences
• Relapse is a feature of all chronic persistent
disorders: annually 40-50% of those in treatment
for Diabetes, Hypertension or Asthma
experience relapses
McLellan AT, O’Brien CP, Lewis D, et al. JAMA 284, 2000.

236. Slip and Relapse
Slip = momentary, short-lived, isolated and
limited use of addictive substance or
practice of compulsive behaviors after a
period of abstinence (Slide?)
Relapse = return to persistent and
compulsive drug use or behavioral practice
after a period of abstinence
The frequency that a single use of drug or
addictive behavior (Slip) results in a Relapse
of a recovering addict is 95%

237. Relapse Related Brain Circuits
and Processes
 Stay Stopped (Slip Decisions)Stay Stopped (Slip Decisions)
 Emotional Memory (Cravings)Emotional Memory (Cravings)
 Stress Hormone CycleStress Hormone Cycle
(Hypersensitivity)(Hypersensitivity)

238. Brain Processes of Relapse
A. Slip/Stay Stopped
Brain Anomalies

239. Right Insula Right Inferior Parietal Lobule
Similar Findings: Bando, Kenneth et al.Similar Findings: Bando, Kenneth et al.
Am. J. of Psychiatry, 168(2):183-192, 2011Am. J. of Psychiatry, 168(2):183-192, 2011
Right InsulaRight Insula
Right InferiorRight Inferior
Parietal LobuleParietal Lobule
Right MiddleRight Middle
Temporal GyrusTemporal Gyrus
Left Cauate/Left Cauate/
PutamenPutamen
Left CingulateLeft Cingulate
GyrusGyrus
Courtesy of Paulus, M.P.; Tapert, S.F.;Courtesy of Paulus, M.P.; Tapert, S.F.;
and Schuckit, M.A. l NIDA, Archives ofand Schuckit, M.A. l NIDA, Archives of
General Psychiatry, 62(7), 2005General Psychiatry, 62(7), 2005

241. Brain Processes of Relapse
B. Memories
Formation & Role
In Drug Cravings

242. Neuro-development
of Memories
Dendritic spines, bumps
or protrusions

243. Dendritic Memory Spines
• Amygdala process emotional memories,
hippocampus all other memories
• Also known as Bumps, Spikes – I like the term
memory protrusions = less triggering
• 4 to 6 sensory inputs of the same stimulus per
hour results in development of a semi-
permanent memory protrusion
• The more often a memory protrusion is
activated the larger it grows and the more
permanent it becomes

244. © Magal Mondin and Daniel Choquet, CNRS, Universite Bordeaux 2
All Addiction Memories are processed as emotional
memories via the amygdala, these are faster and
have a more powerful influence on Behavior than
hippocampal regular memories

246. Courtesy of Max Planck Institute of Neurobiology

247. Meso-Limbic Reward-Reinforcement
Circuitry of the MFB
 Phase I – Endogenous/Environmental Cue or memory
triggers the Ventral Tegmental Area to release
dopamine which activates core of Nucleus Accumbens
Septi = anticipation of use ON A MISSION! If initiated
difficult to stop
 Phase II – Cues or actual use of addictive drug activates
dopamine “go” switches of lateral hypothalamus and
Nucleus Accumbens (core and shell): COMPULSION FOR
MORE!
 Phase III – Control circuitry of the prefrontal cortex is
disrupted, is inactivated and releasing glutamate: results
in LOSS OF CONTROL, CONTINUE DESPITE NEGATIVE
CONSEQUENCES

248. New NIH Details on Addiction
Craving Brain Pathway
• Hippocampal memory process activates
• Lateral Septum via glutamate and this in
turn activates
• Ventral Tegmental Area (VTA) via gamma-
aminobutyric acid (GABA) that then activates
• Nucleus Accumbens Septi (“go Switch”) via
dopamine
Luo, AH, et al. Science 7/15/11

249. CNS Addiction Pathway
Survival/Reinforcement Circuit
Control Circuit

250. Stop Switch
Go
Switch
Brains Addiction Pathway

251. © 2007, CNS Productions, Inc.
Fish Cat Chimpanzee Human fr. 5Ma
Old Brain = Survival (5X faster and more powerful) than Neocortex =
Control, Planning and Decision Making
Addiction is a battle between the old
primal brain and the new brain

252. Brain Processes of Relapse
C. Stress Hormone
Cycle
Hypersensitivity

253. Hypersensitivity of Stress
Hormone Cycle in Addiction
1. Stress activates
hypothalamus
release of corti-
cotropin Releasing
factor (CRF)
2. CRF activates
pituitary release of
adrenocortico-
tropic hormone
(ACTH)
3.ACTH activates
kidney adrenal
glands to release
cortisol

254. “Addiction is a stress-induced defect in
midbrain’s ability to perceive pleasure”
Dr. Kevin McCauley
• CRF & ACTH are neurotransmitters as well as hormones they
modulate novelty-seeking and dopamine activity in the brain
• Severe stress increase risk-taking behaviors in all and
suppress dopamine’s ability to perceive reward, survival
reinforcement, “pleasure?” resulting in anhedonia since
• CRF & ACTH as neurotransmitters produce the unpleasant
emotional reactions associated with stress
• Cortisol usually turns off these secretions to terminate a stress
reaction but extreme stress overrules cortisol

255. Addictive drugs first release of dopamine in
the midbrain fools it as being a coping
mechanism for the relieve of stress
• Opiates & endorphins shown to also inhibit CRF & ACTH as
cortisol would naturally do
• But, withdrawal from opiates cause increase release of CRF, ACTH
and creates hypersensivity to stress that overrule cortisol’s
regulation of cycle = craving
• Cocaine directly releases the CRF and ACTH mistaken as part of or
covered by the rush, stimulant withdrawal also activates the
stress mechanism = craving
• Research: metyrapone validation (shuts off cortisol production
increasing CRF & ACTH) and CP-154,526 treatment (blocks CRF
and thus suppresses ACTH release) Heilig
and Koob 2007, Lowery et al. 2008

256. Also Neural Crux of Relapse with
Stress March 2013
VTA’s (ventral tegmental area): GABA-releasing
neurons, dopamine-releasing neurons and Kappa
opioid receptors interaction in stress. Drugs and
natural satiations release dopamine in the VTA. GABA
applies a brake to this via strengthening synapses
(known as long-term potentiation or LTP) but stress
interrupts this process leading to unabated dopamine
reinforcement. Nor-BNI blocks Kappa receptors in the
VTA and prevents stressed out rats from relapsing to
cocaine use
Graziane, Polter, Briand, Pierce, Kauer (2013), J. Neuron

257. Challenges to Maintenance of
Continued Abstinence
• Cognitive Impairment (30-80%)
• Endogenous Craving (Allostasis)
• Environmental Triggers or Cues
• Post Acute Withdrawal Symptoms
(PAWS)
• Unaddressed Physical and/or Mental
Health Treatment Needs

258. 1. 30%-80% Cognitive
Impairment During Addictive
Behavior and in Early Recovery

259. Cognitive Impairment
11.3% of Limbic system of which
7.8% of Hippocampus plus
24% of dopamine transporters
• Attention, memory, understanding problems
• Word meaning, problem solving, Stroop
paradigm
• Inflexibility, abstract thinking, judgment
• Temporal processing: planning, processing
goals, delayed discounting

260. Brain Imaging:
Impact of Addiction Pathology

261. Multiple Brain Imaging Techniques

262. Brain on
Cocaine
Minutes
after
shooting
or
smoking
Courtesy of
Nora Volkow, Ph.D.

264. Courtesy of Daniel Amen, M.D.

266. Courtesy of Daniel Amen, M.D.
Marijuana Abuse

267. SPECT Scan: Opioid Allostasis

268. Nicotine Evokes Addictive Brain
Changes With Just One Puff
Brody,Al, et al (2008) Intl J Neuropsychopharm.

269. Brain Imaging Revealing Anomalies Of
Process Addictions: Gambling

270. Internet Including Gaming and
Gambling On-Line

271. Sex Addiction

272. Right Insula Right Inferior Parietal Lobule
Similar Findings: Bando, Kenneth et al.Similar Findings: Bando, Kenneth et al.
Am. J. of Psychiatry, 168(2):183-192, 2011Am. J. of Psychiatry, 168(2):183-192, 2011
Right InsulaRight Insula
Right InferiorRight Inferior
Parietal LobuleParietal Lobule
Right MiddleRight Middle
Temporal GyrusTemporal Gyrus
Left Caudate/Left Caudate/
PutamenPutamen
Left CingulateLeft Cingulate
GyrusGyrus
Courtesy of Paulus, M.P.; Tapert, S.F.;Courtesy of Paulus, M.P.; Tapert, S.F.;
and Schuckit, M.A. l NIDA, Archives ofand Schuckit, M.A. l NIDA, Archives of
General Psychiatry, 62(7), 2005General Psychiatry, 62(7), 2005

273. 2. Endogenous or Intrapersonal
Addiction Cravings
via Neural-Physiological
Allostasis

274. ENDOGENOUS CRAVING
Analogous to diabetes, hypothyroidism, et. al.,
an allostasis develops with continued use of an
addictive substance. When abstinence is initiated,
the brain craves the substance in an effort to
maintain its imbalanced state through a variety of
mechanisms: amygdala via emotional memories,
attachment and bonding via the cingulate gyrus
facilitated by delta fosB transcriptase and hypo-
functioning of PFC CK Himmelsbach1941, Inaba & Cohen
1986, Fredrick Von Stieff 2011

275. Brief Review:
Brain Cells and their
communication processes

276. Neuron Homeostasis: Brain in Dynamic
Equilibrium
Axon Terminal
Secondary Terminal
Auto Receptors on Axon
Synaptic Vesicles
Axonal Transport
Dendrite Receptors
Neurotransmitters
Dendrite

277. Courtesy, Takeichi Laboratory, Nagoya, Japan

279. Cell Body
Myelin Sheath
of Axon
Dendrite
Synapse
Dendritic Spine
By Age 6 100 Billion Neurons and
Development of a Quadrillion
Synapses

280. Electron Microscopy of Neurons,
Dendrites and Axons
Professor Terry Wiseth, Northland College

282. Psychoactive Drugs Affect
Perception, Mood, and States of
Consciousness by mimicking or
Disrupting the Natural Chemistry of
the Brain
Expanded Definition = Any Behaviors (e.g.
Gambling) that Alter Moods and Affect the
Brain’s Addiction Circuitries and Pathways

283. NeurotransmittersNeurotransmitters
AcetylcholineAcetylcholine Substance “P”Substance “P”
NorepinephrineNorepinephrine AnandamideAnandamide
EpinephrineEpinephrine GlycineGlycine
DopamineDopamine HistamineHistamine
EndorphinEndorphin Nitric oxideNitric oxide
EnkephalinEnkephalin Glutamic acidGlutamic acid
Serotonin (5HT)Serotonin (5HT) CortisoneCortisone
GABAGABA Aspartic AcidAspartic Acid
© 2007, CNS Productions, Inc.
Oxytocin

284. Synapse @ 50,000x Electron
Microscopy
Courtesy of Thomas Deerinck, NCMIR/Photo Researchers, Inc..

285. Synapse @ 50,000x Electron Microscopy
Courtesy of Thomas Deerinck, NCMIR/Photo
Researchers, Inc.
Professor Terry Wiseth,
Northland College

286. Drugs Mimic, Disrupt, or Block
Neurotransmitters
SOME EXAMPLES -
UPPERS: Catecholamines (Norepinephrine,
Epinephrine, Dopamine) + Serotonin and
Acetylcholine
DOWNERS: Endorphin, Enkephalin, GABA, Serotonin
PSYCHEDELICS: Serotonin, Acetylcholine, Alpha
Psychosin, Norepinephrine, Dopamine,
Anandamide & endocannabinoids

287. Taking one: Uptown, Downtown
and “Outatown”
• CNS Stimulants increase the electrical and
chemical activity of the brain (caffeine to ‘Ice’)
• CNS Depressants decrease the electrical and
chemical activity of the brain (‘booze’ to ‘benzos’ to
opioids)
• All Arounders (Psychedelics) distort and interfere
with brain perceptions to produce delusions,
illusion, hallucinations, & syn-esthesia (DXM: ‘Robo’
to ‘paka-lolo’ to Sylvia d)
• Misc: Inhalants, Anabolic Rhoids, Behaviors

288. Key Neurotransmitters Involved
With Most Addictions

289. All Addictive Substance Involve
Dopamine Activity

290. 2012 UCSF Research Confirms Role of Endogenous Opioid
Neurotransmitters in Reward Circuitry as well as Dopamine
Beta Endorphin Met-Enkephalin

291. Also Excess Nor Epinephrine (Nor Adrenaline) and Less
Transporters in Pathological Gamblers

292. Expanding Role of GABA &
Glutamate
Inhibitory Excitatory

293. Serotonin aka 5-hydroxytryptamine also
involved with all addictions?

294. Dopamine Depletion in Addiction =
Endogenous Craving and Anhedonia

295. Normal Normal Normal Normal
Courtesy of Volkow, Wang, & Begleiter, et al.)Courtesy of Volkow, Wang, & Begleiter, et al.)

296. Endogenous or Intrapersonal
Craving Triggers
• Boredom
• Fears
• Anxiety or depression
• Anger/resentments
• Guilt and Shame
• Others:
dishonesty, exhaustion, cocky,
complacent, self-pity, overconfidence,
impatience

297. Any Negative Mood State can
initiate a Craving Reaction
• HALT – Hungry, Angry,
Lonely, Tired
• RIID – Restless, Irritable,
Isolated, Discontent
• BAAD – Bored, Anxious,
Angry, Depressed

299. 3. Environmental or Interpersonal
Triggers and Cues via Dendritic
Emotional Memory “Spines, Bumps,
or Protrusions”

300. Environmental or Interpersonal
Triggers and Cues
• Any Sensory Input to addiction
memories: visual, odor, auditory, physical
withdraw, etc. – PTSD?
• Thoughts of using or of withdrawal
• Other Interpersonal factors:
relationship problems, social/vocational
pressures, no support system, negative life
events, untreated dual diagnoses

301. Craving can be causedCraving can be caused
by the sight, smell,by the sight, smell,
and taste ofand taste of
** a using partnera using partner
* a using place* a using place
* a dealer* a dealer
* cash* cash
* the drug itself* the drug itself

306. MEMORIES
Both Endogenous &
Environmental Triggers
activate memory pathways
where neurons search for the
most convenient way it resolved
the issues or needs in the past:
USE DRUGS!

307. Courtesy of Anna Rose Childress, Ph.D.

308. Memories
Formation & Role
In Drug Cravings

309. Neuro-development of
Memories
Dendritic “footprints, spines,
spikes, bumps, pimples,
appendages, protrusions”

310. Dendritic Memory Spines
• Amygdala process emotional memories,
hippocampus all other memories
• Also known as Bumps, Spikes – I like the term
memory protrusions = less triggering
• 4 to 6 sensory inputs of the same stimulus per
hour results in development of a semi-
permanent memory protrusion
• The more often a memory protrusion is
activated the larger it grows and the more
permanent it becomes

311. © Magal Mondin and Daniel Choquet, CNRS, Universite Bordeaux 2

313. Courtesy of Max Planck Institute of Neurobiology

314. Meso-Limbic Reward-Reinforcement
Circuitry of the MFB
 Phase I – Endogenous/Environmental Cue or memory
triggers the Ventral Tegmental Area to release dopamine
which activates core of Nucleus Accumbens Septi =
anticipation of use ON A MISSION! If initiated difficult to
stop
 Phase II – Cues or actual use of addictive drug activates
dopamine “go” switches of lateral hypothalamus and
Nucleus Accumbens (core and shell): COMPULSION FOR
MORE!
 Phase III – Control circuitry of the prefrontal cortex is
disrupted by excess dopamine and is inactivated: LOSS
OF CONTROL, CONTINUE DESPITE NEGATIVE
CONSEQUENCES

315. Stop Switch
Go
Switch
Brains Addiction Pathway

316. Prefrontal
Cortex
Nucleus
Accumbens
Arcuate
Nucleus Ventral
Tegmental
Area
Brain’s Addiction Pathway
Dopamine
Opioid Peptides
Glutamate
Courtesy of Dr. John Hart, Portland, Oregon

317. NIH Research Adds Hippocampal
Memory to the Craving Pathway
• Hippocampal memory process activates
• Lateral Septum via glutamate and this in turn
activates
• Ventral Tegmental Area (VTA) via gamma-
aminobutyric acid (GABA) that then activates
• Nucleus Accumbens Septi (“go switch”) via
dopamine
Luo, AH, et al. Science 7/15/11

318. Courtesy of Anna Rose Childress, Ph.D.

320. Craving and Relapse
Cue-Induced Brain Activity
Myrick et al. (2004). Neuropsychopharmacology, 29: 393.
• Brain regions activated while
viewing alcohol-related cues
Courtesy of Dr. John Hart, Portland, Oregon

321. Physiology of Craving
• Increased heart and pulse rate
• Specific electrical changes in skin
activity and spindle effects on EEG
• Increased peristalsis activity of gut
• Pupil dilatation and cortisone
stress reaction
• Two degree or more core
temperature drop
Childress AR, McLellan T, O’Brien CP Br. J. of Addict. 1986

322. Craving Extinction &
The Resilient Brain
Childress, AR, McLellan, T, O’Brien,
CP, (1986). British J. of Addictions,
81(5):655-660, May.

323. Key: Never Initiate any action to use
~ 95% of Slips = Relapse
Stop Signal Test (SST) Research
• Lawrence, AJ, Luty, J, Bogdan, NA, Sahakian, BJ,
Clark, L, (2009). Impulsivity and response inhibition
in alcohol dependence and problem gambling.
Psychopharm.(Berl.), 207(1):163-72, Nov.
• London, Edythe, Director Center for Addictive and
Biobehavorial Sciences, UCLA

325. Relapse Prevention
“tool kits”

331. Other Effective Relapse Prevention
Tools
• Emotional Freedom Techniques (EMDR, Brain
Spotting, Tapping, Elastic Snapping)
• Yoga Breaths, Somatics, Figure 8 Pacing
• Mindfulness meditation & other grounding
interventions, acupuncture, Laughter Yoga
• Consequence Reminders (family photo, car keys,
consequence cards)
• Paradoxical Interventions (emptied Librium capsules,
empty Copenhagen can, turn shirt inside out, wash
off and reapply makeup, et al.)

332. Gender Variance in Craving and
Relapse?
Women: brain areas associated with craving are
more activated by stress on fMRI scans.
Intrapersonal, Endogenous triggers
Men: drug cues/triggers activate craving areas of
the brain more = Environmental, Interpersonal
triggers Potenza, Marc et al. (2012) Am. J. of Psychiatry
But: David Sacks’ most common causes of relapse in
women: Romantic relationships too soon and
Unrecognized love, relationship or sex disorders
Sacks, David (2012), Psych Central

333. Limbic Area
• Role: Drive Generation (SURVIVAL)
• Intervention: Pharmacotherapy
Acute Reinforcing Effects
Courtesy of Dr. John Hart
Prefrontal Cortex
• Role: Executive Function
• Intervention: Counseling

334. Pharmacological Cue Extinction via
naltrexone and acamprosate

335. Hypersensitivity of Stress
Hormone Cycle in Addiction
1. Stress activates
hypothalamus
release of corti-
cotropin Releasing
factor (CRF)
2. CRF activates
pituitary release of
adrenocortico-
tropic hormone
(ACTH)
3.ACTH activates
kidney adrenal
glands to release
cortisol

336. “Addiction is a stress-induced defect in
midbrain’s ability to perceive pleasure”
Dr. Kevin McCauley
• CRF & ACTH are neurotransmitters as well as hormones they
modulate novelty-seeking and dopamine activity in the brain
• Severe stress increase risk-taking behaviors in all and
suppress dopamine’s ability to perceive reward, survival
reinforcement, “pleasure?” resulting in anhedonia since
• CRF & ACTH as neurotransmitters produce the unpleasant
emotional reactions associated with stress
• Cortisol usually turns off these secretions to terminate a stress
reaction but extreme stress overrules cortisol

337. Addictive drugs first release of dopamine in
the midbrain fools it as being a coping
mechanism for the relieve of stress
• Opiates & endorphins shown to also inhibit CRF & ACTH as
cortisol would naturally do
• But, withdrawal from opiates cause increase release of CRF, ACTH
and creates hypersensivity to stress that overrule cortisol’s
regulation of cycle = craving
• Cocaine directly releases the CRF and ACTH mistaken as part of or
covered by the rush, stimulant withdrawal also activates the
stress mechanism = craving
• Research: metyrapone validation (shuts off cortisol production
increasing CRF & ACTH) and CP-154,526 treatment (blocks CRF
and thus suppresses ACTH release) Heilig
and Koob 2007, Lowery et al. 2008

338. Also Neural Crux of Relapse with
Stress March 2013
VTA’s (ventral tegmental area): GABA-releasing
neurons, dopamine-releasing neurons and Kappa
opioid receptors interaction in stress. Drugs and
natural satiations release dopamine in the VTA. GABA
applies a brake to this via strengthening synapses
(known as long-term potentiation or LTP) but stress
interrupts this process leading to unabated dopamine
reinforcement. Nor-BNI blocks Kappa receptors in the
VTA and prevents stressed out rats from relapsing to
cocaine use
Graziane, Polter, Briand, Pierce, Kauer (2013), J. Neuron

339. Role of GABA & Glutamate
during Stress at VTA kappa (nor-BNI)
Inhibitory Excitatory

340. 4. Post Acute Withdrawal
Syndrome (PAWS) & Protracted
Withdrawal Syndrome:
Role in Evoking Slips and Relapses

341. Post Acute Withdrawal Syndrome
(PAWS) – episodic or recurrent
• Sleep Disturbances – insomnia, nightmares
• Memory Problems – Short-term, learning
• Thought Problems – concentration, rigidity, repetitive
thoughts/behaviors, abstract thinking & problem solving
difficulties
• Anxiety, irritability, hypersensitivity to stress
• Inappropriate emotional reactions, mood swings
• Physical and coordination difficulties, fatigue
• Syndrome persists for 3-6 months, sleep problems
maybe longer – can be up to 2 years

342. PAWS Cause is Unknown
Projected Etiology
• Slow reversing tolerance and tissue
dependence
• Returning neurotransmitter allostasis back
to homeostasis
• Developed hyperexcitability of neuronal
pathways
Ahveninen J, et al. (1999), Neurosci 268(2):57-60; Kiefer F, et al. (2002), Acta Psychiatr Scand
105(1):65-70; Bruijnzeel AW, et al. (2005), Brain Res Brain
Res Rev 49(3):505-28; Rimondini R, et al. (2008), Addict Biol 13(1):26-30

343. PAWS Treatment
• Clinical: CBT “grounding exercises”
• acamprosate for alcohol PAWS
• carbamazepine (Tegretol)
• Trazodone
• naltrexone

344. 5. Mental Health and/or other
Medical Conditions Must be
Stabilized and Medically
Managed During Recovery
May be Pre-Existing or
Addiction-Induced?

345. CO-OCCURING
DISORDERS:
Recognition and Treatment

346. Mental Health and/or other
Medical Conditions Must be
Stabilized and Medically
Managed During Recovery
May be Pre-Existing or
Addiction-Induced?

347. CO-OCCURING DISORDERS
Also Known As:
• Dual Diagnosis
• MICA (Mental Illness – Chemical Abuse)
• Co-Current Disorders
• Co-Morbidity or Co-Morbid Conditions
• Double Trouble

348. Definition
The existence in an individual of
at least one major mental health
disorder along with an alcohol or
drug use disorder
SAMHSA 2002; NIMH 1999

349. Incidence
• 44% of alcoholics and 64.4% substance
abusers admitted for treatment in 1990 had at
least one major mental illness
• Conversely 29-34% of all mentally ill patients
admitted for treatment in 1990 also had an
alcohol or drug use disorders.
Regier et al. 1990
• Note:Studies vary widely depending on the
populations studied

350. Co-Occurring Disorder, Dual
Diagnosis, MICA
• Prevalence depends on population studied
• 44% alcohol abusers and 64.4% other substance
abusers met diagnoses for at least one major
psychiatric disorder.
• 29% - 34% of those in mental health treatment
met diagnostic criteria for an addiction and related
disorder. Regier et al.,
1990; Merikangas, Stevens, & Fenton, 1996
• Recovery difficult if MH disorders are not
addressed

352. *
*
*DSM-5 replaces abuse and dependence with
Substance-Use Disorder Severity: Mild, Moderate, or Severe

353. Patterns of MICA
I.Preexisting Mental
Illness
II.Substance-Induced
Mental Illness
Need for Rule-Out Diagnosis, Provisional Diagnosis,
Working Diagnosis, Preliminary Diagnosis , or Decision
Making Diagnosis

354. DSM Five Axis Mental Health
Diagnosis & Assessment
(several hundred Disorders described & coded in DSM)
I. Clinical Disorder (egodystonic) & Focus
II. Personality Disorder (egosyntonic) or Mental
Retardation
III. General Medical Condition
IV. Psycho/Social & Environmental Factors
V. Global Assessment of Functioning Scale
Note: in DSM-5 2013 the 5 axis assessment was discontinued and replaced with
Severity Spectrums of Mild, Moderate or Severe for S-R and Addictive Disorders

355. • Obsessive Compulsive Disorder

356. Major Axis I Disorders
• Thought Disorders (Schizophrenia) 0.7-1.4% ap
• Affective Disorders (Depression) 8.6% ap, 15% lp
• Mood Disorders (Bipolar) 1.2% ap
• Anxiety Disorders & Phobias 16.4% lp
• Substance Use Disorders soon to be Addictions
and Related Disorders 9-12% ap, 30% lp
• Adjustment Disorders relatively high depending on cause
• Pervasive Developmental Disorders Mental Retardation .
78%, Developmental Disabilities 1.49%

362. Major Axis II Disorders
• Borderline Personality Disorder 2.0% ap
• Obsessive Compulsive PD 7.9% ap
• Paranoid PD 4.4% ap
• Antisocial PD 3.6% ap
• Schizoid PD 3.1% ap
• Schizotypal PD 3% ap
• Avoidant or Anxious PD 2.4% ap
• Narcissistic PD 0.5-1% ap
• Dependent PD 0.5% ap
• Histrionic PD 1.8% ap

363. CAVEAT!
ALL MENTAL HEALTH DISORDERS
SHOULD ONLY BE DIAGNOSED BY A
MENTAL HEALTH PROFESSIONAL
LICENSED TO MAKE SUCH DIAGNOSES!

364. Diathesis-Stress Model of
Neuropsychiatric Disorders
• HEREDITY
• ENVIRONMENTAL
Stressors & Poor Nutrition
• PSYCHOACTIVE DRUG TOXICITY /
NEUROTRANSMITTER ALLOSTASIS
Same combination of elements that
cause addictions

366. Enlarged Ventricles involved with loss of
Grey Matter in Schizophrenia

368. Anomalous Brain Activity in
Affective Disorders

369. Addiction – Mental Health
Interconnection = Neurotransmitters
Uppers Uppers & Psychedelics
All Addictive substances

370. Continued Conflicts with Treatment of
Co-Occurring Disorders

373. ● Need for “Rule-Out” careful diagnosis: Substance
Induced vs. Pre-Existing
Best Outcomes when both disorders treated at●
the same time in one treatment system
Same neurochemical imbalances involved with●
both disorders
Major MH disorders: Thought, Affective, Mood,●
Anxiety, and Personality

374. Four Quadrant Model: A Treatment
Guide? Kenneth Minkoff, M.D.
Quadrant 4
More Severe Mental
Disorder with
More Severe Substance
Use Disorder
Quadrant 3
Less Severe Mental
Disorder with
More Severe Substance
Use Disorder
Quadrant 1
Less Severe Mental
Disorder with
Less Severe Substance Use
Disorder
Quadrant 2
More Severe Mental
Disorder with
Less Severe Substance Use
Disorder

378. Note: Only 40% respond
positively to the first
medication used to treat
their mental health disorder

382. Key to Effective Mental Health
Treatment Outcomes
1. COMPLIANCE with medication dosage and
frequency as prescribed by their psychiatric
care provider
2. COMMUNICATION, active and continually
about medication and emotional feelings
with their mental health clinician or therapist

383. Dr. Kenneth Minkoff
Four Quadrant Treatment Model
Quadrant 4
More Severe Mental Disorder
More Severe Substance Use
Disorder
Quadrant 3
Less Severe Mental Disorder
More Severe Substance Use
Disorder
Quadrant 1
Less Severe Mental Disorder
Less Severe Substance Use
Disorder
Quadrant 2
More Severe Mental Disorder
Less Severe Substance Use
Disoder

384. Conclusion
Hope! Though the challenges
to maintaining sobriety are
daunting, developments in
treatment continue to improve
outcomes. Remember, the
qualities in those that makes
one vulnerable to addiction are
also qualities we look for in our
charismatic leaders.
Questions?

385. Recovery
• Continued Abstinence
• Discovery of Natural Highs
• Recovery of neurotransmitters and
of natural brain functions
• Positive lifestyles and quality of
life enhancements
• Remember: Not an Event but a Process
One does not cure addiction, you treat it and manage it like any
other chronic persistent medical disorder

386. Seminar on Neuroscience of Addiction and
Recovery is Completed
Great Work All and Thank You All for Attending

387. Questions?
Audience at completion of my presentations

388. Thank You!
Darryl Inaba, PharmD.,
CATC-V, CADC III
Eighth Edition