by B Zedeck
61
the blood-brain barrier. Any benzoylecgonine in brain is from
cocaine metabolism therein. The half-life of cocaine is about one
hour, but the half-life of benzoylecgonine is about five to seven
hours. Cocaine is excreted in urine for about 10 hours, while
benzoylecgonine can be found in urine as soon as one hour after
use and for about three days thereafter. Urine drug screens test
for this metabolite. If benzoylecgonine is detected in urine, use
of cocaine occurred within the past 72 hours. Cocaine has also
been found in breast milk. It passes the placental barrier, and
there is some evidence that it causes fetal abnormalities. When
both cocaine and alcohol are used at the same time, the two are
metabolically combined to form cocaethylene, a compound as
active as cocaine but with a longer half-life. Even though alcohol
may no longer be detected, finding cocaethylene suggests that the
individual may have been under the influence of both substances
at the same time.
Methamphetamine
Methamphetamine passes the blood-brain barrier better than
amphetamine, and there is evidence that chronic use of meth-
amphetamine can result in permanent damage to dopamine
neurons. Both pass the placental barrier, and there is some
evidence that abuse by a pregnant woman can result in fetal
abnormalities. Methamphetamine is found in breast milk. The
half-life of methamphetamine and amphetamine is about 10 to
13 hours. Some methamphetamine is metabolized to amphet-
amine, and amphetamine-glucuronide can be detected in urine
for about two days. About 50% of methamphetamine is excreted
unchanged in the urine over two to three days.
Cathinone
After chewing khat leaves, it can take up to two hours to achieve
peak levels of cathinone. The half-life is about 4.5 hours.
62 Forensic Pharmacology
Cathinone is metabolized to norephedrine and norpseudo-
ephedrine. Cathinone is found in breast milk. Babies of mothers
who used khat have low birth weights. Methcathinone acts like
methamphetamine, and effects last four to six hours.
Most of the CNS stimulants induce similar psychological
effects, including euphoria, an increased sense of strength and
self-confidence, and sexual arousal. After the euphoric effect, a
dysphoria follows, in which the individual feels restless, anxious,
and depressed, and wants to repeat the experience. The drugs
adversely affect judgment and decision making, and impair
psychomotor functions. Physiologically, they increase heart rate,
blood pressure, body temperature, and respiratory rate. The
drugs also affect visual acuity by causing dilated pupils. High
doses can lead to seizures, strokes, and cardiac arrhythmia. The
latter can lead to sudden death. Prolonged use can result in per-
sonality changes, psychosis, hallucinations, paranoia, fatigue,
weight loss, tremors, and depression. Cocaine use creates the
sensation that bugs are burrowing under the skin, and longtime
users can damage their skin through scratching. Tolerance may
develop more with amphetamines than with cocaine; with-
drawal signs and symptoms include depression, lethargy, and
anxiety and sleep disorders.
FORENSIC ISSUES
The presence of cocaine or benzoylecgonine in blood, urine,
hair, or other tissues is indicative of cocaine usage. No other
known substance can give rise to a false positive, and there are
no legitimate excuses to account for a positive result. There are
many reports of hospitalized infants and children with positive
urine test results indicative of exposure to cocaine. The most
likely route of exposure was secondhand smoke in homes where
crack cocaine was used.
Central Nervous System Stimulants
63
In murder cases, high blood levels of cocaine or metabolites
have sometimes served to argue on the defendant’s behalf. If a
murdered person was shown to have used cocaine, the defendant
could argue that the killing was done in self-defense. If the defen-
dant was the one who had used cocaine, the defense attorneys
could argue that the defendant did not have the mental ability to
form intent for murder.
In one actual case, a man and his girlfriend had a fight, dur-
ing which the girlfriend stabbed the man and he died. She was
charged with murder. Toxicological analysis of bodily samples
from the deceased revealed the presence of alcohol in both
blood and brain at a concentration of 0.19%, and the presence of
cocaine; benzoylecgonine, the metabolite of cocaine; and coca-
ethylene, the metabolite of alcohol plus cocaine. At trial, in sup-
port of an argument for self-defense, testimony emphasized the
adverse effects of alcohol, cocaine, and cocaethylene on behavior
and judgment. The woman was acquitted of murder.
In another case involving alcohol and cocaine, the defendant
shot three police officers and was charged with attempted mur-
der. The defendant claims that he had no memory of the events.
Urine analysis indicated the use of cocaine. Testimony at trial
emphasized the adverse effects of cocaine on behavior and on the
inability to form intent to kill. In this case, however, the man was
found guilty and sentenced to 60 years to life.
In actual cases involving random employee urine tests that
were positive for cocaine metabolite, people have offered many
different ways of explaining the test results. For example, one
person proposed that cocaine was put in his medication capsules,
another that cocaine was added to her drink at a party, another
person claimed that she inhaled cocaine as secondhand smoke
while looking for someone in a crack house, and a garbage col-
lector claimed that garbage bags had ripped open and covered
him with white powder. Other explanations offered in defense
64 Forensic Pharmacology
were that urine samples were mixed up at the collection center or
there were other errors related to chain-of-custody, the sequence
of steps from point of collection to the reporting of results. These
arguments have almost never been successful, and the individu-
als have had to resign from employment.
A positive screening test result for amphetamines may be
due to use of amphetamine or methamphetamine-containing
prescription or over-the-counter drugs. For example, the drug
Selegiline, which is used to treat Parkinson’s disease, is metabo-
lized to amphetamine and methamphetamine. The nasal decon-
gestant pseudoephedrine can cross-react in the test and result
in a false positive. In the latter case, the confirmatory test is for
amphetamine.
Figure 6.4 Methamphetamine that is manufactured illegally is
usually a crystalline solid known as crystal meth or crystal.
Central Nervous System Stimulants
65
Vicks vapor inhaler, a decongestant, contains l-metham-
phetamine, listed on the container as levmetamfetamine. Use of
this product results in only l-amphetamine appearing in urine.
If d-amphetamine is detected in urine, it could only have come
from using d-methamphetamine or d-amphetamine-containing
legal or illegal drugs.
Many people prepare methamphetamine in their homes (Fig-
ure 6.4), placing both themselves and their families in peril.
Oregon has already passed legislation requiring a prescription for
any cold and allergy medication containing pseudoephedrine,
the chemical used to make methamphetamine. Congress has
passed a law requiring that pseudoephedrine-containing prod-
ucts be sold only from behind the pharmacy counter.
SUMMARY
Drugs that stimulate the CNS cause euphoria and an increased
sense of self-confidence, strength, and sexual arousal.
Physiological responses include an increase in heart rate, blood
pressure, temperature, and respiratory rate. The drugs act pre-
dominantly by increasing the synaptic levels of dopamine and
norepinephrine. This class of drugs induces predominantly
psychological dependence rather than physical dependence.
Withdrawal signs and symptoms consist of dysphoria and
restlessness.
7
Central
Nervous System
Depressants
Central nervous system (CNS) depressants include alcohol,
barbiturates, benzodiazepines, gamma-hydroxybutyrate (GHB),
chloral hydrate, glutethimide, and methaqualone.
THE HISTORY OF DEPRESSANTS
There is evidence that the Greeks, Egyptians, Hebrews, Japanese,
Chinese, and Russians made alcoholic beverages thousands of
years ago. Alcohol (ethanol, ethyl alcohol, and grain alcohol) is
produced by yeast fermentation of sugar in fruits and grains to
make wine, beer, or a variety of alcoholic spirits, including gin,
vodka, and scotch.
The German chemist Adolph Von Bayer prepared barbitu-
rates in the 1860s. The first barbiturate, barbital (Veronal), was
marketed in 1903, and phenobarbital (Figure 7.1) was introduced
in 1912. Barbiturates used to be common drugs of abuse in the
1950s and 1960s, but because of their dependence-inducing
properties and association with suicides and accidental deaths,
their use has been reduced significantly.
66
Central Nervous System Depressants
67
Figure 7.1 Phenobarbital is a barbiturate with the chemical formula
C12H12N2O3.
In the 1930s, Dr. Leo Sternbach discovered benzodiazepines,
and in 1954, he developed Librium, the first “tranquilizer,” an
ambiguous term that is no longer used. Though many people
suffered serious side effects and developed drug dependence to
benzodiazepines, these problems were not openly acknowledged
until the late 1970s. Benzodiazepines are still the most commonly
prescribed mood altering drugs, seen as alternatives to barbitu-
rates to treat anxiety, muscle tension, and sleep disorders.
Dr. Henri Laborit synthesized gamma-hydroxybutyrate
(GHB) in France in 1960 for use as an anesthetic, based on
its chemical similarity to gamma-aminobutyric acid (GABA).
Since it does not block out pain, use of GHB did not become
widespread. It was discovered in the late 1970s that GHB could
stimulate the release of growth hormone, and, although contro-
versial, body builders and weight lifters began using it with the
goal of reducing fat and increasing muscle mass.
68 Forensic Pharmacology
PHARMACOLOGY OF CNS DEPRESSANTS
CNS depressants inhibit nerve activity, leading to decreased
anxiety, sedation, uncoordinated movements, and, if the dose
is high enough, unconsciousness and even death. Sometimes,
however, the inhibition of nerve activity occurs in a pathway
that normally inhibits our actions, causing the opposite effect
of disinhibition, in which intoxicated people say and do things
they normally would not.
Alcohol
Alcohol, taken orally, is absorbed in the stomach but mostly
from the small intestine into the bloodstream. It first reaches the
liver, where some alcohol is immediately metabolized (first-pass
metabolism) by the enzyme alcohol dehydrogenase. Alcohol is a
water-soluble chemical and distributes throughout body fluids
but not readily into body fat. Females, who naturally have more
lipid (fat) tissue per pound of mass, will have a higher BAC than
males after consuming the same amount of alcohol.
There are 9.6 grams of alcohol in 1 ounce (30ml) of 80-proof
(40% alcohol) hard liquor, 13.4 grams of alcohol in one 12-ounce
can of beer (average alcohol content of 4.67%), and 11.4 grams
of alcohol in a 4-ounce glass of wine (average alcohol content of
12%). A 150-pound male who consumes one can of beer over a
short time period will have a BAC of approximately 0.029%. A
150-pound female who consumes one can of beer over the same
time period will have a BAC of approximately 0.036%.
Though the rates of metabolism and excretion of many drugs
are measured in terms of half-lives, the elimination of alcohol
primarily by liver enzymes occurs as a constant amount per time
regardless of its concentration. On average, the BAC decreases
0.015% per hour. Thus, it would take about five hours before
someone’s BAC reached zero if he or she consumed enough
alcohol to have reached a BAC of 0.075%. Also, if one consumed
Central Nervous System Depressants
69
only one drink per hour, it would require many hours before
a significant BAC would accumulate. Since alcohol is volatile,
some is excreted via the breath with each exhalation. This is the
basis for the breath test (see Chapter 3). Alcohol is also excreted
in urine, saliva, and sweat.
There is a relationship between BAC and alcohol’s effects.
Basically, a BAC of up to 0.05% results in little impairment, but
with a BAC between 0.05% and 0.10%, some impairment of cog-
nitive functions, such as attention span, information processing,
and judgment, is seen. The individual begins to feel euphoric,
talkative, show increased confidence, and exhibit a loss of inhi-
bitions. There is a loss of fine motor coordination. Alcohol also
inhibits the release of antidiuretic hormone from the pituitary
gland. This causes diuresis, and explains the necessity of hav-
ing to urinate after consuming alcoholic beverages. A BAC over
0.10% usually causes ataxia (unsteady balance), slurred speech,
impaired memory, comprehension, and perception, and vomit-
ing. Alcohol-induced blackouts, that is, a total amnesia of events
that can never be recalled, usually occur at a BAC of around
0.28%. As alcohol is metabolized and eliminated, the individual
returns to a normal state. Large enough doses can produce stu-
por, coma, and death.
Alcohol is toxic to the liver, and prolonged use results in cir-
rhosis, a condition in which scar tissue replaces normal liver
tissue, and impairs the ability of the liver to function. Chronic
use can also result
in permanent damage to the CNS, partly due
to a poor diet regimen and diminished intake of vitamin B1
(thiamine).
Barbiturates
Barbiturates are used as sedatives, hypnotics, anesthetics, and
anticonvulsants. They differ in how fast they produce effects
and how long the effects last. Barbiturates are classified as
70 Forensic Pharmacology
ultrashort, short, intermediate, and long acting, and are in
Schedules II, III, or IV.
Street names of commonly abused barbiturates describe the
color and markings on the actual pill. Amytal® (amobarbital):
blue heavens; Butisol® (butabarbital): bute, stoppers; Lumi-
nal® (phenobarbital): phennies and phenos; Nembutal® (pento-
barbital): nembies and yellow jackets; Seconal® (secobarbital):
red devils and seggies; Tuinal® (amobarbital and secobarbital):
Christmas trees, rainbows, tooies. Other street names include
amy’s, block busters, bluebirds, downers, goofballs, pinks, and
stumblers.
The Derivation of Proof
The term proof used for alcoholic beverages dates back to
colonial days in the United States. President George Washing-
ton appointed Alexander Hamilton as his first secretary of the
treasury. Hamilton levied a 10-cents/gal on tax on whiskey.
The citizens of Pennsylvania—a chief source of whiskey—
rebel ed, but their famous “Whiskey Rebel ion” was sup-
pressed. To determine the content of alcohol in the whiskey,
gunpowder was moistened with the alcohol-containing prod-
uct and then ignited. If the alcohol content was high enough,
the product burnt, and this was considered 100 proof. At least
50% alcohol was required for the gunpowder to burn. The gov-
ernment said that 100 proof, or 50% alcohol by volume, was to
be the standard for American liquor. Yet, the 10-cents/gal on
tax was placed on all whiskey, even if below proof. Today, the
proof number is always twice the percentage number of the
concentration of alcohol in the product.
Central Nervous System Depressants
71
Barbiturates are usually taken orally, sometimes with alco-
hol to increase the intoxicating effect, or by injection. The
ultrashort-acting barbiturate Pentothal® produces surgical
anesthesia within about one minute after intravenous admin-
istration. The onset of action of the short- and intermediate-
acting barbiturates taken orally for insomnia is from 10 to 60
