Color

Yale H. Caplan, Ph.D.,
DABFT
University of Maryland,
School of Pharmacy,
Baltimore, MD
1
 
 
 
Differentiate the licit and illicit use of
stimulants in the workplace
Describe the impact of drugs (stimulants)
on the performance of safety sensitive
tasks
Describe the process of federally
regulated testing for drug (stimulant)
abuse
2
The Nature of Stimulant Abuse
 
 
Stimulant medications such as methamphetamine
(Desoxyn®), amphetamine (Adderall®), and
methylphenidate (Ritalin®) are classified by the DEA as
Schedule II controlled medications
•  High potential for abuse
•  Severe psychological or physical dependence
•  Highly reinforcing due to their activation of the nucleus
accumbens (“pleasure center”)
The nature of substance abuse is such that the user is
secretive and deceptive about his/her illicit use
3
Effects of Prescription Stimulants
 
 
 
Effects can include nervousness and insomnia, loss of appetite,
nausea and vomiting, dizziness, palpitations, headaches, changes
in heart rate and blood pressure (usually elevation of both, but
occasionally depression), skin rashes and itching, abdominal
pain, weight loss, and digestive problems, toxic psychosis, and
psychotic episodes. Long-term effects or high doses can result in
compulsive use, feelings of hostility, paranoia, hallucinations,
excessive repetition of movements, and formicaton (sensation of
bugs and worms crawling under the skin)
Taking high doses of a stimulant may result in dangerously high
body temperatures and an irregular heartbeat
Additionally, there is also the potential for cardiovascular failure
(heart attack) or lethal seizures.
4
Prescribed Stimulants
 
 
Stimulants such as Ritalin and Concerta (methylphenidate)
and Adderall and Dexedrine (amphetamine) are prescribed
to treat certain conditions, principally attention deficit
hyperactivity disorder (ADHD)
•  Although the drugs are stimulants, in those who have a
hyperactivity disorder they have the reverse effect and
produce a calming and focusing effect
People without ADHD who abuse these drugs do so
seeking the stimulant effect
•  The drugs increase blood pressure and heart rate and
produce speed-like effects such as loss of appetite,
increased concentration, wakefulness, and in some
cases euphoria
5
Abuse of Prescribed Stimulants
 
 
Stimulants such as Ritalin and Concerta (methylphenidate)
and Adderall and Dexedrine (amphetamine) are abused at
a higher rate among college students
•  They are used to stay awake and alert beyond their
natural ability, in order to continue studying or partying
Stimulants are sometimes abused for “performance
enhancement” (e.g., weight loss, better focus, increased
attention), as well as to get high, as in drivers
•  Abusers of these drugs crush the tablets and snort,
inject, or take them orally
6
Other Prescribed Stimulants
 
 
 
 
 
Modafinil (Provigil/Alertec/Modavigil) is an analeptic drug
approved by the (FDA) for the treatment of narcolepsy,
shift work sleep disorder, and excessive daytime
sleepiness associated with obstructive sleep apnea.
Adrafinil is a prodrug; it is primarily metabolized in vivo to
Modafinil
Armodafinil is a new version of Modafinil
Norepinephrine reuptake inhibitors (NRIs)
•  Strattera (atomoxetine)
•  Edronax (reboxetine)
Norepinephrine-dopamine reuptake inhibitors (NDRIs)
•  Wellbutrin, Zyban (bupropion)
7
Other Common Stimulants
 
 
 
 
 
Caffeine
Nicotine
Ephedrine
Pseudoephedrine
Inhalers
•  L-metamfetamine
•  L-desoxyephedreine
•  L-methamphetamine
8
“Crystal Meth”
Illicit Stimulants
 
 
 
Cocaine
Methamphetamine
Designer drugs
•  Ecstasy-type
• MDMA
• MDA
• MDEA
 
•  Phenethylamines
•  Tryptamines
Newer drugs
9
Examples of Prescription Stimulant Abuse—
A College Student
(http://www.kansan.com/news/2006/feb/02/drugs/)
Sarah’s mouth is dry. She’s constantly thirsty. The Concerta she
took did its job. She finished her paper hours ago. Now, she just
has to keep busy. She cleans her room and organizes the books on
her shelf by color and by size. She lies in bed writing letters she will
never send to friends she hasn’t talked to in years. She has a lot to
say, but no one is awake to listen. Things will be like this —
methodical, obsessive — until the stimulant wears off.
The thing is, Sarah doesn’t have ADHD. She doesn’t have a
prescription. But her freshman-year roommate did. Sarah’s first
experience with stimulants was in eighth grade, when a friend with
ADHD who didn’t like to take all her medication gave Sarah Adderall
to get rid of the extra pills in her bottle. After that, Sarah continued
to take Adderall occasionally throughout high school.
Sarah says that when she takes Concerta she often won’t sleep for
48 hours or eat for a day and a half.
10
Purpose for Drug Testing
 
 
 
 
 
Drug abuse affects not only the user but those
around them as well
Workplace safety—A drug-impaired worker may
be a hazard to themselves, others, and to
property
Sports—Discourage competitors from gaining an
artificially derived advantage over an opponent.
Health settings—Diagnosis of drug use,
compliance monitoring
Legal settings—Evidentiary
11
Drug Testing in the Workplace
 
In a drug-free workplace, the employer has
taken steps and initiated policies to ensure that
employees and vendors are not:
•  Taking or using alcohol or drugs
•  Selling drugs
•  Affected by indulging in alcohol or drugs outside of the
workplace during non-work time
 
 
 
Additionally, the goal is to encourage an
employee with a substance abuse problem to
seek treatment, recover, and return to work
Deterence based program
Urine is specimen of choice for testing
12
Urine
13
History of Urine Drug Testing
 
1983
•  NTSB recommendations to DOT resulting from
Alcohol and Drug related accidents, 7 in
railroads
•  FRA with NIDA began to consider regulations
 
1983-1986
•  Voluntary programs implemented oil/
chemical, transportation and nuclear
industries
14
History of Urine Drug Testing
 
1986
•  Commission on Organized Crime says drug
abuse by Federal, State and Local
Governments unacceptable
 
March, 1986
•  NIDA landmark conference
 
September 15, 1986
•  President Regan Executive Order 12565
for federal agencies
15
History of Urine Drug Testing
 
 
 
July 7, 1987
•  Public law 100-71 Seet503
authorized testing
April 11, 1988
•  HHS Mandatory Guidelines National
Laboratory Certification Program
June 6, 1989
•  Nuclear Regulatory Commission
(implemented by Nov. 3, 1990)
16
History of Urine Drug Testing
 
 
 
DOT interim final rule Nov. 21, 1986
•  6 DOT Modes authorized
December 1, 1989 Final rule
•  Implementation by Jan 2, 1990
Impetus was subway accident in New York
City where engineer was under the
influence of alcohol
17
History of Urine Drug Testing
 
 
Omnibus Transportation Employee
Testing Act of 1991 expanded testing
broadly
Final DOT Rules 1994
•  Effective Jan. 1, 1995 for large
companies
•  Effective Jan. 1, 1996 for small
companies
•  Alcohol testing added
18
Urine – General Characteristics
 
 
 
 
 
 
Static, not dynamic
Water-like liquid
Volume per day produced is variable
Random specimen collected
Concentration is a function of water
intake
How we characterize it chemically:
•  pH
•  Creatinine
•  Specific gravity
19
Federally Regulated Drug Testing
 
 
 
Urine only
HHS – Federal Employees
Half-million
HHS mandatory guidelines
DOT – Regulated Industries
Twelve million
Use HHS laboratories
20
Urine Collection
 
Generally not observed
•  Subject to adulteration by specimen
donor
 
Observed
•  Military
•  Others
21
Collection of Specimens
Collection Site
Lab Accessioning
Courier
X
X
X
X
Accession
":
23-31560
4-1
CUSTODY AND
CONTROL
FORM
X
X
X
X
CUSTODY AND
CONTROL
FORM
Accession
":
23-31560
4-1
  Right to Privacy
  Chain of Custody (CCF)
•  Integrity, Security, and
Identification
  Temperature Recording
  Tamper-Evident Bottle Seal
22
Accessioning
Accession
":
23-3156
04-1
 
 
 
 
Limited Access
•  Secure Area
Chain of Custody
•  Aliquoting
•  Intra-laboratory CCF
Discrepancies/Cancellation
Temporary Storage
CUSTODY
AND
CONTROL
FORM
Discrepancy
Canceled or test not performed
LIMS
CUSTODY
AND
CONTROL
FORM
CUSTODY
AND
CONTROL
FORM
LCS
Review
Report
to MRO
23
Analytical Techniques:
Testing for Abused Drugs
 
 
Screen
•  Series of initial tests designed to
distinguish negatives from
presumptive positive samples
Confirm
•  Second test used to positively
identify a drug or drug metabolite
24
Initial Testing
Accessioning
 
CUSTODY
AND
Accession
":
23-3156
04-1
CUSTODY
CONTROL
FORM
AND
CONTRO
L FORM
Adulteration Testing
Initial Test - Immunoassay
Negative
Positive
LIMS
 
CUSTODY
AND
CONTROL
FORM
CUSTODY
AND
CONTROL
FORM
LCS
Review
Report
to MRO
Immunoassay
•  enzyme (EIA)
•  radioactive
(RIA)
•  fluorescence
(FPIA)
•  kinetic
mobility
(KIMS)
Quality Control
•  calibrators
•  controls
•  linearity
25
Principle of Immunoassays
Antibody
+
=
Drug Molecules
Antibody
Bound Drug
26
Confirmation Testing
Accessioning
Storage of
AND
CONTROL
Accession
":
23-3156
04-1
 
 
Freezer
Positives
CUSTODY
FORM
Quality Control
•  Calibrators
•  Controls
•  Linearity
Positive Specimen
Criteria
CUSTODY
AND
Accession
":
23-3156
04-1
CONTROL
FORM
CUSTODY
AND
CONTROL
FORM
ConfirmationTest - GC/MS
Positive
Negative
LIMS
CUSTODY
AND
CONTROL
FORM
CUSTODY
AND
CONTROL
FORM
LCS
Review
Report
to MRO
27
28
29
Review of Results
Initial Test - Immunoassay
Negative
Confirmation Test - GC/MS
Positive
Positive
Negative
LIMS
CUSTODY
AND
CONTROL
FORM
CUSTODY
AND
CONTROL
FORM
 
 
 
LCS
Review
Report
to MRO
Technicians, Supervisors
Laboratory Certifying Scientists
(LCSs)
Medical Review Officers (MROs)
•  Verifies all laboratory results
30
Forensic Urine Drug Testing
Accessioning
Collection Site
Courier
Accession
":
23-3156
04-1
Freezer
Storage of
Positives
CUSTODY
CUSTODY
AND
CONTROL
FORM
Accession
":
23-3156
04-1
CUSTODY
AND
AND
CONTROL
CONTROL
Accession
":
23-3156
04-1
FORM
FORM
CUSTODY
AND
Adulteration Testing
CUSTODY
CONTRO
L FORM
AND
Discrepancy
Initial Test - Immunoassay
Canceled or test
CONTRO
L FORM
Confirmation Test - GC/MS
not performed
Negative
Positive
Positive
Negative
LIMS
CUSTODY
AND
CONTROL
FORM
CUSTODY
AND
CONTROL
FORM
LCS
Review
Report
to MRO
31
Urine Drug Testing
Advantages
 Extensive
Base
 Accurate
 Mature
Scientific
& Reliable
Technology
Disadvantages
 2-3
Day Window of
Detection
 Easy
to Adulterate
 No
Dose/
Concentration
relationship
32
What drugs do laboratories test for?
(a) 
(b) 
(c) 
(d) 
(e) 
Marijuana metabolites
Cocaine metabolites
Amphetamines
Opiate metabolites
Phencyclidine (PCP)
Must not test for other drugs
33
What are the cutoff concentrations for
initial and confirmation tests?
(Original)
Drug
 
 
 
 
 
 
 
 
Screen
Confirm
Marijuana metabolites …………50
THCA………………………………………………… 15
Cocaine metabolites ………… 300
Benzoylecgonine……………………………… 150
Phencyclidine ……………………… 25 …………… 25
Amphetamines …………………1000
Amphetamine ……………………………………… 500
Methamphetamine*……………………………… 500
34
Methamphetamine Reporting Rule
 
 
As condition for lab to report specimen
Positive Methamphetamine
Laboratory must identify:
•  Methamphetamine > 500 ng/mL
& Amphetamine > 200 ng/mL
 
(Amphetamine results between 200 and
499 ng/mL do not appear on laboratory
report to MRO)
35
Opiate Cutoff Concentrations
Effective December 1, 1998
 
 
Drug
Screen
Opiates & Metabolites 2,000
Morphine
Codeine
*6-acetylmorphine
Confirm
2,000*
2,000
10
*Test for 6-AM when the morphine
concentration exceeds 2,000 ng/mL
Effective October 1, 2010
 
6-Acetylmorphine tested independently
36
DHHS Guidelines (11/25/2008)
(effective 10/1/10 to include MDMA, MDA, MDEA)
Initial Test Analyte
Amphetamines
AMP/MAMP
MDMA
Initial Test
Cutoff (ng/
mL)
500
500
Confirmation Test
Analyte
Confirmation
Cutoff (ng/mL)
Amphetamine
Methamphetamine
250
250
MDMA
MDA
MDEA
250
250
250
37
Specimen Validity Testing (SVT)
Requirements for Federal Employee
Drug Tests
 
 
 
Creatinine and specific gravity
•  Determine the creatinine on every specimen
•  Determine the SG if creatinine <20 mg/dL
•  SG to 4 decimal places if reporting a
specimen as substituted or as invalid based
on creatinine and SG
Determine the pH on every specimen
Perform one or more validity tests for
oxidizing adulterants on every specimen
38
Mandatory Guidelines Effective
November 1, 2004:
 
 
Substituted
Creatinine < 2 mg/dL & SG ≤1.0010
Creatinine < 2 mg/dL & SG >1.0200
SG measured to 4 decimal places
Dilute
Creatinine
2 – 20 mg/dL
SG
1.0010 – 1.0030
39
Mandatory Guidelines Effective
November 1, 2004:
 
 
 
 
 
A urine specimen is reported adulterated when:
pH < 3
pH > or = 11
Nitrite concentration > or = 500 mcg/mL
•  two different tests required; see Sec 2.4
Chromium (VI) concentration > or = 50 mcg/mL
•  two different tests required; see Sec 2.4
40
Forensic Drug Testing
Other areas
 
 
 
 
Non-regulated workplace
•  Additional drugs
U.S. Military
Courts
Parole and probation
41
Medical Review Officer
 
Reviews laboratory results for evidence of
legitimate medical use
42
43
44
Positive Prevalence Rate for MDMA
(Urine Testing)
2004
2005
2006
2007
2008
2009
N
(Thousands)
68
114
165
256
240
217
% Positive
0.042%
0.031%
0.028%
0.020%
0.015%
0.015%
45
Estimated Number (in thousands) of New Ecstasy
Users per Year (ages 12 or older) and Estimated
Number of Ecstasy-Related ED Visits, 1992 to 2009
46
MRO Review of Amphetamines
HHS DWP SAMHSA Study, 2009
Regulated
Non-Regulated
%MRO
Verified
24
20
%MRO
Reversed
76
80
47
What is the Evidence for Cognitive
Enhancement/Impairment from Stimulants?
 
 
 
 
Ritalin enhances cognitive performance including working
memory and executive functions in adults and children diagnosed
with ADHD (Kempton et al., 1999)
Recent investigations on amphetamine/methamphetamine have
documented deficits in learning, delayed recall, processing speed,
and working memory (Lundqvist, 2005)
MDMA users exhibit difficulties in coding information into longterm memory, display impaired verbal learning, are more easily
distracted, and are less efficient at focusing attention on complex
tasks (Lundqvist, 2005)
Chronic cocaine users display impaired attention, learning,
memory, reaction time and cognitive flexibility (Lundqvist, 2005)
48
Amphetamine: Performance Impairment
49
Cognitive Deficits Associated With Chronic
Stimulant Abuse
 
 
“Cognitive Sequelae of Intravenous Amphetamine SelfAdministration in Rats: Evidence for Selective Effects on
Attentional Performance” Dalley, et al.,
Neuropsychopharmacol (2005) 30: 525-37
Study examined short and long-term cognitive
consequences of intravenously self-administered
amphetamine
•  Short Term Effects: The results revealed a selective and reproducible
pattern of deficits on the serial reaction time task following
withdrawal from amphetamine, with deleterious effects on the speed
and accuracy of responding as well as increased omission errors
•  Long Term Effects: Following a 2-month abstinence period,
abnormalities in the subsequent effects of acute noncontingent
amphetamine were found, with increased omissions, slower response
times, and reduced impulsivity
50
MDMA, MDA, MDE
 
 
 
 
 
Easily synthesized in clandestine laboratories
More than 20 pathways are known for synthesis
of MDMA and MDE
Usually marketed as pills with a variety of logos
alluding to the “rave” way of life
Dosages vary: one survey indicated 64-175 mg
of MDEA present
Can be detected in urine, oral fluid, hair and
sweat
51
MDMA
 
 
 
 
 
 
Street names: MDMA, Ecstasy, E, X, XTC,
Adam, M&M
Chemical name: 3,4-Methylenedioxymethamphetamine
Schedule: I
Pharmacology: cardiovascular and
neurologic sympathomimetic effects
Signs: Mydriasis
Recreational Dosage: 100-150 mg oral
52
MDMA in Plasma and Oral Fluid
53
MDMA
 
 
 
 
 
 
Half-life: 7.6 hrs
Metabolites: MDA
Urine excretion: 65% MDMA; 7% MDA
Detection time: 1-3 days
Screen: Methamphetamine,
amphetamine
•  Immunalysis Methamphetamine EIA
MDMA = 135% CR; MDA = 0% CR
Confirmation: MDMA & MDA
54
MDA
 
 
 
 
 
 
Street names: MDA, love drug, love pill
Chemical name: 3,4-Methylenedioxyamphetamine
Schedule: I
Pharmacology: cardiovascular and neurologic
sympathomimetic effects
Signs: Mydriasis
Recreational Dosage: 100-150 mg oral
55
MDA
 
 
 
 
 
 
Half-life: 25 hrs
Metabolites: MDA
Urine excretion: MDA
Detection time: 1-3 days
Screen: Amphetamine
•  Online Amphetamines
MDA = 32% CR; MDMA = 0% CR
Confirmation: MDA
56
MDE
 
 
 
 
 
 
Street names: MDEA, MDE, Eve, intellect
Chemical name: 3,4-Methylenedioxyethylamphetamine
Schedule: I
Pharmacology: cardiovascular and neurologic
sympathomimetic effects
Signs: Mydriasis
Recreational Dosage: 100-150 mg oral
57
MDE
 
 
 
 
 
 
Half-life: 7.5 hrs
Metabolites: MDA
Urine excretion: 19% MDEA; 28% MDA
Detection time: 1-3 days
Screen: Methamphetamine, amphetamine
•  Online Amphetamines
MDA = 32% CR
•  Immunalysis Methamphetamine EIA
MDE = 10% CR; MDA = 0% CR
Confirmation: MDEA, MDA
58
Ecstasy-Type Drugs: Summary
 
 
 
MDMA
•  Methamphetamine screen
•  Confirm: MDMA, MDA
MDA
•  Amphetamine screen
•  Confirm: MDA
MDEA
•  Amphetamine screen
•  Confirm: MDEA, MDA
59
New Psychoactive Drugs
Last year, 24 new
"psychoactive substances"
were identified in Europe,
almost double the number
reported in 2008, according to
the Lisbon-based European
Monitoring Centre for Drugs
and Drug Addiction, or
EMCDDA.
60
 
 
 
 
 
Synthetic stimulant and entactogen
“4-MCC”, “meph”, “drone”, “MCAT”
Synthesized in 1929 but did not become widely
known until it was rediscovered in 2003
In the UK, A survey of 1000 secondary school
pupils and university students in Tayside,
conducted in February 2010, found that 20% of
them had previously taken mephedrone.
Banned in mid 2010 in UK, unscheduled in US,
but subject to Federal Analog Act
(methcathinone)
61
Methylone
(3,4-methylenedioxy-N-methylcathinone)
 
 
 
 
Synthetic stimulant and entactogen
“M1”, “Explosion”, “bk-MDMA”
Appeared in 2004 in Netherland in
headshops as a “room odorizer”. Label
states “Room odorizer Vanilla, do not
ingest” and “Never use more than one
bottle”
Reported dosages range from 100 to
250 mg to produce euphoric
stimulating effect similar to those of
MDMA
62
Methylenedioxypyrovalerone
 
 
 
 
 
Psychedelic stimulant
“MDPV”, “MDPK”, “Magic”, “Super Coke”, “PV”
Marketed in US as “bath salts” under such
names as Pixie Dust, Ivory Wave, Ocean,
Charge Plus, White Lightning
Reported dosages range from 5 to 20 mg and
produces effects similar to cocaine and
amphetamines
Extended binges on MDPV have been reported
to produce a severe “comedown” syndrome
similar to methamphetamine
63