Nora D' Volkow, M'D'

1
Research on
METHAMPHETAMINE
Where Do We Need To Go?
Nora D. Volkow, M.D. Director National Institute
on Drug Abuse
2
In 2003, over 12.3 million people age 12 or older
reported having used methamphetamine at least
once in their lifetime BUT Is methamphetamine
abuse increasing?
Source 2003 NSDUH, SAMHSA
3
According to the Monitoring the Future Study
Methamphetamine is not Increasing

P lt .05
Percent of Students Reporting Use of
Methamphetamine in Past Year, by Grade
4
Methamphetamine Treatment Admissions Have Been
Increasing
60 50 40 30 20 10 0
52
42
36
32
32
32
30
Per 100,000 Aged 12 or Older
25
22
14
10
1992 1993 1994 1995 1996 1997 1998 1999
2000 2001 2002
Methamphetamine/Amphetamine Treatment Admission
Rate 1992 -2002
2002 SAMHSA Treatment Episode Data Set
5
Concerns with Methamphetamine

• Neurotoxic in animal models of
• drug self administration
• Highly addictive
• Intoxication associated with
• behaviors that increase risks for
• infection with HIV and HCV
• Can be easily manufactured by
• small clandestine laboratories

6
Dopamine Neurotransmission
frontal cortex
nucleus accumbens
VTA/SN
7
Brain Dopamine System
DA Transporters
DA Receptors
DA
DA
Anatomy
DA
DA
DA
DA
DA
signal
Dopamine Cell
Metabolism
8
Dopamine Transporters in Methamphetamine Abusers
(Bmax/Kd)
Normal
Meth
Controls
Abusers
p lt 0.0002
Methamphetamine abusers have significant
reductions in dopamine transporters
BNL UCLA SUNY
9
The Abnormalities are Similar Though Less Severe
Than Those in Parkinsons Disease
Could METH abuse increase the risk of Parkinsons
disease as people grow older?
10
Dopamine Transporters in Methamphetamine Abusers
Motor Task
Loss is associated with slowing of motor
reactions.
(Bmax/Kd)
Dopamine Transporter
Time Gait
Memory Task
(seconds)
Loss is associated with memory impairment.
Dopamine Transporter
Bmax/Kd
BNL/UCLA/SUNY
Delayed Recall
(words remembered)
NIDA, DOE (OBER), ONDCP
11
Partial Recovery of Brain Dopamine Transporters
in Methamphetamine (METH) Abuser After Protracted
Abstinence
METH Abuser (1 month detox)
Normal Control
METH Abuser (24 months detox)
Source Volkow, ND et al., Journal of
Neuroscience 21, 9414-9418, 2001.
12
Brain Dopamine System
DA Transporters
DA Receptors
DA
DA
Anatomy
DA
DA
DA
DA
DA
signal
Dopamine Cell
Metabolism
13
Decreased Metabolism in Methamphetamine Abusers
Region/Gray Matter)
P lt 0.001
14
METH abusers lt controls
Early Detoxification
Late Detoxification
(FWHM 16mm, pixel threshold 0.001)
15
How Can Science Help us Guide Prevention and
Treatment Efforts?
Research Has Shown that Adolescents Report
Physical Appearance and Performance Abilities
To Be Strong Motivators for Such Health-Related
Behaviors As Quitting Smoking
Source Riedel, BW, Drug and Alcohol Dependence,
68, 167-174, 2002.
16
METH Use Leads to Severe Tooth Decay
Source Richards, JR and Brofeldt, BT, J
Periodontology, August 2000.
METH Mouth
Source The New York Times, June 11, 2005.
17
As we grow older we lose dopamine transporters in
our brain methamphetamine accelerates this loss
28 years
Will affect motor reflexes
44 years
Methamphetamine 28 years
Will affect memory
84 years
18
(No Transcript)
19
Methamphetamine in the HIV Epidemic

• METH has been shown to alter immune function
• Risky sexual behavior that occurs during METH
• intoxication increases the risk of HIV
  infection
• Physiological changes resulting from METH
• use may increase infectivity (e.g., erosion of
• normal protective epithelial layer)

20
Emergency Department (ED)Visits
Involving Amphetamines/Methamphetamine Increased
54 Between 1995 and 2002 in the U.S.
Source OAS, SAMHSA, Drug Abuse Warning Network
(DAWN), 2002 (03/2003 update).
21
Aggressive Action Is Needed To Stop METH Use
Its Serious Consequences
We Need to Work TOGETHER To Make the Public
Aware of the Drugs Toxic and Addictive
Properties And to Develop Treatments that will
counteract neuroadaptations that underlie the
addictive process and reverse METHs neurotoxic
effects
22
2002 Data on Drug Treatment Admissions Indicate
that in 16 US States METH Was the Primary Drug
Problem at the Time of AdmissionAND In 14 of
These States There Were More Admissions Resulting
From METH than from Heroin and Cocaine Combined
Source 2002 SAMHSA Treatment Episode Data Set
23
Brain Glucose Metabolism in METH Abusers
Whole Brain
Metabolic Rate
(micromol/100 gr/min)
Controls
METH
p lt 0.05
BNL, UCLA, SUNY
24
Brain Metabolism in METH Abusers with Abstinence
Thalamus
Striatum
Control
Ratio
METH Abuser (3 m Detox)
129, p lt 0.015 2.76.7, p 0.34
METH Abuser (13 m Detox)
25
METH abusers gt controls
5.0
Early Detoxification
4.0
3.0
Late Detoxification
(FWHM 16mm, pixel threshold 0.001)