Forensic Pharmacology
Page 9
Dimetapp®, Sudafed® preparations, and Robitussin-DM®. Its
street names include candy, CCC (or Triple C, for Coricidin
Cough & Cold), DM, DXM, and Robo. Use of Robitussin-DM®
is termed “Robo-copping” or “Robo-tripping,” and use of Cori-
cidin is termed “skittling.”
Some street names for morphine are cube juice, hard stuff,
hocus, M, Miss Emma, monkey, and white stuff. Names for
opium includes big O, black stuff, Chinese tobacco, Dover’s
powder, joy plant, and zero. Street names for heroin include
dope, H, horse, junk, skag, and smack. The mixture of heroin
and cocaine is termed a speedball. Names for codeine include
Captain Cody, Cody, and schoolboy, and it is found in combi-
nation with glutethimide.
Opioids
83
Heroin is a Schedule I drug; morphine, codeine, fentanyl,
hydrocodone, hydromorphone, and oxycodone are Schedule
II drugs; codeine plus aspirin or acetaminophen is Schedule
III; propoxyphene is Schedule IV; and codeine sold over the
counter is Schedule V.
PHARMACOLOGY OF OPIOIDS
Depending on the type, opioids can be injected, smoked,
snorted, or taken orally. Smoking heroin is termed “chas-
ing the dragon.” Controlled-release oral tablets of morphine
(MS-Contin®) or of oxycodone (OxyContin®) should never
be crushed or chewed, as the entire dose of opioid released at
once may be toxic.
Oral opiates are absorbed well from the intestinal tract.
Morphine, however, is significantly metabolized via first-
pass metabolism and is excreted via enterohepatic circula-
tion. Heroin crosses the blood-brain barrier much more
efficiently than morphine, resulting in a greater effect
(Figure 8.2). Opioids are distributed to many organs and
are found in breast milk. They cross the placenta, and
infants born to mothers who abused opioids during preg-
nancy show signs of dependence and withdrawal. About
10% of codeine is demethylated to produce morphine that
is responsible for codeine’s analgesic effect. The half-life of
morphine, codeine, and heroin is two to four hours. Only
about 10% of morphine is excreted in urine unchanged, and
heroin, morphine, oxycodone, and codeine can be detected
in urine for up to two days after use. Opioids act on sev-
eral receptors, namely, mu (μ), believed responsible for the
“high” as well as for the analgesia, sedation, and depres-
sion of respiration, kappa (κ), delta (δ), and sigma (σ).
84 Forensic Pharmacology
Figure 8.2 Heroin is a derivative of morphine. It can be manufactured
synthetical y by replacing the two hydroxyl (OH) groups in morphine
with two acetate (CH3COO) groups; thus, an alternate name for heroin is
diacetylmorphine.
Dextrorphan, the metabolite of dextromethorphan, blocks
the NMDA receptor.
Behavioral effects of opioids include euphoria, sedation
and mental clouding. Physiological effects include respiratory
depression, decreased heart rate, contraction of the pupil, con-
stipation, nausea, and vomiting. Opioids can also release his-
tamine from body stores, causing severe itching, hypotension,
sweating, and flushing.
Opioids
85
Overdosing causes stupor and coma. Pulmonary edema
occurs, and froth can be seen coming from the nose and
mouth. An antidote for an opioid overdose is naloxone (Nar-
can®), which can rapidly displace the opioid from the receptor.
Overuse of dextromethorphan can induce euphoria, sedation,
ataxia, increased awareness, sweating, elevated blood pressure,
arrhythmia, hallucinations, and coma. Some of the dextro-
methorphan effects resemble those of phencyclidine.
Opioids induce tolerance, and severe withdrawal signs and
symptoms occur 8 to 12 hours after the last dose. The individual
begins to yawn, and the eyes begin to tear. Sweating, fever,
increased blood pressure and heart rate, piloerection (goose
flesh), dilated pupils, insomnia, chills, gastrointestinal and mus-
cle cramps, nausea, vomiting, and diarrhea may last for 7 to 10
days. Thus, to abruptly stop taking opioids, known as “going cold
turkey,” is a very painful and stressful period for about a week.
Methadone, distributed at medical centers, is cross-tolerant
with morphine and heroin and reduces the withdrawal effects.
Methadone’s effects are long lasting and can be given once daily,
thereby reducing the time spent trying to obtain drug. The dose
of methadone is gradually lowered until the individual no lon-
ger needs any opioid.
FORENSIC ISSUES
A positive urine test result for opioids does not necessarily
mean that the individual used drugs illegally. The GC/MS
instrument is very sensitive, and any morphine detected
could have come from the individual having eaten poppy
seed-containing bagels or pastries shortly before the test.
Also, many people are prescribed opioid-containing analge-
sics such as Tylenol® with codeine, Percodan®, and Percocet®,
and their urine samples will test positive. At the time of urine
86 Forensic Pharmacology
collection, it is important to list the foods or drugs taken in the
prior 24 to 48 hours. Several quinolone antibiotics, including
levofloxacin (Levaquin®) and ofloxacin (Floxin®), can give
false-positive results for opioids in screening procedures.
The initial metabolism of heroin involves loss of one acetyl
group, forming 6-monoacetylmorphine, or 6-MAM. If 6-MAM
is detected in body fluids and tissues, it can only have come
from heroin. When 6-MAM is further metabolized, it loses the
second acetyl group and forms morphine. At this point, finding
morphine, is not helpful in determining whether the individual
had used heroin or morphine, or even codeine, since it also is
metabolized to morphine.
Examples of cases involving opioids include murder, acci-
dental death, positive urine drug test results in child custody
cases, and medical malpractice. In one medical malpractice
case against a physician and a pharmacist, a man who had been
prescribed Tussionex® was found dead. Tussionex® contains
hydrocodone and an antihistamine, chlorpheniramine, and is
used to treat cough, cold, and allergy. At autopsy, blood analysis
revealed the presence of high levels of hydrocodone and also
the benzodiazepines flurazepam and diazepam. Urine analysis
indicated the presence of unchanged cocaine, suggesting use
within the last 8 to 12 hours. All the data led to the conclu-
sion that the deceased had taken an unusually large amount of
Tussionex® that by itself might have been lethal, but that the
combination of hydrocodone and the nonprescribed benzodi-
azepines depressed the CNS and caused death.
SUMMARY
The opioids contain natural and synthetic compounds that are
medicinally used as analgesic, antidiarrheal, and antitussive
agents. Opioids are CNS depre
ssants and decrease blood pres-
Opioids
87
sure, heart rate, and respiration. They can cross the placenta
to affect the fetus. Abuse of opioids can lead to tolerance and
physical dependence. Withdrawal is severe, and several drugs,
based on cross-tolerance, have been used to minimize with-
drawal and to wean the individual off opioids.
9
Hallucinogens
There are two subgroups of hallucinogens: the indolealkyl-
amine derivatives and the phenethylamine derivatives. The
indolealkylamine derivatives, which are related to the neu-
rotransmitter serotonin (5-HT), include lysergic acid diethyl-
amide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), and
bufotenine. The phenethylamine derivatives are related to the
neurotransmitters epinephrine, norepinephrine, and dopamine,
and include mescaline and methylenedioxymethamphetamine
(MDMA, also known as ecstasy). All of the hallucinogens are
Schedule I drugs.
In 1938, at the Sandoz pharmaceutical firm, a Swiss scientist,
Dr. Albert Hofmann, synthesized LSD from lysergic acid, which
is produced by the fungus Claviceps purpurea that infects rye
and other grains. He took the drug himself and was amazed at
the psychosis-mimicking (psychotomimetic) effects. The CIA
secretly tested LSD as a mind-controlling drug, and these experi-
ments resulted in at least one death and led to congressional and
presidential investigations.15 Some street names for LSD include
acid, blotters, California sunshine, Lucy in the sky with diamonds,
panes, paper, pyramids, stamps, sugar, trips, and white lightning.
88
Hallucinogens
89
Psilocybin can be found in over 100 species of mushrooms in
Mexico, Central America, and northwestern and southeastern
parts of the United States. Some of the common mushroom vari-
eties are Psilocybe mexicana, Psilocybe cubensis, Psilocybe azure-scens, and Psilocybe cyanescen. Street names include Alice, magic
mushrooms, purple passion, shrooms, and silly putty.
DMT is found in the South American plants Virola calophylla
and Mimosa hostilis, and in grasses, mushrooms, toads, grubs,
and fish, and has been used by the Amazon natives for spiritual
effects. DMT was synthesized in 1931.
Bufotenine was isolated from skin and parotid gland of the
toad Bufo vulgaris in 1893, and from plants and mushrooms. It
is also found in the toad Bufo marinus that lives in the southern
part of the United States and the Caribbean, and in Bufo alvarius,
found in the southwestern United States. Amazon explorers had
described poisoning by toad and mushroom preparations more
than 400 years ago. Street names include black stone, Chan Su,
Chinese love stones, cohoba, rock hard, Stud 100, and toad.
Mescaline is an alkaloid isolated from the peyote cactus, spe-
cies Lophophora williamsii or Anhalonium lewinii, that grows in the southwestern United States and in Mexico. Mescaline
is found in “buttons” that grow on top of the plant. Aztec and
Native American Indians used the buttons in religious rites and
for treatment of snakebite, flu, and arthritis. Some street names
include bad seed, blue caps, cactus buttons, devils root, mesc,
moon, peyote, shaman, and tops.
Methylenedioxymethamphetamine (MDMA) was synthe-
sized in 1912 and patented in 1914 by Merck as an appetite sup-
pressant, but was never marketed (Figure 9.1). Since the middle
1980s, MDMA, which is primarily known as ecstasy, has become
a popular drug at raves. The final product often contains other
stimulants such as caffeine or cocaine. Users of ecstasy report
enhanced communication and empathy with others. A 2002
90 Forensic Pharmacology
Figure 9.1 MDMA (3,4-methylenedioxymethamphetamine) is a
synthetic drug better known by its street name, ecstasy. It has the
chemical formula C11H15NO2.
NIDA study found that 4.3% of eighth graders, 6.6% of tenth
graders, and 10.5% of twelfth graders used ecstasy at least once.
A 2004 study found that 1.7% of eighth graders, 2.4% of tenth
graders, and 4% of twelfth graders had used ecstasy at least once
in the preceding year. 16
Street names for MDMA, besides ecstasy, include Adam, E,
ecsta eve, Eve, H-bomb (with heroin), hug drug, love drug, M,
pikachu (with PCP), psychedelic amphetamine, Versace, X, and
XTC. Tablets of ecstasy usually have imprinted monograms.
Some examples include E-mail, D&G, Rolex, Nike, Fred Flint-
stone, Pokemon, Batman, and cupid.
PHARMACOLOGY OF HALLUCINOGENS
LSD is the most potent psychoactive drug and is believed to be
3,000 to 4,000 times more potent than mescaline. LSD is used
in tablets (microdots), capsules, sugar cubes, thin squares of
gelatin (window panes), or liquid form, or it is added to absor-
bent paper with various designs that is cut into small squares
Hallucinogens
91
and placed on the tongue (Figure 9.2). It is absorbed rapidly
from the gastrointestinal tract, and effects begin within 5 to
10 minutes. Animal studies indicate that LSD can pass the pla-
centa, but reports of birth defects and chromosomal changes
have not been proven conclusively. The half-life of LSD is about
three hours. LSD can be detected in urine after one to two
hours and for about four days.
Psilocybin mushrooms are chewed or used to make a tea,
or ground into powder. The effects begin approximately 30
Figure 9.2 Acid tabs, shown above, are impregnated with
“acid,” or lysergic acid diethylamide (LSD), a psychedelic drug and
hallucinogen, illegal in most countries but still commonly used for
recreational purposes. LSD is colorless and odorless, and its effects
are unpredictable.
92 Forensic Pharmacology
to 60 minutes later and last for about four hours. It is con-
verted in the liver to psilocin, the biologically active molecule.
Psilocybin and glucuronidated metabolites are detected in
urine within several hours after use and for up to three days
thereafter.
DMT and bufotenine are destroyed in the intestine, and thus
cannot be taken orally. Instead, they are smoked or snorted.
DMT can also be injected, and effects begin in two to five
minutes. The effects last less than 30 minutes, and, because of
its short-acting effects, DMT is known as the “businessman’s
lunch.” Bufotenine’s effects last from 4 to 12 hours.
Mescaline-containing “buttons” on top of the peyote cactus
can be chewed or used to make a tea, or ground into a powder.
Mescaline is absorbed rapidly, and effects begin between one-
half and two hours after ingestion. Its half-life is six hours. Much
of mescaline is excreted unchanged in urine as soon as one hour
after use and for up to four days. In animal studies, there is evi-
dence that mescaline passes into the fetus and can induce mal-
formations. Mescaline, LSD, psilocybin, and DMT all activate
the same serotonin receptor
subtype in the brain.
Ecstasy is taken orally in pill or capsule form, and effects
begin about 45 minutes later and last three to six hours (Figure
9.3). Large amounts of drug can be detected in urine as soon
as one hour after use and for about three days. The half-life
of ecstasy is about eight hours. Ecstasy works on serotonin-
containing neurons. Initially, it leads to an increased release
of serotonin from nerves and inhibits reuptake, resulting
in increased serotonin levels in the synapse. Eventually,
because of depletion and permanent damage to the serotonin
nerve networks, it results in decreased serotonin levels. It
also releases dopamine and norepinephrine. Ecstasy causes
euphoria, an increase in energy, increased communication,
and increased sexual drive. In addition, ecstasy causes teeth
Hallucinogens
93
Figure 9.3 Ecstasy tablets are manufactured in a variety of colors
and are often imprinted with a monogram.
grinding and breakdown of skeletal muscle. Tolerance devel-
ops rapidly.
Effects of hallucinogens can be unpredictable, depending on
the drug and dose, the user’s expectations, and the surround-
ings in which the drug is used. Physiological effects common
to all hallucinogens include dilated pupils; increased heart
rate, blood pressure, and body temperature; sweating; nausea
and vomiting; headache; loss of appetite; sleeplessness; dry
mouth; shaking; speech difficulty; loss of coordination; muscle
rigidity; and visual sensitivity to light. Common psychologi-
cal effects include delusions and hallucinations, including the
94 Forensic Pharmacology
ability to see music and hear colors (an effect called synesthe-
sia). The user’s sense of time and self can change, and he or she
may feel several different emotions all at once or swing rapidly
from one emotion to another, and exhibit impaired concentra-
tion, judgment, and attention. Paranoia, anxiety, confusion,
and depression may develop. Tolerance develops, but not signs
of withdrawal. Cross-tolerance to LSD, mescaline, and psilo-
cybin has been reported. LSD users refer to their experience
as a “trip” and to adverse reactions of terrifying thoughts of
insanity, despair, and death as a “bad trip.” This can last for
several hours. Many LSD users experience “flashbacks,” recur-