by B Zedeck
minutes, and the effects last up to six hours. Barbiturates dis-
tribute to body fat and are found in breast milk. They may cause
drowsiness, slow heartbeat, and shortness of breath in babies of
nursing mothers who are taking these drugs.
Barbiturates are metabolized in the liver via hydroxylation and
glucuronide conjugation. Short-acting barbiturates are excreted
in the urine as metabolites for about one to four days, while long-
acting barbiturates are excreted for two to three weeks.
Barbiturates overdosing may occur readily. Since tolerance
develops to the behavioral effects but not to the respiratory
effects, increasing the dosage may result in death. Also, because
of amnesia-causing effects, people forget that they took their
medication and may proceed to take additional doses, which may
lead to respiratory depression and death.
Benzodiazepines
Trade names of some benzodiazepines are Ativan® (lorazepam),
Dalmane® (flurazepam), Halcion® (triazolam), Klonopin®
(clonazepam), Librium® (chlordiazepoxide), Restoril® (temaze-
pam), Serax® (oxazepam), Valium® (diazepam), Versed®
(midazolam), and Xanax® (alprazolam). Some street names
include benzos, downers, and goofballs. The “date rape drug”
Rohypnol® (flunitrazepam) has its own group of names, includ-
ing forget-me pill, Mexican valium, mind erasers, R2, roches,
roofies, rope, and rophies (Figure 7.2). Except for Rohypnol®,
which cannot be sold in the United States, the benzodiazepines
are listed as Schedule IV drugs.
72 Forensic Pharmacology
Figure 7.2 Photographed above is a box of Rohypnol tranquillizer
pills, powerful sedatives normally prescribed as sleeping pills for
insomniacs, which have unfortunately gained notoriety as a “date
rape” drug. Rohypnol causes sleepiness and memory loss when
dissolved in an alcoholic drink; therefore, a blue dye has been added
to the pills to prevent this from occurring unnoticed.
Benzodiazepines are grouped into categories depending on
how fast they take effect and how long the effects last. The short-
acting benzodiazepines flurazepam, temazepam, and triazolam
are used to manage insomnia, and the long-acting alprazolam,
chlordiazepoxide, diazepam, lorazepam, and clonazepam are
used for the treatment of generalized anxiety.
Benzodiazepines are lipid soluble and are found in breast
milk. They are metabolized in the liver and excreted as glucuro-
nide metabolites at different rates. For example, the half-life of
triazolam is 2 to 5 hours, while that of diazepam varies between
Central Nervous System Depressants
73
20 and 100 hours, and that of an active metabolite of diazepam
(desmethyldiazepam), between 36 and 200 hours. This means
that diazepam metabolites may be in the bloodstream up to
200 hours after a single dose. Many of the benzodiazepines are
converted to the same active metabolite. For example, diaz-
epam, temazepam, and chlordiazepoxide are all metabolized to
oxazepam.
Gamma-hydroxybutyrate
GHB, a Schedule I drug, is synthesized by mixing gamma buty-
rolactone (GBL; street names: blue nitro, fire water, gamma G)
and sodium hydroxide. GBL is a solvent in many commercial
products and is not listed as illegal. If ingested, GBL is rapidly
converted in the body to GHB. Another solvent, 1,4 butanediol
(BD) (street names: Sucol B, zen), is metabolized in the body to
GHB. GHB is a natural metabolite of GABA.
GHB is used to treat cataplexy, a sudden onset of muscle weak-
ness, in narcolepsy patients. It has been used as a hypnotic, anes-
thetic, and aphrodisiac, and is used to treat alcohol withdrawal.
Some street names include cherry meth, eclipse, EZ lay, fantasy,
G, Georgia home boy, great hormones at bedtime, grievous
bodily harm, liquid ecstasy, nature’s Quaalude, and poor man’s
heroin (Figure 7.3). According to a 2004 NIDA survey, 0.7% of
eighth graders, 0.8% of tenth graders, and 2.0% of twelfth grad-
ers used GHB at least once during the preceding year. In 2002,
there were 3,330 emergency room admissions related to GHB,
second only among club drugs to the hallucinogen methylene-
dioxymethamphetamine (MDMA).13
GHB used orally is rapidly absorbed, and peak effects occur
in 20 to 40 minutes. The effects last for about three hours. The
half-life is approximately 20 minutes. About 5% of the dose is
eliminated in urine, mostly in the first four hours. Since GHB
is odorless and tasteless, it can be added to someone’s drink
74 Forensic Pharmacology
without detection. It causes a rapid induction of deep sleep and
amnesia, and is used as a date rape drug. GHB is a common
drug at rave parties.
Barbiturates, benzodiazepines, and GHB affect the activity
of the neurotransmitter GABA, resulting in more chloride ions
entering the neuron and making it more resistant to excitation.
As a consequence, the output of excitatory neurotransmitters,
including norepinephrine (noradrenaline), serotonin, and dopa-
mine, is reduced.
Figure 7.3 Gamma-hydroxybutyrate (GHB) is manufactured in illicit
home laboratories. The chemicals above were confiscated from a GHB
lab in Germany.
Central Nervous System Depressants
75
Other CNS Depressants
Chloral hydrate, glutethimide, and methaqualone also produce
a depressant effect. Chloral hydrate is dangerous to use as an
anesthetic, but it has been used to treat persons undergoing
withdrawal from heroin, GHB, and alcohol. A mixture of chlo-
ral hydrate and alcohol is termed a “Mickey Finn” and has been
used as a date rape drug.
Glutethimide (Doriden®) was introduced in 1954 as a substi-
tute for barbiturates. Its street names include CB, glue, and goof-
balls. The combination of glutethimide and codeine is called
“doors and 4s” and “pancakes and syrup.” The combined eupho-
ria resembles that of heroin, and effects can last for about eight
hours.
Methaqualone was marketed by William H. Rorer, Inc., under
the trade name of Quaalude, and later by the Lemmon Company
as Lemmon “714” tablets. Street names include bandits, drunken
monkey, ludes, magwheels, quay, 714, sopors, and wagon wheels.
Methaqualone was used during the 1960s and 1970s on many
college campuses, and there were many reports of overdoses and
deaths. The use of methaqualone has diminished greatly since
the late 1980s.
Though some differences between CNS depressant drugs do
exist, as a group the effects induced are very similar. They cause
a state of intoxication, with signs and symptoms of euphoria,
mental confusion, loss of motor coordination, blurred vision,
slurred speech, nausea, vomiting, impaired judgment, decreased
attention span, and amnesia. The drugs also decrease blood pres-
sure, heart rate, and respiration.
Tolerance and psychological and physical depe
ndence do
develop. Withdrawal effects from CNS depressants include anxi-
ety, tremors, sweating, sleep disturbances, nausea, vomiting,
and headache. Hallucinations and seizures are possible. Dosage
must be reduced gradually. A condition specific to the effects of
76 Forensic Pharmacology
alcohol is delirium tremens. This may begin as late as 14 days
after cessation of alcohol consumption. The signs and symptoms
include confusion, delusions, fever, sweating, increased blood
pressure, and seizures. Withdrawal effects can be treated symp-
tomatically with benzodiazepines, antiseizure medication, and
nutritional supplements.
All of the CNS depressants can pass through the placenta.
Newborn babies with dependent mothers may be physically
dependent themselves and have withdrawal symptoms that
include tremors, irritability, hyperactivity, and feeding and
breathing problems. There may be birth defects such as fetal
alcohol syndrome, which consists of abnormal facial features, a
small head, mental retardation, and poor coordination.
Combined use of any of the drugs in this category increases
the risk of death. While a single drug may not depress respiration
markedly, a combination of drugs can do so. The antidote for
benzodiazepine overdose is an intravenous injection of Romazi-
con® (flumazenil).
FORENSIC ISSUES
In the 1970s, Marcelline Burns and Herbert Moskowitz set out
to standardize field sobriety tests. They selected 10 psychophysi-
cal tests in use at that time and, along with the Los Angeles
police and sheriffs departments and the California Highway
Patrol, tested each for accuracy in predicting whether a person
had a BAC of 0.10% or higher. Of the 10 different tests, the one-
leg stand, the walk-and-turn test, and the horizontal gaze nys-
tagmus test proved to be of value in detecting lack of sobriety.
These three tests, under the sponsorship of the National High-
way Traffic Safety Administration (NHTSA), were further devel-
oped under experimental conditions and under field conditions.
It was found that if one failed the one-leg-stand test, the officer
Central Nervous System Depressants
77
would be correct 65% of the time in stating that the person’s
BAC was above 0.10%; if the walk-and-turn test was failed, the
officer would be accurate 68% of the time; and if the horizontal
gaze nystagmus test was failed, accuracy would be 77%. If both
horizontal gaze nystagmus and the walk-and-turn tests were
failed, accuracy increased to 81%.14 All states have established a
BAC of 0.08% as the cutoff value for determining driving while
intoxicated, or DWI.
Examples of actual cases involving alcohol include DWI,
motor vehicle accidents (involving alcohol in either pedestrian
or driver), rape, personal injury (tripping or falling), burglary,
theft, assault, and attempted murder. In many cases, it was nec-
essary to calculate the BAC at the time of the accident or other
event that had occurred hours before the breath or blood sample
was taken (a process known as “back extrapolation”).
In one particular case, a young man attacked a public figure
with a knife. He was immediately apprehended and charged with
attempted murder. At trial, testimony revealed that during the
previous 24 hours, the man had consumed enormous amounts
of alcohol and had used marijuana. The defense argued that this
amount of alcohol plus marijuana had impaired the defendant’s
judgment and perception, and that he could not have been able
to form the intent to kill. Testimony involved the pharmacology
of both drugs, calculation of the BAC at about 0.40%, and the
effect of both drugs on the defendant’s mental capabilities. The
jury returned a verdict of guilty of assault and weapons posses-
sion, but not attempted murder. The man was sentenced to 5 to
15 years.
In some states, lawsuits known as “dram shop” cases arise
when someone injured by a driver under the influence of alco-
hol sues the bar or restaurant that had earlier served alcohol to
the driver while the latter was visibly intoxicated. Testimony in
those cases focused on the number and type of drinks served, the
78 Forensic Pharmacology
interval of drinking, when the last drink was served, the time of
the accident, and the rate of alcohol metabolism.
The barbiturate butalbital is sold in combination with aspi-
rin or acetaminophen (Fiorinal® or Fioricet®, respectively) for
treatment of migraine and chronic tension headaches. When
providing a urine sample, consumption of either of these drugs
must be mentioned.
The benzodiazepine Rohypnol® has a rapid onset of action
and has been used as a date rape drug. The victim will have no
memory of any events that occurred while under the influence
of the drug. The effects begin in about 20 to 30 minutes and peak
in about two hours.
GHB can be formed from GABA and is found naturally in
human tissues. In non-GHB users, however, GHB is usually not
detected in blood or urine samples. Also, since GHB appears to
form in blood postmortem, a finding of GHB is not indicative
of use unless there is evidence of oral intake. Because of its short
half-life, GHB is not found in blood 8 hours after use or in urine
after 24 hours. However, lack of GHB after these intervals is not
indicative that GHB was not used in an alleged rape. There are
many reports of GHB being involved in overdoses, motor vehicle
accidents, and deaths.
SUMMARY
CNS depressants are drugs that decrease brain activity, result-
ing in both behavioral and physiological changes. The effects
of alcohol on coordination, speech, and cognitive functions are
familiar to most people. The effects of barbiturates are similar
to alcohol. In low doses, barbiturates act as sedatives: increased
doses have a hypnotic or sleep-inducing effect; and still larger
doses have anticonvulsant and anesthetic activity, and can lead
to respiratory depression, coma, and death. Barbiturate addicts
Central Nervous System Depressants
79
must be withdrawn from the drug gradually to avoid severe with-
drawal symptoms such as convulsions. The benzodiazepines,
introduced as alternatives to barbiturates to manage insomnia
and anxiety, can also induce amnesia and have been used as date
rape drugs. GHB, which causes an alcohol-like effect and amne-
sia, is found at rave parties and has been used as a date rape drug.
Tolerance and psychological and physical dependence develop
to CNS depressants.
8
Opioids
There are many different opioids, and this chapter will focus
on a few that are most commonly abused. Opium is the milky
latex that seeps out of cuts made into the unripe seed capsule
of the poppy plant, Papaver somniferum (Figure 8.1). Opium
contains two pharmacologic groups of chemicals: the phen-
anthrenes, which includes morphine, codeine, and theba-
ine; and the benzylisoquinolines, which includes papaverine
and noscapine. The poppy plant grows in Burma, Thailand,
Cambodia, Laos, India, Pakistan, Afghanistan, Turkey, Mexico,
Brazil, and Colombia.
The effects of opium have been known as far back as 3,000
b.c. In 1803, the German pharmacist Frederick Sertürner iso-
lated morphine from the poppy plant. He named the drug
morphine after Morpheus, the Greek god of dreams, and, in
1832, codeine was isolated. Heroin was synthesized in 1874.
Many years ago, these drugs were termed narcotics, because
of their ability to produce sleep. Today, the word narcotic is
sometimes used incorrectly to denote all drugs of abuse. The
natural opium-derived drugs are more correctly termed opi-
ates, and together with other natural (opioid-like endorphin
80
Opioids
81
Figure 8.1 Opium is collected by slitting the seed capsule of an
unripe opium poppy. A milky substance containing opium oozes out
and soon hardens. The hardened substance is then scraped off and
purified.
82 Forensic Pharmacology
peptides present in brain tissue) and synthetic drugs that have
morphine-like activity, are called opioids. Opioids are used for
their analgesic (pain relief), antidiarrheal, and antitussive, or
cough suppressant, effects.
There are many synthetic derivatives of morphine and codeine
in use today medicinally, including hydrocodone (Hycodan®
and Vicodin®), hydromorphone (Dilaudid®), and oxycodone
(Percodan®, Percocet®, and OxyContin®, a controlled-release
form with street names of hillbilly heroin and poor man’s
heroin). Other compounds that have morphine-like activ-
ity include meperidine (Demerol®), methadone (Dolophine®,
synthesized in Germany during World War II because of a
shortage of morphine), propoxyphene (Darvon®; street names
include pink ladies and pumpkin seeds), and fentanyl (Dura-
gesic®, also known as Apache, China white, goodfellas, mur-
der 8, and Tango and Cash). A designer drug variation of
fentanyl, called 3-methylfentanyl, is 6,000 times more potent
than morphine. Dextromethorphan is an antitussive available
over the counter in many products, including Coricidin HBP®,