Forensic Pharmacology
Page 10
rences of certain aspects of a person’s LSD experience, without
the user having taken the drug again. A flashback occurs sud-
denly, often without warning, and may occur within a few days
PiHKAL and TiHKAL
Alexander “Sasha” Shulgin received his Ph.D. in biochemistry
from the University of California, Berkeley. His research inter-
ests are in psychiatry and pharmacology. A student aroused
his interest in MDMA, and in the late 1970s and early 1980s,
Shulgin introduced MDMA to psychologists for use in their
patients. Shulgin synthesized and tested on himself, and on a
small group of friends, hundreds of psychoactive chemicals.
Shulgin and his wife Ann collected the entire chemical syn-
thetic data and descriptions of effects, and published several
books including PiHKAL (Phenethylamines I Have Known and
Loved): A Chemical Love Story and TiHKAL (Tryptamines I Have
Known and Loved): The Continuation.
Hallucinogens
95
or even years after LSD use. Dysphoric effects following use of
hallucinogens include sadness, anxiety, memory impairment,
and depression.
FORENSIC ISSUES
Each dose of LSD (about 0.05 mg) is too small to be sold and
administered separately. A solution of LSD is applied to a carrier,
such as paper, which is then cut up into individual portions. A
person convicted of distributing LSD is sentenced according to
the entire weight of material seized, including the carrier. Since
carriers may be of different weights, the same number of doses
of LSD may carry different sentences. Although recognizing the
unfairness of this law, the Supreme Court ruled that the weight
of LSD does include carrier and that it is up to Congress to
change the statute.
In one actual case, a man used LSD and, within an hour there-
after, killed a store owner. The defendant claims that he awoke
one morning and took five to six Fioricet® tablets, went out and
purchased two bags of heroin, and took cocaine hourly for five
hours. Then, for the first time in six years, he took six “hits” of
LSD. His memory afterward was vague, until he realized that
he was in police custody. He apparently entered a store, had an
argument with the owner, and killed him. People witnessing the
events captured and held the defendant until the police arrived.
The man was found guilty of murder.
SUMMARY
There are two main chemical categories of hallucinogens: the
indolealkylamine derivatives, which are related to the neurotrans-
mitter serotonin, and the phenethylamine derivatives, which
96 Forensic Pharmacology
are related to norepinephrine and dopamine. Hallucinogens
alter the senses affecting sight, sound, touch, taste, and smell.
They induce vivid images and sounds, profound emotional epi-
sodes, altered perceptions of time and space, out-of-body expe-
riences, and, if doses are high enough, convulsions. Tolerance
does develop. There is some evidence that ecstasy can cause
irreversible damage to serotonin neurons. Effects usually begin
within minutes and can last for many hours. With LSD, flash-
backs of prior experiences can occur without the user having
taken more of the drug.
Dissociative
Anesthetics
10
Dissociative anesthetics induce analgesia in patients who are
conscious but feel removed from their surrounding environment.
The two prominent dissociative anesthetics are phencyclidine
(PCP) and ketamine. PCP is a synthetic drug first prepared in
1926 and tested as a general anesthetic for surgical patients in the
late 1950s under the trade name of Sernyl®. Although anesthe-
tized, patients given phencyclidine remained conscious, staring,
and rigid, without depression of respiration or cardiovascular
function. Following surgery, however, patients became deliri-
ous, disoriented, and unmanageable, and phencyclidine testing
was discontinued. Until 1978, the drug was still used legally
for veterinary anesthesia under the name Sernylan®. In the late
1960s, PCP became popular as a street drug in San Francisco
and was termed the “peace pill.” In spite of reports of “bad trips”
and violent behavior, its popularity increased during the 1970s
and 1980s. Though illicit use of PCP declined with the rise of
cocaine use in the 1980s, it now appears to be increasing.
Street names for PCP include angel dust, cadillac, CJ, crystal,
dust, elephant tranquilizer, embalming fluid, hog, jet fuel, juice,
killer weed, love boat, Peace, PeaCePill, rocket fuel, sherms
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98 Forensic Pharmacology
Figure 10.1 Drug enforcement agents in the Phillipines surround
confiscated bags and vials of ketamine after an apartment raid in May
2005. The drugs had an estimated street value of $150,000 U.S. dollars.
In powdered form, ketamine has an appearance similar to cocaine but
a vastly different pharmacology.
Dissociative Anesthetics
99
(using cigarettes produced by Nat Sherman Tobacco Company
for dipping into liquid PCP), whack, and zoom. When used in
combination with embalming fluid (which contains formalde-
hyde, methanol, and ethanol), it is known on the street as wets,
illy, and fry. It is also used in combination with heroin, LSD, and
marijuana. The combination with marijuana is termed killer
joints, crystal supergrass, or, in Spanish, yerba mala. PCP is listed
in Schedule II.
Calvin Stevens developed ketamine while working at Parke-
Davis in 1961. It is used as a veterinary and human anesthetic,
and is a Schedule III drug. It was widely used as a field anesthetic
in the Vietnam War, and it entered the rave scene in the early
1990s. Ketamine has been used as a date rape drug. Street names
include baby food, cat Valium, honey oil, jet, K, keets, ket, special
K, super acid, super C, and vitamin K (Figure 10.1). Trade names
are Ketalar®, Ketajet®, and Ketaset®.
PHARMACOLOGY OF PCP AND KETAMINE
Both PCP and ketamine can be used as a liquid or solid and can
be injected, ingested, snorted, or smoked when sprinkled on
marijuana or parsley leaves. Heat destroys much of the drug.
Peak blood levels occur within 15 minutes after smoking.
The effects last for approximately 4 hours, although it may take
more than 24 hours for an individual to return to a normal state.
The drugs are stored in fatty tissue and released slowly. PCP has
a long half-life ranging from many hours to days, and the PCP
glucuronide metabolite can be found in urine for several days or
weeks. PCP is found in breast milk. The half-life of ketamine is
three to four hours, and metabolites of ketamine are excreted in
urine. PCP and ketamine cross the placental barrier, and infants
of chronic abusers have been born with cerebral palsy, facial
deformities, and behavioral abnormalities.
100 Forensic Pharmacology
PCP and ketamine bind to the NMDA receptor
and block
the neurotransmitter glutamate. PCP also blocks reuptake of
dopamine, norepinephrine, and serotonin. Because so many
neurotransmitters are affected, the signs and symptoms of PCP
intoxication are numerous and varied.
The acute behavioral effects of PCP and ketamine include
euphoria, distortion of the senses and of time, impaired judg-
ment, anxiety, sedation, analgesia, dizziness, dissociation from
surroundings, amnesia, psychosis, panic attacks, paranoia, vio-
lent behavior, hallucinations, catatonia (a condition character-
ized by bizarre rigid positions and unresponsiveness), coma,
and seizure. People may have thoughts of death and dying,
and are susceptible to suggestion and manipulation. Under the
influence of PCP, individuals have shown very bizarre behavior,
including lying down in traffic, suddenly murdering or raping
family members, and robbing a bank using a broom. Often the
individual cannot recall any of the events.
The physiological effects include an increase in blood pres-
sure and body temperature, nystagmus, slurred speech, ataxia,
blurred vision, excessive sweating and salivation, fast heart rate,
nausea, vomiting, and extraordinary strength. Deaths have been
recorded from heart or respiratory failure.
Tolerance to dissociative anesthetics does develop. Psychologi-
cal dependence is greater than physical dependence, although
withdrawal symptoms may last for several weeks and include
diarrhea, chills, tremor, anxiety, depression, and irritability. Pro-
longed use of PCP may induce permanent learning disabilities,
amnesia, depression, and antisocial behavior.
FORENSIC ISSUES
Examples of actual cases involving PCP include driving while
impaired, murder, kidnapping, robbery, rape, and burglary. In
Dissociative Anesthetics 101
one particular case, a young woman driver struck another car,
and the two occupants were killed. The driver was apprehended
Drug Effects:
Animals Versus Humans
All medication needs to be approved by the Food and Drug
Administration (FDA) before it can be released to the public
in the United States. Many of the pharmacology studies of a
drug’s efficacy and safety are first done on laboratory ani-
mals. This is because there is much similarity in the anatomy,
physiology, and biochemistry of animals and humans, and
there is much experimental evidence showing similarity in
response to many different drugs. Arguments in a lawsuit that
a specific chemical is causal y linked to an individual’s injury
or behavior often use data from animal studies.
However, occasional y there are responses in humans that
are unexpected based upon results from animal studies. The
response to dissociative anesthetics is a good example of one
such difference. Whereas humans exhibit delirium following
treatment with PCP, animals exhibit sedation. Different meta-
bolic pathways or rates of metabolism, and differences in mode
of elimination between animals and humans, might account for
the variation in responses. For example, rats do not have a gall
bladder and dogs sweat minimal y. It is easy to see that choos-
ing the wrong species in animal tests could result in inaccurate
data relevant to humans. Nevertheless, preclinical testing is
necessary, and there is much research today to develop in vitro
in the laboratory) procedures that can predict human in vivo (in
the body) responses. As more of these tests prove to be reli-
able, fewer animals wil be used in research.
102 Forensic Pharmacology
five hours later, and a blood test revealed a significant amount
of PCP. She admitted to smoking PCP about 20 minutes before
the accident. Testimony for the prosecution at both a grand jury
hearing and at the subsequent trial explained PCP pharmacoki-
netics and the effects of PCP on mental functions and coordina-
tion. The defendant was found guilty of vehicular manslaughter
and sentenced to two to six years.
SUMMARY
PCP and ketamine are dissociative anesthetics. They can induce
analgesia without loss of consciousness. The individual appears
awake but will not remember the experience, and vital signs
such as respiration and heart rate are not impaired. The drugs
distort perceptions of sight and sound, and produce feelings of
detachment and dissociation from the environment and self.
Persons abusing PCP exhibit very bizarre behavior and may
become violent.
Inhalants
11
Inhalants of abuse are substances whose volatile vapors can
be inhaled either through the nose or the mouth into the lungs
and then travel to the brain, where they induce euphoria and
mind-altering effects. In the late 1700s, an English chemist,
Joseph Priestley, discovered that nitrous oxide gas has mind-
altering and anesthetic effects, and, in the 1830s, chloroform
was discovered to have anesthetic effects as well. Many of the
volatile solvents, paint thinners, gasoline degreasers, and glues
were abused during World War I and subsequently, but it was
not until 1959 that inhalant abuse was first documented in
the media, in Denver, Colorado, and then use spread to other
cities. Inhalants are common among adolescents and are often
the first drugs of abuse because they are inexpensive, difficult
to detect, and easily available. During 2004, 9.6% of 8th grad-
ers, 5.9% of 10th graders, and 4.2% of 12th graders had used
inhalants.17
Inhalants are found in many commercial products and are
not listed as controlled substances. They can be solvents such as
toluene, found in paint thinner, degreaser, nail polish remover,
gasoline, and glue; propellants such as butane and propane,
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104 Forensic Pharmacology
Figure 11.1 The blood-brain barrier prevents the passage of large
molecules, such as proteins, into the brain. Small molecules, such
as glucose and molecules found in drugs of abuse, are able to pass
through the barrier.
Inhalants 105
used in hair sprays and cooking sprays; gases, including
medical anesthetics such as chloroform and nitrous oxide
(laughing gas, also used as propellant for whipped cream and
inhaled from balloons); and nitrites, including amyl nitrite
and isobutyl nitrite. Many of the inhalants are flammable, and
people who use them can suffer serious burns.
Some street names for inhalants include air blast, hippie
crack, moon gas, poor man’s pot, rush, and snappers. Amyl
nitrite is known as amies, pearls, and poppers. Nitrous oxide
is known as hysteria, laughing gas, NOZ, shoot the breeze, and
whippets.
PHARMACOLOGY OF INHALANTS
Vapors can be inhaled directly from a can, a bag (called “bag-
ging”), a balloon, or an inhalant-soaked cloth (called “huff-
ing”). Inhalants enter the bloodstream through the capillaries
on lung alveoli and, being highly lipid soluble,
easily pass the
blood-brain barrier (Figure 11.1). They interfere with ion
movement in the cell membrane at the glutamate or GABA
receptor, resulting in an inhibition of transmission.
Depending on the dose, inhalants can cause effects ranging
from intoxication to anesthesia. Intoxication can last only a
few minutes or several hours, if inhalants are taken repeat-
edly. Initially, users may feel slightly stimulated, euphoric, and
light-headed. With repeated inhalations, users may feel less
inhibited and less in control, and can hallucinate. Other effects
include headache, muscle weakness, abdominal pain, severe
mood swings and violent behavior, numbness and tingling of
the hands and feet, nausea, and lack of coordination. Inhaling
highly concentrated amounts of chemicals can quickly lead to
arrhythmia, heart failure, and death. This is known as “sud-
den sniffing death.” The nitrites relax smooth muscle causing
106 Forensic Pharmacology
vasodilation and induce flushing, warmth, hypotension, and
dizziness. For example, amyl nitrite is used as a medication
to relieve angina (chest pain caused by lack of blood flow and
oxygen to the heart) by dilating the coronary vessels.
Signs of inhalant abuse are unusual breath odor or chemical
odor on clothing; paint or stain marks on the face, fingers, or
clothing; spots or sores around the mouth; and red or runny eyes
or nose. Other clues include hidden rags or clothing, or empty
containers.
Chronic abuse of inhalants can cause severe, irreversible effects
on the brain, heart, liver, lungs, kidneys, and blood, and can
result in hearing loss, limb spasms, cognitive impairment, and
various psychological and social problems. Inhalants damage
the peripheral nerves, leading to muscle weakness and paralysis,
and damage the nerve fibers in the CNS. Inhalant abuse during
pregnancy can cause spontaneous abortion, premature delivery,
and fetal abnormalities such as low birth weight, small head size,
facial abnormalities, and muscle tone abnormalities similar to
those occurring in fetal alcohol syndrome.
Nitrous oxide can react with vitamin B12, preventing its use
in red blood cell development and resulting in anemia. Use of
nitrites can rapidly result in fatal methemoglobinemia, a condi-
tion that reduces the ability of the blood to transport oxygen. In
1944, 11 men were admitted to a New York hospital with bluish