Book Read Free

Forensic Pharmacology

Page 6

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

 

‹ Prev