addictions and the brain
DESCRIPTION
Dr. Daniel Boone, Medical Director of La Hacienda Treatment Center, discusses the correlation between addictions and our brains.TRANSCRIPT
Addictions and the Brain
Acknowledgements
• La Hacienda Treatment Center
• American Society of Addiction Medicine
• National Institute of Drug Abuse
Definition
• A primary, progressive biochemical, psychosocial, genetically transmitted chronic disease of relapse who’s hallmarks are denial, loss of control and unmanageability.
DSM IV Criteria for dependency: At least 3 of the 7 below
1. Withdrawal2. Tolerance3. The substance is taken in larger amounts or over a longer period
than was intended.4. There is a persistent desire or unsuccessful efforts to cut down or
control substance use.5. A great deal of time is spent in activities necessary to obtain the
substance, use the substance, or recover from its effects.6. Important social, occupational, or recreational activities are given
up or reduced because of the substance use.7. The substance use is continued despite knowledge of having a
persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.
Dispute between behavior and disease
Present understanding of the Hypothalamus location of the
disease hypothesis.
Dispute regarding behavior versus disease
00
5050
100100
150150
200200
00 6060 120120 180180
Time (min)Time (min)
% o
f B
asal
DA
Ou
tpu
t%
of
Bas
al D
A O
utp
ut
NAc shellNAc shell
EmptyEmpty
BoxBox FeedingFeeding
Source: Di Chiara et al.Source: Di Chiara et al.
FOODFOOD
100100
150150
200200
DA
Co
nce
ntr
ati
on
(%
Bas
elin
e)D
A C
on
cen
tra
tio
n (
% B
asel
ine)
MountsMountsIntromissionsIntromissionsEjaculationsEjaculations
1515
00
55
1010
Co
pu
latio
n F
req
ue
nc
yC
op
ula
tion
Fre
qu
en
cy
SampleNumberSampleNumber
11 22 33 44 55 66 77 88 99 1010 1111 1212 1313 1414 1515 1616 1717
ScrScrScrScrBasBasFemale 1 PresentFemale 1 Present
ScrScrFemale 2 PresentFemale 2 Present
ScrScr
Source: Fiorino and PhillipsSource: Fiorino and Phillips
SEXSEX
Natural Rewards Elevate Dopamine Natural Rewards Elevate Dopamine LevelsLevels
Natural Rewards Elevate Dopamine Natural Rewards Elevate Dopamine LevelsLevels
00100100200200300300400400500500600600700700800800900900
1000100011001100
00 11 22 33 44 5 hr5 hr
Time After AmphetamineTime After Amphetamine
% o
f B
as
al
Re
lea
se
% o
f B
as
al
Re
lea
se
DADADOPACDOPACHVAHVA
AccumbensAccumbens AMPHETAMINEAMPHETAMINE
00
100100
200200
300300
400400
00 11 22 33 44 5 hr5 hrTime After CocaineTime After Cocaine
% o
f B
as
al
Re
lea
se
% o
f B
as
al
Re
lea
se
DADADOPACDOPACHVAHVA
AccumbensAccumbensCOCAINECOCAINE
00
100100
150150
200200
250250
00 11 22 33 44 5hr5hrTime After MorphineTime After Morphine
% o
f B
as
al
Re
lea
se
% o
f B
as
al
Re
lea
se
AccumbensAccumbens
0.50.51.01.02.52.51010
Dose (mg/kg)Dose (mg/kg)
MORPHINEMORPHINE
00
100100
150150
200200
250250
00 11 22 3 hr3 hrTime After NicotineTime After Nicotine
% o
f B
as
al
Re
lea
se
% o
f B
as
al
Re
lea
se
AccumbensAccumbensCaudateCaudate
NICOTINENICOTINE
Source: Di Chiara and ImperatoSource: Di Chiara and Imperato
Effects of Drugs on Dopamine LevelsEffects of Drugs on Dopamine LevelsEffects of Drugs on Dopamine LevelsEffects of Drugs on Dopamine Levels
Post-Chronic Amphetamine (10 days)
Pre-Amphetamine/Control
Striatal FDOPA Activity
4 weeks
6 months
1 year
2 years
Superior Inferior
Dopamine Transporters in Methamphetamine AbusersDopamine Transporters in Methamphetamine Abusers
Methamphetamine abusers have significant reductions in dopamine Methamphetamine abusers have significant reductions in dopamine transporters.transporters.
Normal ControlNormal Control
Methamphetamine AbuserMethamphetamine Abuser p < 0.0002p < 0.0002
Do
pam
ine
Tra
nsp
ort
ers
(Bm
ax/
Kd
)
NormalControls
MethAbusers
1.0
1.2
1.4
1.6
1.8
2.0
2.2
2.4
BNL - UCLA - SUNYBNL - UCLA - SUNYNIDA - ONDCP - DOENIDA - ONDCP - DOE
Dopamine Transporters in Methamphetamine AbusersDopamine Transporters in Methamphetamine Abusers
BNL/UCLA/SUNYBNL/UCLA/SUNY
NIDA, ONDCP, DOENIDA, ONDCP, DOE
Motor TaskMotor TaskLoss of dopamine transporters Loss of dopamine transporters in the meth abusers may result in the meth abusers may result in slowing of motor reactions.in slowing of motor reactions.
Memory TaskMemory TaskLoss of dopamine transporters Loss of dopamine transporters in the meth abusers may result in the meth abusers may result in memory impairment.in memory impairment.
7 8 9 10 11 12 131.0
1.2
1.4
1.6
1.8
2.0
Time Gait(seconds)
468101214161.01.2
1.4
1.6
1.8
2.0
Delayed Recall(words remembered)
Do
pam
ine
Tra
nsp
ort
erB
max
/Kd
CocaineCocaine
FoodFood
DA
D2
Rec
epto
r A
vai l
abil
ity
MethMeth
AlcoholAlcohol
Dopamine D2 Receptors in Addiction
Experimentalgroups
Controlgroups
Drug Use Addiction TreatmentNormal
Challenge:
Three Major Relapse Pathways
I. Cross Addicting DrugsII. People/Place/ThingsIII. B.H.A.L.T.
Cross Addicting Drugs
a. Chemical of choice
b. Related drugs
c. Tobacco
d. Life long relapse pathway
People/Place/Things
a. History of discovery
b. Three month limit for relapse
B.H.A.L.T.
a. Boredom
b. Hunger
c. Anger/emotions
d. Loneliness
e. Tiredness
Relapse Prevention Medications
I. Antabuse
II. Campral
III. ReVia
IV. Vivitrol
V. Off label
Antabuse
a. Mechanism of action
b. Dosing
c. Side Effects
d. Efficacy
Campral
a. Mechanism of action
b. Dosing
c. Side Effects
d. Efficacy
ReVia
a. Mechanism of action
b. Dosing
c. Side Effects
d. Efficacy
Vivitrol
a. Mechanism of action
b. Dosing
c. Side Effects
d. Efficacy
Off label
Phase 3 Clinical TrialsOn A Number of Promising Drugs
Phase 3 Clinical TrialsOn A Number of Promising Drugs
Cabergoline
Disulfiram (Antabuse)
Reserpine
Selegiline
Cabergoline
Disulfiram (Antabuse)
Reserpine
Selegiline
CocaineCocaine MethamphetamineMethamphetamine
BupropionBupropion LofexidineLofexidine
OpiatesOpiates
Cocaine Medication Development ProjectsCocaine Medication Development Projects
Phase II ScreenPhase II Screen Phase IIIPhase III
DisulfiramSelegiline TSDisulfiramSelegiline TS
Phase IPhase I Phase IIPhase II
ButorphanolDAS 431GBR 12909MetyraponeModafinilNS 2359Tolcapone
ButorphanolDAS 431GBR 12909MetyraponeModafinilNS 2359Tolcapone
BP 4897Cocaine VaccineDextromethorphanIsradipineLamotrigineMemantineOndansetronSibutramine
BP 4897Cocaine VaccineDextromethorphanIsradipineLamotrigineMemantineOndansetronSibutramine
AmantadineAmlodipineBaclofenBupropionButorphanolCabergolineCaptoprilClopidogrelDisulfiramGabapentinMemantineMethylphenidateNaltrexoneOxazepamPemolinePropranololReserpineRisperidoneSertralineTaurineTiagabineVenlafaxine
AmantadineAmlodipineBaclofenBupropionButorphanolCabergolineCaptoprilClopidogrelDisulfiramGabapentinMemantineMethylphenidateNaltrexoneOxazepamPemolinePropranololReserpineRisperidoneSertralineTaurineTiagabineVenlafaxine
Opiate Medication Development ProjectsOpiate Medication Development Projects
Phase IPhase I
CycloserineCycloserineDepot NaltrexoneDepot NaltrexoneEnadolineEnadolineLamotrigineLamotrigineTramadolTramadol
Phase IIPhase II Phase IIIPhase III
BuprenorphineBuprenorphine
Buprenorphine/NaloxoneLofexidineBuprenorphine/NaloxoneLofexidine
BupropionBuspironeClonidineLofexidineMemantineMethylphenidateMidazolam/N20NaloxoneNaltrexoneNefazedone
BupropionBuspironeClonidineLofexidineMemantineMethylphenidateMidazolam/N20NaloxoneNaltrexoneNefazedone
Methamphetamine Addiction Pharmacotherapiesin Clinical Trials
Methamphetamine Addiction Pharmacotherapiesin Clinical Trials
AmlodipineBaclofenDesipramineFluoxetineFlupenthixolGabapentinIsradipineOlanzapineOndansetronPemolineSelegilineVenlafaxine
AmlodipineBaclofenDesipramineFluoxetineFlupenthixolGabapentinIsradipineOlanzapineOndansetronPemolineSelegilineVenlafaxine
Phase IPhase I Phase IIPhase II
BupropionDisulfiramLobelineReserpineSelegiline
BupropionDisulfiramLobelineReserpineSelegiline
Dual Diagnosis
1. Prevalence
2. Testing
3. Treatment
Spiritual Component of Recovery
