by B Zedeck
sess a written or oral recommendation from their physician.
Medical conditions typically covered by the law include,
but are not limited to, arthritis, anorexia, cancer, chronic
pain, glaucoma, HIV or AIDS, migraine, and multiple scle-
rosis. The California Legislature adopted guidelines in 2003
outlining how much medicinal marijuana patients may grow
and possess. Under the guidelines, patients and/or their
primary caregivers may possess no more than 8 ounces of
dried marijuana and/or 6 mature (or 12 immature) marijuana
plants. However, patients may possess larger amounts if
recommended by a physician.12 Eleven other states have
passed similar laws. On June 6, 2005, the United States
Supreme Court ruled that state laws do not protect against
federal laws banning use of marijuana. The federal govern-
ment, therefore, can stil prosecute sick people using mari-
juana in a state that al ows it. The Supreme Court ruled that
it is up to Congress to change the laws al owing marijuana
use for medical reasons.
50 Forensic Pharmacology
scientists R. Mechoulam and Y. Gaoni reported the isolation and
synthesis of THC.
Marijuana, hashish, hashish oil, and THC are listed in Sched-
ule I. However, marijuana has been used medically as an anti-
emetic agent (an agent that decreases or stops vomiting) for
patients receiving cancer chemotherapy, to decrease intraocu-
lar pressure in patients with glaucoma, as an antispasmodic
for treating multiple sclerosis, and as an appetite-enhancing
drug to diminish wasting in individuals with AIDS. Marinol®
(dronabinol) is a synthetic THC that is taken orally in capsules
containing amounts of THC up to 10 milligrams. It has been
approved for medical use in the United States since 1986 and is
a Schedule III drug.
PHARMACOLOGY OF MARIJUANA
Marijuana is usually smoked in the form of a cigarette (a “joint”)
consisting of chopped-up leaves and stems, or smoked from a
pipe or a water pipe. Much of the THC is destroyed by heat dur-
ing smoking. The effects of THC are felt within minutes and last
from two to five hours.
Marijuana may also be eaten (baked into cookies or brown-
ies), brewed in tea, or swallowed in pill form. Much of oral THC
is destroyed in the stomach, and more is destroyed via first-
pass metabolism. THC is metabolized primarily in the liver
to an active metabolite, 11-hydroxy-THC (11-OH-THC), that
is further converted to the inactive carboxylated compound
11-nor-delta 9-THC-9-COOH (THC-COOH) and its glucuro-
nide form. It is these metabolites that are tested for in urine
samples.
THC is lipid soluble and is released slowly from fatty tissue.
This explains why cannabinoid metabolites may be detected for
3 to 10 days in occasional users and for many weeks in chronic
Cannabinoids
51
users, even after drug use has stopped. Changes in activity or diet
that release fat from fat cells may increase the level of cannabi-
noids detected in urine. THC crosses the placental membranes,
and possible effects on the fetus or infant include a delay in matu-
ration, an alteration of the gestational period, low birth weight,
and behavioral changes. THC is also found in breast milk.
Marijuana acts on cannabinoid receptors found in brain and
peripheral tissues. A natural brain chemical, anandamide, can
also activate the receptors. Marijuana has a range of behav-
ioral effects, including feelings of euphoria, relaxation, mood
changes, panic reactions, and paranoia. It also causes an altered
time perception, lack of concentration, and impairs judgment,
learning, and memory. If alone, a person may become quiet and
drowsy, but if with a group of people, a person may become very
outgoing and laugh easily. Other changes include psychosis,
delusions, and hallucinations. Though controversial, the term
“amotivational syndrome” is used to describe young people
who drop out of social and school activities because of mari-
juana usage.
The physiological effects of marijuana include increased
heart rate, dryness of the mouth and throat, increased appetite,
enlargement of the blood vessels and pupils, sleepiness, decreased
respiration rate, and psychomotor impairment (Figure 5.2).
Ataxia (unsteady balance) and bloodshot eyes are characteristic
of marijuana intoxication. Use of marijuana over a long period of
time can cause lung damage, impairment of cognitive function,
alteration of the immune system, reduced testosterone levels
and enlarged breast tissue in males, and schizophrenia, a mental
disorder that results in disorganized behavior and social with-
drawal. Tolerance does develop, but there is no strong evidence
that marijuana causes physical dependence. Stopping marijuana
after prolonged use, however, can lead to restlessness, irritability,
insomnia, nausea, anxiety, depression, and anorexia.
52 Forensic Pharmacology
Figure 5.2 A close-up of a human eye with a dilated pupil is shown in
the photograph above. Dilation of the pupil (mydriasis) occurs in response
to release of adrenaline in the body (the fight-or-flight response) or the
use of drugs such as amphetamine or marijuana.
FORENSIC ISSUES
Hemp seed oil, legally sold in the United States, is a source for
essential omega fatty acids. This product is made from steril-
ized seeds that cannot grow new marijuana plants. Although
the small amount of marijuana present cannot exert a euphoric
effect, sufficient amounts of THC metabolites are produced and
can be detected in urine. A positive result can be explained away
if it can be proven that the individual had used hemp seed oil.
Hemp seeds are also being used in a variety of foods such as
chips and granola. Another complication in drug testing arises
Cannabinoids 53
with the issue of secondhand smoke. Under certain conditions,
inhalation of secondhand smoke contains sufficient amounts of
THC to register positive on a urine drug test.
Seized samples of marijuana are analyzed in the laboratory
using a color test, thin-layer chromatography, and a microscopic
test. The Duquenois-Levine color test, although not specific for
marijuana, is often used. Using the microscope one can see on
the upper side of the marijuana leaf characteristic “bear claw”-
shaped cystolithic hairs, which contain calcium carbonate.
In driving-related court cases, it is often difficult to prove
impairment, since even if the marijuana was used hours or days
earlier, the metabolites are still being released from fat cells and
excreted in urine. Defense arguments in cases with positive
random urine tests include use of hemp seed oil, unknowingly
ingesting marijuana-laced foods, or exposure to secondhand
smoke. The latter argument is very dependent on the concentra-
tion of metabolite in urine.
In one particular case, a motorcyclist hit a car and was
severely injured. At the hospital, approximately one hour after
the accident, the cyclist’s blood alcohol content (BAC) was
0.021%. Back extrapolation (see Chapter 7) to the time of the
accident could increase that value to 0.036%. His urine tests
revealed use of cocaine and marijuana. Marijuana metabolites
were confirmed by gas chromatography/mass spectrometry
(GC/MS). All these results were used to try and prove that the
cyclist was impaired. However, the presence of drug in urine
is not a good indicator of drug concentration in blood or of
impairment at the time of the accident, and the BAC was prob-
ably too low to cause impairment. At best, one could say that
the cyclist does use drugs and uses several of them at the same
time, but use of the drugs may not have played a role in causing
the accident. The case was settled.
54 Forensic Pharmacology
SUMMARY
The active ingredient in marijuana is delta-9-tetrahydrocan-
nabinol (THC). Marijuana may be smoked or ingested. THC is
stored in fatty tissue, from which it is released slowly. THC can
induce many behavioral and physiological changes, some depen-
dent on the social setting. Chronic use can lead to serious effects
on the endocrine, respiratory, immune, and nervous systems.
Use of marijuana during pregnancy may lead to abnormal fetal
development. Although tolerance to THC can develop, there is
no strong evidence of physical dependence. THC is being used
for medical purposes, and such use has sparked debate between
law enforcement and the medical community.
Central
Nervous System
Stimulants
6
This chapter will focus on cocaine, amphetamine, methamphet-
amine, cathinone and methcathinone, and ephedrine—just a
few of the many central nervous system (CNS) stimulants.
COCAINE
Cocaine, a Schedule II drug, is found in the leaf of the coca plant
growing mostly in the Andean region of South America. The
two main plant species are Erythroxylum coca and Erythroxylum
novogranatense. The Indians of Peru used coca plant leaves for
thousands of years as part of religious ceremonies and knew of
its ability to abolish hunger and decrease fatigue. Cocaine was
isolated from the plant in 1859 by the German chemist Albert
Niemann (Figure 6.1). In 1863, it became popular as a compo-
nent of the French wine, Vin Mariani, sold for its restorative
and tonic properties. In 1884, Sigmund Freud wrote a paper
about the effects of cocaine and described its ability to enhance
elation, physical endurance, and mental agility. Also in 1884,
the medical community learned of cocaine’s local anesthetic
properties. In 1886, in the United States, a pharmacist named
55
56 Forensic Pharmacology
John Styth Pemberton prepared a drink containing extract of
coca leaf and caffeine that he termed Coca-Cola. Today, because
of drug laws enacted in the early 1900s, coca extract is still used
to prepare Coca-Cola, but the cocaine is removed. Cocaine is
used medicinally as a local anesthetic, applied topically by some
surgeons for nasal, throat, and ear surgery.
Cocaine is found in several forms. It can be extracted from the
coca leaf to form coca paste (basuco, pitillo), which is not water
soluble but can be smoked. The paste can be further treated to
form cocaine hydrochloride (cocaine powder), which can be dis-
solved in water and injected, or can be snorted into the nostril.
Freebase cocaine and crack cocaine, each containing cocaine
base, are prepared from cocaine hydrochloride by adding ammo-
nia and ether or sodium bicarbonate and heat, respectively.
Applying heat to evaporate the ether can cause the ether to ignite,
which can cause severe burns. In preparing crack cocaine, the
Figure 6.1 Cocaine is obtained from the leaves of the coca plant. It
has a chemical formula of C17H21NO4.
Central Nervous System Stimulants
57
mixture is allowed to dry into a cake that is cut into little pieces.
Cocaine, used as freebase or crack, is not water soluble and is
smoked. When smoking the small crack pieces, carbon dioxide
is released and makes a crackling sound, hence, the name crack.
Any form of cocaine base is easily differentiated from cocaine
hydrochloride using infrared spectrometry.
Some street names for cocaine include blow, C, Charlie, coke,
crack, dynamite, happy dust, nose candy, rock, snow, snuff,
stardust, toot, and white lady. The combination of cocaine and
heroin is termed speedball.
AMPHETAMINE AND RELATED DRUGS
Amphetamine, a Schedule II drug, was synthesized by the Ger-
man chemist L. Edeleano in 1887 (Figure 6.2). The trade names for
amphetamine are Benzedrine and Dexedrine. Smith, Kline, and
French marketed Benzedrine inhaler in the 1930s for respiratory
disorders. Since amphetamine decreases drowsiness and fatigue,
it is marketed for narcolepsy and attention-deficit/hyperactivity
disorder (ADHD), and was used as an appetite suppressant
(anorectic) in diet regimens. Amphetamine was supplied to the
Figure 6.2 Methamphetamine (right) is created by adding a methyl
group (CH3) to amphetamine (left).
58 Forensic Pharmacology
soldiers during World War II to overcome fatigue, and to avia-
tors in the Persian Gulf War. Recently, baseball has banned use
of amphetamines. Street names for amphetamine include amp,
black beauties, crosses, crystal, dexies, pep pills, speed, truck
drivers, and uppers.
Methamphetamine, a Schedule II drug, was first synthe-
sized in 1919. It can be synthesized from ephedrine or pseudo-
ephedrine. Methamphetamine is available by prescription for
weight control, ADHD, and narcolepsy under the brand name
Desoxyn®. Street names for methamphetamine include chalk,
crank, crystal, fire, glass, ice, rocks, shabu, speed, and yaba.
Methamphetamine is often found at rave sites, where people
exert themselves while dancing and deprive themselves of sleep,
food, and drink, which can result in increased body temperature
with excessive sweating and possibly a salt imbalance.
Cathinone is isolated from the leaves of khat, Catha edulis, a
plant that grows in East Africa, Southern Arabia, and the Middle
East, as well as in the desert areas of the southern United States
(Figure 6.3). Cathinone has been used since the thirteenth cen-
tury, when it was given to soldiers to relieve fatigue. The youngest
leaves at the top of the plant are preferred. As the leaves dry, cathi-
none, which is structurally related to ephedrine and amphet-
amine, is converted to the less potent cathine. The synthesis of
methcathinone, more potent than cathinone, became popular in
Russia and was brought to the United States in the early 1990s.
Methcathinone is easy to synthesize from ephedrine. Cathinone
and methcathinone are Schedule I drugs, and cathine is a Sched-
ule IV drug. S
treet names for khat (cathinone) include Abyssin-
ian tea, African salad, chat, kat, qat, and shat. Methcathinone is
known as bathtub speed, cadillac express, cat, gagers, go-fast,
and wild cat.
Ephedrine is found in the ephedra plant ( Ephedra sinica—
the Chinese herb Ma Huang). It is used as a nasal decongestant
Central Nervous System Stimulants
59
Figure 6.3 Above, khat stems have been wrapped in banana
leaves to preserve their freshness. Khat is a plant native to Africa,
whose stems and leaves are chewed for their euphoric, stimulant
effect.
60 Forensic Pharmacology
and bronchodilator in asthmatic patients and was once used
in weight control programs. Its analog, pseudoephedrine, can
be found in many cold remedy products including Comtrex®,
Sudafed®, Benadryl-D®, Drixoral®, Claritin-D®, Tylenol®
Sinus, and Vicks DayQuil® Sinus. Ephedrine is metabolized
to phenylpropanolamine, and both ephedrine and phenylpro-
panolamine have been removed from the over-the-counter
market because of apparent increases in blood pressure leading
to strokes.
PHARMACOLOGY OF CNS STIMULANTS
Depending on the drug and its form, CNS stimulants are usually
taken either orally as a solid or tea or by the chewing of leaves,
by injection, by smoking, or by snorting. Injection directly into
the bloodstream or inhalation of smoke into the lungs induces a
very rapid onset of action. CNS stimulants induce their effects by
increasing the synaptic concentrations of several neurotransmit-
ters, particularly norepinephrine (noradrenaline), dopamine,
and serotonin. They stimulate the release of neurotransmitters
and block their reuptake.
Cocaine
Cocaine is a local vasoconstrictor, and snorting of cocaine intra-
nasally reduces the amount of blood flow to the area, resulting
in a reduced rate of drug absorption and slower onset of action.
Often in cocaine abusers, the reduced blood supply to the nasal
septum leads to the development of a perforation between the
nasal passages. The effects of cocaine last approximately 40
minutes, while the effects of other stimulants usually last several
hours, as each has a different half-life.
One of the primary metabolites of cocaine is the inactive
benzoylecgonine. Cocaine, but not benzoylecgonine, passes
Central Nervous System Stimulants